The Scientific World Journal: Genetics The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Antimutagenic Effect of Hibiscus sabdariffa L. Aqueous Extract on Rats Treated with Monosodium Glutamate Thu, 19 Jan 2017 00:00:00 +0000 Hibiscus sabdariffa L. is a plant of the Malvaceae family, commonly known as roselle. H. sabdariffa is known to contain antioxidant, cholesterol-lowering, antiobesity, insulin resistance reduction, antihypertensive, and skin cancer chemopreventive properties. This study evaluated the effects of H. sabdariffa aqueous extract against cyclophosphamide (CPA, 25 mg/Kg) induced damage to DNA in male Wistar rats by micronucleus test. Samples of H. sabdariffa calyx were obtained in the municipality of Barra do Garças, Mato Grosso, Brazil. The aqueous extract was prepared by infusion and each animal received a daily dose of 400 mg/Kg by gavage for 15 consecutive days of treatment. The presence of anthocyanins was confirmed by ferric chloride test and phenolic compounds using high-performance liquid chromatography, with emphasis on the identification of rutin. The animals were sacrificed by deepening of anaesthesia to obtain bone marrow and determination of the frequency of micronucleated polychromatic erythrocytes. The group treated with the aqueous extract of H. sabdariffa revealed a 91% reduction in micronucleus frequency when compared with the positive control group. Under the conditions tested, H. sabdariffa L. presented a protective effect to CPA-induced damage to DNA of the treated animals, and it is a potential candidate as a chemopreventive agent against carcinogenesis. Ana Carla Guidini Valentini Gheller, Jacqueline Kerkhoff, Gerardo Magela Vieira Júnior, Kleber Eduardo de Campos, and Marina Mariko Sugui Copyright © 2017 Ana Carla Guidini Valentini Gheller et al. All rights reserved. Psychomotor Development in Cri du Chat Syndrome: Comparison in Two Italian Cohorts with Different Rehabilitation Methods Mon, 28 Nov 2016 11:21:22 +0000 The Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5 (5p−). It is well known that home-reared patients show better performances as compared to institutionalised cases, and it was reported that continuous educational intervention can ameliorate their performances. To assess the efficacy of educational intervention and to develop new CdC oriented programs of rehabilitation, we compare the results obtained for many developmental skills in two groups of CdC patients undergoing two different rehabilitation programs. Using data on the development of a group of CdC patients obtained by validated Italian translation for the Denver Developmental Screening Test II, we compared a group of 13 patients undergoing an educational program developed for CdC patients, the Mayer Project (MP), with a second group of 15 cases in whom caring was not specifically oriented. A positive impact of the MP was reported by parents, observing an improvement in social skills obtained, even if no significant differences were observed when the items of the Denver Test are studied. The need for personalized care in CdC patients and the choice of different methods to compare the results are also discussed. Andrea Guala, Marianna Spunton, Fabio Tognon, Marilena Pedrinazzi, Luisa Medolago, Paola Cerutti Mainardi, Silvia Spairani, Michela Malacarne, Enrico Finale, Mario Comelli, and Cesare Danesino Copyright © 2016 Andrea Guala et al. All rights reserved. Molecular Identification and Traceability of Illegal Trading in Lignobrycon myersi (Teleostei: Characiformes), a Threatened Brazilian Fish Species, Using DNA Barcode Wed, 07 Sep 2016 13:27:13 +0000 Lignobrycon myersi is a threatened freshwater fish species and endemic of a few coastal rivers in northeastern Brazil. Even though the Brazilian laws prohibit the fisheries of threatened species, L. myersi is occasionally found in street markets, being highly appreciated by local population. In order to provide a reliable DNA barcode dataset for L. myersi, we compared mitochondrial sequences of cytochrome c oxidase subunit I (COI) from fresh, frozen, and salt-preserved specimens. Phylogenetically related species (Triportheus spp.) and other fish species (Astyanax fasciatus) commonly mixed with L. myersi in street markets were also included to test the efficiency of molecular identification. In spite of the differences in conservation processes and advanced deterioration of some commercial samples, high-quality COI sequences were obtained and effective in discriminating L. myersi specimens. In addition, while populations from Contas and Almada River basins seem to comprise a single evolutionary lineage, the specimens from Cachoeira River were genetically differentiated, indicating population structuring. Therefore, DNA barcoding has proved to be useful to trace the illegal trading of L. myersi and to manage threatened populations, which should focus on conservation of distinct genetic stocks and mitigation on human impacts along their range. Alexandre dos Santos Rodrigues, José Henrique Souza Galdino Brandão, Jamille de Araújo Bitencourt, Ricardo Jucá-Chagas, Iracilda Sampaio, Horácio Schneider, and Paulo Roberto Antunes de Mello Affonso Copyright © 2016 Alexandre dos Santos Rodrigues et al. All rights reserved. Retracted: Flavonoid-Deficient Mutants in Grass Pea (Lathyrus sativus L.): Genetic Control, Linkage Relationships, and Mapping with Aconitase and S-Nitrosoglutathione Reductase Isozyme Loci Thu, 01 Sep 2016 08:47:43 +0000 The Scientific World Journal Copyright © 2016 The Scientific World Journal. All rights reserved. Variability Assessment of Aromatic and Fine Rice Germplasm in Bangladesh Based on Quantitative Traits Thu, 31 Mar 2016 11:22:02 +0000 The study was conducted to investigate genetic variability among 113 aromatic and fine local rice genotypes of which five were exotic in origin. The test genotypes were evaluated for 19 growth traits, yield components, and yield. All the quantitative traits varied significantly among the test genotypes. High heritability along with high genetic advance was observed for flag leaf area, secondary branches per panicle, filled grains per panicle, grain length, grain breadth, grain length breadth ratio, and 1000 grain weight. Such findings suggested preponderance of additive gene action in gene expression for these characters. Grain yield was significantly and positively correlated with days to flowering, days to maturity, panicle length, filled grains per panicle, and 1000 grain weight. According to cluster analysis, 113 test genotypes formed 10 clusters. Selection of parents from the clusters V and X followed by hybridization would possibly result in desirable heterosis for the development of heterotic rice hybrids. Finally, molecular characterizations of the studied germplasm are required for high resolution QTL mapping and validating the presence of candidate genes responsible for valuable characters. M. Z. Islam, M. Khalequzzaman, M. K. Bashar, N. A. Ivy, M. M. Haque, and M. A. K. Mian Copyright © 2016 M. Z. Islam et al. All rights reserved. Inferring Diversity and Evolution in Fish by Means of Integrative Molecular Cytogenetics Sun, 09 Aug 2015 12:57:46 +0000 Fish constitute a paraphyletic and profusely diversified group that has historically puzzled ichthyologists. Hard efforts are necessary to better understand this group, due to its extensive diversity. New species are often identified and it leads to questions about their phylogenetic aspects. Cytogenetics is becoming an important biodiversity-detection tool also used to measure biodiversity evolutionary aspects. Molecular cytogenetics by fluorescence in situ hybridization (FISH) allowed integrating quantitative and qualitative data from DNA sequences and their physical location in chromosomes and genomes. Although there is no intention on presenting a broader review, the current study presents some evidences on the need of integrating molecular cytogenetic data to other evolutionary biology tools to more precisely infer cryptic species detection, population structuring in marine environments, intra- and interspecific karyoevolutionary aspects of freshwater groups, evolutionary dynamics of marine fish chromosomes, and the origin and differentiation of sexual and B chromosomes. The new cytogenetic field, called cytogenomics, is spreading due to its capacity to give resolute answers to countless questions that cannot be answered by traditional methodologies. Indeed, the association between chromosomal markers and DNA sequencing as well as between biological diversity analysis methodologies and phylogenetics triggers the will to search for answers about fish evolutionary, taxonomic, and structural features. Roberto Ferreira Artoni, Jonathan Pena Castro, Uedson Pereira Jacobina, Paulo Augusto Lima-Filho, Gideão Wagner Werneck Félix da Costa, and Wagner Franco Molina Copyright © 2015 Roberto Ferreira Artoni et al. All rights reserved. First Report of CTNS Mutations in a Chinese Family with Infantile Cystinosis Tue, 17 Mar 2015 13:38:26 +0000 Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a prototype for lysosomal transport disorders. To date, several CTNS mutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, the CTNS mutation is very rarely reported. For the Chinese population, no literature on CTNS mutation screening for IC is available to date. In this paper, by using the whole exome sequencing and Sanger sequencing, we identified two novel CTNS splicing deletions in a Chinese IC family, one at the donor site of exon 6 of CTNS (IVS6+1, del G) and the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give information for the genetic counseling of the IC that occurred in Chinese population. Yong-jia Yang, Yuan Hu, Rui Zhao, Xinyu He, Liu Zhao, Ming Tu, Lijun Zhou, Jihong Guo, Linqian Wu, Tantai Zhao, and Yi-min Zhu Copyright © 2015 Yong-jia Yang et al. All rights reserved. Association between Polymorphism of Interleukin-1beta and Interleukin-1 Receptor Antagonist Gene and Asthma Risk: A Meta-Analysis Mon, 02 Mar 2015 17:07:45 +0000 Background. Asthma is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the polymorphism of IL-1β -511C/T and IL-1RA genes in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Accordingly, we conducted a comprehensive meta-analysis to investigate the association between the IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Methods. Data were collected from the following electronic databases: Pub Med, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), ISI Web of Knowledge, and Google Scholar Search databases with the last report up to July 2013. Finally, 15 studies were included in our meta-analysis. We summarized the data on the association between IL-1β -511C/T and IL-1RA polymorphism and risk of asthma in the overall population and performed subgroup analyses by ethnicity, mean of age, and source of controls. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Statistical analysis was performed with Review Manager 5.1. Results. A total of 15 case-control studies were included in the meta-analysis of IL-1β -511C/T (1,385 cases and 1,964 controls) and IL-1RA (2,800 cases and 6,359 controls) genotypes. No association was found between IL-1β -511C/T polymorphism and asthma risk (dominant model: , 95% CI: 0.99–1.25, , ; recessive model: , 95% CI: 0.91–1.20, , ). Subgroup analysis based on ethnicity (Asian and Caucasian), source of controls (population-based controls and hospital-based controls), and mean of age (adulthood and childhood) did not present any significant association. The overall results showed that the IL-1RA polymorphism was related to an increased risk of asthma (homozygote model: , 95% CI: 1.12–1.56, , ; recessive model: , 95% CI: 1.18–1.63, , ). Similar results were found in the subgroup analyses by ethnicity, mean of age, and source of controls. Sensitivity analysis did not perturb the results. Conclusions. This meta-analysis provided strong evidence that the IL-1RA polymorphism was a risk factor of asthma, especially in Caucasian populations. However, no association was found for IL-1β -511C/T genotype carriers. Larger scale studies are needed for confirmation. Yuanzhou He, Shuang Peng, Weining Xiong, Yongjian Xu, and Jin Liu Copyright © 2015 Yuanzhou He et al. All rights reserved. Genetic and Biochemical Diversity among Valeriana jatamansi Populations from Himachal Pradesh Sun, 08 Feb 2015 09:22:10 +0000 Valeriana jatamansi Jones is an important medicinal plant that grows wild in Himachal Pradesh, India. Molecular and biochemical diversity among 13 natural populations from Himachal Pradesh was assessed using RAPD and GC-MS to know the extent of existing variation. A total of seven genetically diverse groups have been identified based on RAPD analysis which corroborated well with the analysis based on chemical constituents. The essential oil yield ranged from 0.6% to 1.66% (v/w). A negative correlation between patchouli alcohol and viridiflorol, the two major valued constituents, limits the scope of their simultaneous improvement. However, other few populations like Chamba-II and Kandi-I were found promising for viridiflorol and patchouli alcohol, respectively. The analysis of chemical constitution of oil of the populations from a specific region revealed predominance of specific constituents indicating possibility of their collection/selection for specific end uses like phytomedicines. The prevalence of genetically diverse groups along with sufficient chemical diversity in a defined region clearly indicates the role of ecology in the maintenance of evolution of this species. Sufficient molecular and biochemical diversity detected among natural populations of this species will form basis for the future improvement. Sunil Kumar Singh, Rajan Katoch, and Rakesh Kumar Kapila Copyright © 2015 Sunil Kumar Singh et al. All rights reserved. Use of Selected Essential Oils to Control Aflatoxin Contaminated Stored Cashew and Detection of Aflatoxin Biosynthesis Gene Sun, 18 Jan 2015 06:20:26 +0000 Aspergillus spp. associated with cashew from the regions of Riyadh, Dammam, and Abha were isolated and three different culture media were used to qualitatively measure aflatoxin production by Aspergillus via UV light (365 nm), which was expressed as positive or negative. The obtained data showed that six isolates of A. flavus and four isolates of A. parasiticus were positive for aflatoxin production, while all isolates of A. niger were negative. Five commercially essential oils (thyme, garlic, cinnamon, mint, and rosemary) were tested to determine their influence on growth and aflatoxin production in A. flavus and A. parasiticus by performing high-performance liquid chromatography (HPLC). The results showed that the tested essential oils caused highly significant inhibition of fungal growth and aflatoxin production in A. flavus and A. parasiticus. The extent of the inhibition of fungal growth and aflatoxin production was dependent on the type and concentration of essential oils applied. The results indicate that cinnamon and thyme oils show strong antimicrobial potential. PCR was used with four sets of primer pairs for nor-1, omt-1, ver-1, and aflR genes, enclosed in the aflatoxin biosynthetic pathway. The interpretation of the results revealed that PCR is a rapid and sensitive method. Abeer R. M. Abd El-Aziz, Mohamed A. Mahmoud, Monira R. Al-Othman, and Munirah F. Al-Gahtani Copyright © 2015 Abeer R. M. Abd El-Aziz et al. All rights reserved. The Alpaca Melanocortin 1 Receptor: Gene Mutations, Transcripts, and Relative Levels of Expression in Ventral Skin Biopsies Mon, 05 Jan 2015 07:31:10 +0000 The objectives of the present study were to characterize the MC1R gene, its transcripts and the single nucleotide polymorphisms (SNPs) associated with coat color in alpaca. Full length cDNA amplification revealed the presence of two transcripts, named as F1 and F2, differing only in the length of their 5′-terminal untranslated region (UTR) sequences and presenting a color specific expression. Whereas the F1 transcript was common to white and colored (black and brown) alpaca phenotypes, the shorter F2 transcript was specific to white alpaca. Further sequencing of the MC1R gene in white and colored alpaca identified a total of twelve SNPs; among those nine (four silent mutations (c.126C>A, c.354T>C, c.618G>A, and c.933G>A); five missense mutations (c.82A>G, c.92C>T, c.259A>G, c.376A>G, and c.901C>T)) were observed in coding region and three in the 3′UTR. A 4 bp deletion (c.224 227del) was also identified in the coding region. Molecular segregation analysis uncovered that the combinatory mutations in the MC1R locus could cause eumelanin and pheomelanin synthesis in alpaca. Overall, our data refine what is known about the MC1R gene and provides additional information on its role in alpaca pigmentation. Bathrachalam Chandramohan, Carlo Renieri, Vincenzo La Manna, and Antonietta La Terza Copyright © 2015 Bathrachalam Chandramohan et al. All rights reserved. Effect of Nitrogen Source and Inorganic Phosphate Concentration on Methanol Utilization and PEX Genes Expression in Pichia pastoris Wed, 24 Dec 2014 00:10:18 +0000 Methylotrophic yeast Pichia pastoris has proved to be especially useful for production of various heterologous proteins. In biotechnology it is very important to maintain the balance between high levels of heterologous gene expression and cell viability. Decisive understanding of gene regulation mechanisms is essential for reaching this goal. In this study, we investigated the effect of different nitrogen sources and phosphate concentration in media on methanol utilization. It was shown that expression levels of main genes, which are involved in methanol utilization (MUT genes) and in functioning of peroxisomes (PEX genes), are maximal when ammonium sulphate is used as a nitrogen source. Expression of these genes is decreased in media with poor nitrogen sources, such as proline. Addition of rapamycin to the media completely removed repression of AOX1 promoter in media with proline, which allows proposing that Tor-kinase is involved in establishing of nitrogen regulation of this gene. It was also shown that MUT genes expression levels get higher, when the phosphate concentration in media is increased. A. M. Rumjantsev, O. V. Bondareva, M. V. Padkina, and E. V. Sambuk Copyright © 2014 A. M. Rumjantsev et al. All rights reserved. Inheritance of Nitrogen Use Efficiency in Inbred Progenies of Tropical Maize Based on Multivariate Diallel Analysis Sun, 21 Dec 2014 06:13:19 +0000 The objective of our study was to characterize and determine the patterns of genetic control in relation to tolerance and efficiency of nitrogen use by means of a complete diallel cross involving contrasting inbred progenies of tropical maize based on a univariate approach within the perspective of a multivariate mixed model. Eleven progenies, previously classified regarding the tolerance and responsiveness to nitrogen, were crossed in a complete diallel cross. Fifty-five hybrids were obtained. The hybrids and the progenies were evaluated at two different nitrogen levels, in two locations. The grain yield was measured as well as its yield components. The heritability values between the higher and lower nitrogen input environment did not differ among themselves. It was observed that the general combining ability values were similar for both approaches univariate and multivariate, when it was analyzed within each location and nitrogen level. The estimate of variance of the specific combining ability was higher than general combining ability estimate and the ratio between them was 0.54. The univariate and multivariate approaches are equivalent in experiments with good precision and high heritability. The nonadditive genetic effects exhibit greater quantities than the additive genetic effects for the genetic control of nitrogen use efficiency. Fernando Lisboa Guedes, Rafael Parreira Diniz, Marcio Balestre, Camila Bastos Ribeiro, Renato Barbosa Camargos, and João Cândido Souza Copyright © 2014 Fernando Lisboa Guedes et al. All rights reserved. Physical Mapping of the 5S and 18S rDNA in Ten Species of Hypostomus Lacépède 1803 (Siluriformes: Loricariidae): Evolutionary Tendencies in the Genus Mon, 27 Oct 2014 09:29:26 +0000 Hypostomus is a diverse group with unclear aspects regarding its biology, including the mechanisms that led to chromosome diversification within the group. Fluorescence in situ hybridization (FISH) with 5S and 18S rDNA probes was performed on ten Hypostomini species. Hypostomus faveolus, H. cochliodon, H. albopunctatus, H. aff. paulinus, and H. topavae had only one chromosome pair with 18S rDNA sites, while H. ancistroides, H. commersoni, H. hermanni, H. regani, and H. strigaticeps had multiple 18S rDNA sites. Regarding the 5S rDNA genes, H. ancistroides, H. regani, H. albopunctatus, H. aff. paulinus, and H. topavae had 5S rDNA sites on only one chromosome pair and H. faveolus, H. cochliodon, H. commersoni, H. hermanni, and H. strigaticeps had multiple 5S rDNA sites. Most species had 18S rDNA sites in the telomeric region of the chromosomes. All species but H. cochliodon had 5S rDNA in the centromeric/pericentromeric region of one metacentric pair. Obtained results are discussed based on existent phylogenies for the genus, with comments on possible dispersion mechanisms to justify the variability of the rDNA sites in Hypostomus. Vanessa Bueno, Paulo César Venere, Jocicléia Thums Konerat, Cláudio Henrique Zawadzki, Marcelo Ricardo Vicari, and Vladimir Pavan Margarido Copyright © 2014 Vanessa Bueno et al. All rights reserved. A Premature Termination of Human Epidermal Growth Factor Receptor Transcription in Escherichia coli Wed, 15 Oct 2014 07:14:22 +0000 Our success in producing an active epidermal growth factor receptor (EGFR) tyrosine kinase in Escherichia coli encouraged us to express the full-length receptor in the same host. Despite its large size, we were successful at producing the full-length EGFR protein fused to glutathione S-transferase (GST) that was detected by Western blot analysis. Moreover, we obtained a majoritarian truncated GST-EGFR form detectable by gel electrophoresis and Western blot. This truncated protein was purified and confirmed by MALDI-TOF/TOF analysis to belong to the N-terminal extracellular region of the EGFR fused to GST. Northern blot analysis showed two transcripts suggesting the occurrence of a transcriptional arrest. Jihene Elloumi-Mseddi, Karim Jellali, Antonio Villalobo, and Sami Aifa Copyright © 2014 Jihene Elloumi-Mseddi et al. All rights reserved. Sequential Steps of Chromosomal Differentiation in Atlantic Surgeonfishes: Evolutionary Inferences Tue, 12 Aug 2014 07:09:42 +0000 Surgeonfishes are a species-rich group and a major biomass on coral reefs. Three species are commonly found throughout South Atlantic, Acanthurus bahianus, A. chirurgus, and A. coeruleus. In this paper, we present the first cytogenetic data of these species, revealing a sequential chromosomal diversification. A. coeruleus was characterized by a relatively conserved karyotype evolved by pericentric inversions of some pairs (, 2sm + 4st + 42a). In contrast, the karyotypes of A. bahianus () and A. chirurgus () were highly differentiated by the presence of six large metacentric pairs in A. bahianus (12m + 2sm + 4st + 18a) and A. chirurgus (12m + 2sm + 4st +1 6a) probably derived by chromosomal fusions that corroborate their closer relationship. A discernible in tandem fusion represents an autapomorphic character to A. chirurgus. In spite of macrostructure variation, single nucleolar organizer regions (NORs) on short arms of a subtelocentric pair and similar distribution of C-bands were observed in the three species. Overlapping of chromosomal data with molecular phylogeny indicated pericentric inversions which took place nearly at 19 Ma while centric fusions are as recent as 5 Ma. A physical mapping of coding and noncoding sequences in Acanthurus could clarify the role of additional rearrangements during their chromosomal evolution. Paulo Roberto Antunes de Mello Affonso, Maria Aparecida Fernandes, Josivanda Santos Almeida, and Wagner Franco Molina Copyright © 2014 Paulo Roberto Antunes de Mello Affonso et al. All rights reserved. VEGF Genetic Polymorphisms May Contribute to the Risk of Diabetic Nephropathy in Patients with Diabetes Mellitus: A Meta-Analysis Mon, 11 Aug 2014 12:15:11 +0000 Objective. This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). Methods. We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. Results. Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. Conclusion. Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients. Li Sun, Quan Yuan, Ning Cao, Wei Guo, Li Yao, Jiang-Min Feng, Jian-Fei Ma, and Li-Ning Wang Copyright © 2014 Li Sun et al. All rights reserved. Genome Wide Analysis of Sex Difference in Gene Expression Profiles of Bone Formations Using sfx Mice and BXD RI Strains Mon, 14 Jul 2014 08:27:44 +0000 The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference. Yue Huang, Xiaodong Zhu, Lishi Wang, Xiaoyun Liu, Lu Lu, Weikuan Gu, and Yan Jiao Copyright © 2014 Yue Huang et al. All rights reserved. Prediction of Maize Single Cross Hybrids Using the Total Effects of Associated Markers Approach Assessed by Cross-Validation and Regional Trials Thu, 03 Jul 2014 07:40:27 +0000 The present study aimed to predict the performance of maize hybrids and assess whether the total effects of associated markers (TEAM) method can correctly predict hybrids using cross-validation and regional trials. The training was performed in 7 locations of Southern Brazil during the 2010/11 harvest. The regional assays were conducted in 6 different South Brazilian locations during the 2011/12 harvest. In the training trial, 51 lines from different backgrounds were used to create 58 single cross hybrids. Seventy-nine microsatellite markers were used to genotype these 51 lines. In the cross-validation method the predictive accuracy ranged from 0.10 to 0.96, depending on the sample size. Furthermore, the accuracy was 0.30 when the values of hybrids that were not used in the training population (119) were predicted for the regional assays. Regarding selective loss, the TEAM method correctly predicted 50% of the hybrids selected in the regional assays. There was also loss in only 33% of cases; that is, only 33% of the materials predicted to be good in training trial were considered to be bad in regional assays. Our results show that the predictive validation of different crop conditions is possible, and the cross-validation results strikingly represented the field performance. Wagner Mateus Costa Melo, Renzo Garcia Von Pinho, and Marcio Balestre Copyright © 2014 Wagner Mateus Costa Melo et al. All rights reserved. Molecular Identification of Necrophagous Muscidae and Sarcophagidae Fly Species Collected in Korea by Mitochondrial Cytochrome c Oxidase Subunit I Nucleotide Sequences Wed, 28 May 2014 07:07:41 +0000 Identification of insect species is an important task in forensic entomology. For more convenient species identification, the nucleotide sequences of cytochrome c oxidase subunit I (COI) gene have been widely utilized. We analyzed full-length COI nucleotide sequences of 10 Muscidae and 6 Sarcophagidae fly species collected in Korea. After DNA extraction from collected flies, PCR amplification and automatic sequencing of the whole COI sequence were performed. Obtained sequences were analyzed for a phylogenetic tree and a distance matrix. Our data showed very low intraspecific sequence distances and species-level monophylies. However, sequence comparison with previously reported sequences revealed a few inconsistencies or paraphylies requiring further investigation. To the best of our knowledge, this study is the first report of COI nucleotide sequences from Hydrotaea occulta, Muscina angustifrons, Muscina pascuorum, Ophyra leucostoma, Sarcophaga haemorrhoidalis, Sarcophaga harpax, and Phaonia aureola. Yu-Hoon Kim, Sang Eon Shin, Chan Seon Ham, Seong Yoon Kim, Kwang Soo Ko, Tae-Ho Jo, Gi Hoon Son, Seong Hwan Park, and Juck-Joon Hwang Copyright © 2014 Yu-Hoon Kim et al. All rights reserved. A New Subspecies Identification and Population Study of the Asian Small-Clawed Otter (Aonyx cinereus) in Malay Peninsula and Southern Thailand Based on Fecal DNA Method Thu, 13 Mar 2014 09:54:30 +0000 Three species of otter can be found throughout Malay Peninsula: Aonyx cinereus, Lutra sumatrana, and Lutrogale perspicillata. In this study, we focused on the A. cinereus population that ranges from the southern and the east coast to the northern regions of Malay Peninsula up to southern Thailand to review the relationships between the populations based on the mitochondrial D-loop region. Forty-eight samples from six populations were recognized as Johor, Perak, Terengganu, Kelantan, Ranong, and Thale Noi. Among the 48 samples, 33 were identified as A. cinereus, seven as L. sumatrana, and eight as L. perspicillata. Phylogenetically, two subclades formed for A. cinereus. The first subclade grouped all Malay Peninsula samples except for samples from Kelantan, and the second subclade grouped Kelantan samples with Thai sample. Genetic distance analysis supported the close relationships between Thai and Kelantan samples compared to the samples from Terengganu and the other Malaysian states. A minimum-spanning network showed that Kelantan and Thailand formed a haplogroup distinct from the other populations. Our results show that Thai subspecies A. cinereus may have migrated to Kelantan from Thai mainland. We also suggest the classification of a new subspecies from Malay Peninsula, the small-clawed otter named A. cinereus kecilensis. M. K. A. Rosli, S. M. F. Syed-Shabthar, P. Abdul-Patah, Z. Abdul-Samad, S. N. Abdul, M. N. Burhanuddin, N. A. Zulkifli, M. N. Shukor, K. Budsabong, S. Changtragoon, T. Sekiguchi, H. Sasaki, and B. M. Md-Zain Copyright © 2014 M. K. A. Rosli et al. All rights reserved. Mink S38G Gene Polymorphism and Atrial Fibrillation in the Chinese Population: A Meta-Analysis of 1871 Participants Sun, 16 Feb 2014 11:32:01 +0000 Mink gene S38G polymorphism in the β-subunit of slow activating component of the delayed rectifier potassium channel current potassium channel has been associated with increased atrial fibrillation (AF) risk. However, the individual studies results were still controversial. To investigate the association of Mink S38G gene polymorphisms with AF, a meta-analysis including 1871 subjects from six individual studies was conducted. Mink S38G gene polymorphism was significantly related to AF under allelic (OR: 1.380, 95% CI: , ), recessive (OR: 1.193, 95% CI: , ), dominant (OR: 1.057, 95% CI: , ), additive (OR: 1.105, 95% CI: , ), homozygous (OR: 1.128, 95% CI: , ), and heterozygous genetic models (OR: 1.078, 95% CI: , ). A significant association between Mink S38G gene polymorphism and AF risk was found. G allele carriers may predispose to AF. Yan-yan Li, Lian-sheng Wang, and Xin-zheng Lu Copyright © 2014 Yan-yan Li et al. All rights reserved. Selection Index in the Study of Adaptability and Stability in Maize Thu, 13 Feb 2014 10:04:51 +0000 This paper proposes an alternative method for evaluating the stability and adaptability of maize hybrids using a genotype-ideotype distance index (GIDI) for selection. Data from seven variables were used, obtained through evaluation of 25 maize hybrids at six sites in southern Brazil. The GIDI was estimated by means of the generalized Mahalanobis distance for each plot of the test. We then proceeded to GGE biplot analysis in order to compare the predictive accuracy of the GGE models and the grouping of environments and to select the best five hybrids. The G × E interaction was significant for both variables assessed. The GGE model with two principal components obtained a predictive accuracy (PRECORR) of 0.8913 for the GIDI and 0.8709 for yield (t ha−1). Two groups of environments were obtained upon analyzing the GIDI, whereas all the environments remained in the same group upon analyzing yield. Coincidence occurred in only two hybrids considering evaluation of the two features. The GIDI assessment provided for selection of hybrids that combine adaptability and stability in most of the variables assessed, making its use more highly recommended than analyzing each variable separately. Not all the higher-yielding hybrids were the best in the other variables assessed. Rogério Lunezzo de Oliveira, Renzo Garcia Von Pinho, Daniel Furtado Ferreira, Luiz Paulo Miranda Pires, and Wagner Mateus Costa Melo Copyright © 2014 Rogério Lunezzo de Oliveira et al. All rights reserved. Karyotype Patterns of Hypsolebias antenori (Cyprinodontiformes: Rivulidae): An Endangered Killifish of the Semiarid Region of Brazil Tue, 11 Feb 2014 06:58:43 +0000 Annual fish which belong to the order Cyprinodontiformes constitute an excellent model for evolutionary studies. their short life cycle, distribution in ecologically dynamic environments, and low agility make them favorable for genetic analyses. The species Hypsolebias antenori (Rivulidae), encountered in seasonal pools located in the semiarid region of Northeastern Brazil, has been the object of surveys with a view to study its ecological and behavioral aspects. This study reports on the karyotype patterns of this species, which represents the first contribution to the cytogenetics of this genus. The karyotype of this species is composed of 2n = 48 chromosomes (6m + 4sm + 36st; NF = 96); the heterochromatic regions are located in centromeric or pericentromeric position and are more pronounced in the nucleolar organizer regions. Two sites Ag-NORs/CMA+/DAPI were identified in the short arms of pairs 2 (metacentric) and 21 (subtelocentric). Unlike the other species of this family which show an evolution modulated by events of centric fusions, H. antenori shows the maintenance of a basal diploid number and the large number of bibrachial elements indicates karyotypic diversification derived by pericentric inversions. Cytogenetic analyzes in this species will provide new taxonomic markers capable of being utilized in conservation issues and systematics. Wallace Silva do Nascimento, Juliana Galvão Bezerra, Paulo Augusto Lima-Filho, Maria Emília Yamamoto, Sathyabama Chellappa, and Wagner Franco Molina Copyright © 2014 Wallace Silva do Nascimento et al. All rights reserved. Competing Endogenous RNA: The Key to Posttranscriptional Regulation Sun, 02 Feb 2014 13:30:50 +0000 Competing endogenous RNA, ceRNA, vie with messenger RNAs (mRNAs) for microRNAs (miRNAs) with shared miRNAs responses elements (MREs) and act as modulator of miRNA by influencing the available level of miRNA. It has recently been discovered that, apart from protein-coding ceRNAs, pseudogenes, long noncoding RNAs (lncRNAs), and circular RNAs act as miRNA “sponges” by sharing common MRE, inhibiting normal miRNA targeting activity on mRNA. These MRE sharing elements form the posttranscriptional ceRNA network to regulate mRNA expression. ceRNAs are widely implicated in many biological processes. Recent studies have identified ceRNAs associated with a number of diseases including cancer. This brief review focuses on the molecular mechanism of ceRNA as part of the complex post-transcriptional regulatory circuit in cell and the impact of ceRNAs in development and disease. Rituparno Sen, Suman Ghosal, Shaoli Das, Subrata Balti, and Jayprokas Chakrabarti Copyright © 2014 Rituparno Sen et al. All rights reserved. Impact of Genes and Proportional Contribution of Parental Genotypes to Inheritance of Root Yield and Sugar Content in Diploid Hybrids of Sugar Beet Tue, 28 Jan 2014 09:10:47 +0000 This paper analyzes the impact of genes and proportional contribution of parental genotypes on the inheritance of root yield and sugar content in diploid hybrids of sugar beet. The survey included two diploid male-sterile monogerm lines and three single (SC) male-sterile hybrids as maternal components, while three multigerm diploids were used as pollinators. The partitioning of genotypic variance into additive and dominant components was performed by half sibling (HS) and full sibling (FS) covariance. The proportional contribution of individual components of crossbreeding (lines, testers, and interactions) was exhibited in the expression of certain characteristics of F1 generation. Genotypic variance components showed a significant effect of nonadditive gene action (dominance) in the inheritance of root yield and sugar content, while the additive effect of genes was less significant. Maternal components had a greater proportional contribution to root yield, while lines, pollinators, and their interactions had an equal contribution to sugar content. Ivica Stancic, Jelica Zivic, Sasa Petrovic, and Desimir Knezevic Copyright © 2014 Ivica Stancic et al. All rights reserved. RNAi-Mediated Knockdown of IKK1 in Transgenic Mice Using a Transgenic Construct Containing the Human H1 Promoter Sun, 12 Jan 2014 00:00:00 +0000 Inhibition of gene expression through siRNAs is a tool increasingly used for the study of gene function in model systems, including transgenic mice. To achieve perdurable effects, the stable expression of siRNAs by an integrated transgenic construct is necessary. For transgenic siRNA expression, promoters transcribed by either RNApol II or III (such as U6 or H1 promoters) can be used. Relatively large amounts of small RNAs synthesis are achieved when using RNApol III promoters, which can be advantageous in knockdown experiments. To study the feasibility of H1 promoter-driven RNAi-expressing constructs for protein knockdown in transgenic mice, we chose IKK1 as the target gene. Our results indicate that constructs containing the H1 promoter are sensitive to the presence of prokaryotic sequences and to transgene position effects, similar to RNApol II promoters-driven constructs. We observed variable expression levels of transgenic siRNA among different tissues and animals and a reduction of up to 80% in IKK1 expression. Furthermore, IKK1 knockdown led to hair follicle alterations. In summary, we show that constructs directed by the H1 promoter can be used for knockdown of genes of interest in different organs and for the generation of animal models complementary to knockout and overexpression models. Rodolfo Moreno-Maldonado, Rodolfo Murillas, Manuel Navarro, Angustias Page, Cristian Suarez-Cabrera, Josefa P. Alameda, Ana Bravo, M. Llanos Casanova, and Angel Ramirez Copyright © 2014 Rodolfo Moreno-Maldonado et al. All rights reserved. Identification of Leaf Rust Resistance Genes in Selected Egyptian Wheat Cultivars by Molecular Markers Mon, 06 Jan 2014 13:43:04 +0000 Leaf rust, caused by Puccinia triticina Eriks., is a common and widespread disease of wheat (Triticum aestivum L.) in Egypt. Host resistance is the most economical, effective, and ecologically sustainable method of controlling the disease. Molecular markers help to determine leaf rust resistance genes (Lr genes). The objective of this study was to identify Lr genes in fifteen wheat cultivars from Egypt. Ten genes, Lr13, Lr19, Lr24, Lr26, Lr34, Lr35 Lr36, Lr37, Lr39, and Lr46, were detected in fifteen wheat cultivars using various molecular markers. The most frequently occurring genes in fifteen Egyptian wheat cultivars were Lr13, Lr24, Lr34, and Lr36 identified in all the cultivars used, followed by Lr26 and Lr35 (93%), Lr39 (66%), Lr37 (53%), and Lr46 (26.6%) of the cultivars, and finally Lr19 was present in 33.3% of cultivars. It is concluded that there was a good variation in Lr genes carried by wheat cultivars commercially grown in Egypt. Therefore, strategies for deploying resistance genes to prolong effective disease resistance are suggested to control wheat leaf rust disease. I. A. Imbaby, M. A. Mahmoud, M. E. M. Hassan, and A. R. M. Abd-El-Aziz Copyright © 2014 I. A. Imbaby et al. All rights reserved. MicroRNA in Cervical Cancer: OncomiRs and Tumor Suppressor miRs in Diagnosis and Treatment Thu, 02 Jan 2014 14:05:40 +0000 Cervical cancer is a female-specific disease with a high incidence and mortality. MicroRNAs (miRNAs) are implicated in posttranscriptional regulation of gene expression and in the pathogenic mechanisms of cancer, suggesting their importance in diagnosis and treatment. miRNAs may have roles in the pathogenesis of cervical cancer based on the increases or decreases in several specific miRNAs found in patients with this disease. The miRNAs implicated in cervical cancer are miR-21, miR-126, and miR-143, and clinical application of these miRNAs for diagnosis and treatment is under investigation. Methods for diagnosis of cervical cancer include analysis of changes in the levels of specific miRNAs in serum and determination of aberrant hypermethylation of miRNAs. Supplementation of miR-143 or inhibition of miR-21 activity in vivo may be therapeutic strategy for cervical cancer. Previous approaches to development of siRNA as a drug have provided information for establishment of therapy based on these approaches, and an anti-miR-21 inhibitor has been developed. miRNAs also have effects on drug resistance and may be useful in combination therapy with other drugs. Kouji Banno, Miho Iida, Megumi Yanokura, Iori Kisu, Takashi Iwata, Eiichiro Tominaga, Kyoko Tanaka, and Daisuke Aoki Copyright © 2014 Kouji Banno et al. All rights reserved. Genetic Variants of Neurotransmitter-Related Genes and miRNAs in Egyptian Autistic Patients Mon, 23 Dec 2013 09:11:33 +0000 Autism is a neurodevelopmental disorder with indisputable evidence for a genetic component. This work studied the association of autism with genetic variations in neurotransmitter-related genes, including MAOA uVNTR, MAOB rs1799836, and DRD2 TaqI A in 53 autistic patients and 30 healthy individuals. The study also analyzed sequence variations of miR-431 and miR-21. MAOA uVNTR was genotyped by PCR, MAOB and DRD2 polymorphisms were analyzed by PCR-based RFLP, and miR-431 and miR-21 were sequenced. Low expressing allele of MAOA uVNTR was frequently higher in female patients compared to that in controls (OR = 2.25). MAOB G allele frequency was more significantly increased in autistic patients than in controls ( for both males and females). DRD2 A1+ genotype increased autism risk (OR = 5.1). Severity of autism tends to be slightly affected by MAOA/B genotype. Plasma MAOB activity was significantly reduced in G than in A allele carrying males. There was no significant difference in patients and maternal plasma MAOA/B activity compared to controls. Neither mutations nor SNPs in miR-431 and miR-21 were found among studied patients. This study threw light on some neurotransmitter-related genes suggesting their potential role in Autism pathogenesis that warrants further studies and much consideration. Ahmed M. Salem, Samira Ismail, Waheba A. Zarouk, Olwya Abdul Baky, Ahmed A. Sayed, Sawsan Abd El-Hamid, and Sohair Salem Copyright © 2013 Ahmed M. Salem et al. All rights reserved. Morphological Characterization of Cherry Rootstock Candidates Selected from Central and East Black Sea Regions in Turkey Wed, 18 Dec 2013 12:48:11 +0000 The use of rootstocks particularly for sweet cherry cultivars is of great importance for successful and sustainable production. Choosing the right cherry rootstocks is just as important as choosing the right cultivar. In this study, 110 sweet cherry, 30 sour cherry, and 41 mahaleb types displaying rootstock potential for sweet cherry cultivars were selected from Central and East Black Sea Regions in Turkey. The morphologic characteristics of the studied genotypes were compared with the standard clonal rootstocks PHL-A, MaxMa 14, Montmorency, Weiroot 158, Gisela 5, Gisela 6, and SL 64. A total of 42 morphological UPOV characteristics were evaluated in the selected genotypes and clonal rootstocks. The obtained data were analyzed by using principal component analysis and it revealed that eigenvalues of the first 3 components were able to represent 36.43% of total variance. The most significant positive correlations of the plant vigor were determined with leaf blade length and petiole thickness. According to the diversity analysis of coefficients, the 05 C 002 and 08 C 039 genotypes were identified as being similar (6.66), while the 05 C 002 and 55 S 012 genotypes were determined as the most distant genotypes (325.84) in terms of morphology. Aysen Koc, Zumrut Celik, Mustafa Akbulut, Sukriye Bilgener, Sezai Ercisli, Mehmet Gunes, Resul Gercekcioglu, and Ahmet Esitken Copyright © 2013 Aysen Koc et al. All rights reserved. Characterisation of Asian Snakehead Murrel Channa striata (Channidae) in Malaysia: An Insight into Molecular Data and Morphological Approach Thu, 12 Dec 2013 10:58:13 +0000 Conservation is imperative for the Asian snakeheads Channa striata, as the species has been overfished due to its high market demand. Using maternal markers (mitochondrial cytochrome c oxidase subunit 1 gene (COI)), we discovered that evolutionary forces that drove population divergence did not show any match between the genetic and morphological divergence pattern. However, there is evidence of incomplete divergence patterns between the Borneo population and the populations from Peninsular Malaysia. This supports the claim of historical coalescence of C. striata during Pleistocene glaciations. Ecological heterogeneity caused high phenotypic variance and was not correlated with genetic variance among the populations. Spatial conservation assessments are required to manage different stock units. Results on DNA barcoding show no evidence of cryptic species in C. striata in Malaysia. The newly obtained sequences add to the database of freshwater fish DNA barcodes and in future will provide information relevant to identification of species. Li Min Song, Kaviarasu Munian, Zulkafli Abd Rashid, and Subha Bhassu Copyright © 2013 Li Min Song et al. All rights reserved. Association of FAS and FAS Ligand Genes Polymorphism and Risk of Systemic Lupus Erythematosus Thu, 14 Nov 2013 18:54:17 +0000 FAS/FASL pathway plays a critical role in maintaining peripheral immune tolerance; therefore, the apoptosis genes, Fas and Fas ligand (FasL), could be suitable candidate genes in human SLE susceptibility. Materials and Methods. In this case-control study, 106 SLE patients and 149 sex, age, and ethnicity matched healthy controls were genotyped for the Fas A-670G and FasLC-844T polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Results. The frequency of -670AA genotype was significantly higher in SLE patients than control group and the risk of SLE was 2.1-fold greater in subjects with AA genotype (). The frequency of -670A allele was significantly higher in SLE patients than in controls too (58% versus 49%, ). The -844CC genotype frequency was significantly higher in SLE patients than in healthy controls and the risk of SLE was 2.8-fold greater in these subjects (). The C allele frequency was significantly higher in patients than in controls (69% versus 49%, ). Increased SLE risk was observed in individuals with combined effect of Fas-670AA and FasL-844CC genotypes (). Conclusion. Fas-670AA and FasL-844CC genotypes were associated with SLE risk, and combined effect of -670AA and -844CC genotypes might increase SLE susceptibility. Bita Moudi, Saeedeh Salimi, Farzaneh Farajian Mashhadi, Mahnaz Sandoughi, and Zahra Zakeri Copyright © 2013 Bita Moudi et al. All rights reserved. The Efficacy of Molecular Markers Analysis with Integration of Sensory Methods in Detection of Aroma in Rice Wed, 09 Oct 2013 09:00:42 +0000 Allele Specific Amplification with four primers (External Antisense Primer, External Sense Primer, Internal Nonfragrant Sense Primer, and Internal Fragrant Antisense Primer) and sensory evaluation with leaves and grains were executed to identify aromatic rice genotypes and their F1 individuals derived from different crosses of 2 Malaysian varieties with 4 popular land races and 3 advance lines. Homozygous aromatic (fgr/fgr) F1 individuals demonstrated better aroma scores compared to both heterozygous nonaromatic (FGR/fgr) and homozygous nonaromatic (FGR/FGR) individuals, while, some F1 individuals expressed aroma in both leaf and grain aromatic tests without possessing the fgr allele. Genotypic analysis of F1 individuals for the fgr gene represented homozygous aromatic, heterozygous nonaromatic and homozygous nonaromatic genotypes in the ratio 20 : 19 : 3. Genotypic and phenotypic analysis revealed that aroma in F1 individuals was successfully inherited from the parents, but either molecular analysis or sensory evaluation alone could not determine aromatic condition completely. The integration of molecular analysis with sensory methods was observed as rapid and reliable for the screening of aromatic genotypes because molecular analysis could distinguish aromatic homozygous, nonaromatic homozygous and nonaromatic heterozygous individuals, whilst the sensory method facilitated the evaluation of aroma emitted from leaf and grain during flowering to maturity stages. H. Y. Yeap, G. Faruq, H. P. Zakaria, and J. A. Harikrishna Copyright © 2013 H. Y. Yeap et al. All rights reserved. Mutations in MC1R Gene Determine Black Coat Color Phenotype in Chinese Sheep Tue, 03 Sep 2013 15:22:32 +0000 The melanocortin receptor 1 (MC1R) plays a central role in regulation of animal coat color formation. In this study, we sequenced the complete coding region and parts of the 5′- and 3′-untranslated regions of the MC1R gene in Chinese sheep with completely white (Large-tailed Han sheep), black (Minxian Black-fur sheep), and brown coat colors (Kazakh Fat-Rumped sheep). The results showed five single nucleotide polymorphisms (SNPs): two non-synonymous mutations previously associated with coat color (c.218 T>A, p.73 Met>Lys. c.361 G>A, p.121 Asp>Asn) and three synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu. c.735 C>T, p.245 Ile>Ile). Meanwhile, all mutations were detected in Minxian Black-fur sheep. However, the two nonsynonymous mutation sites were not in all studied breeds (Large-tailed Han, Small-tailed Han, Gansu Alpine Merino, and China Merino breeds), all of which are in white coat. A single haplotype AATGT (haplotype3) was uniquely associated with black coat color in Minxian Black-fur breed (, chi-square test). The first and second A alleles in this haplotype 3 represent location at 218 and 361 positions, respectively. Our results suggest that the mutations of MC1R gene are associated with black coat color phenotype in Chinese sheep. Guang-Li Yang, Dong-Li Fu, Xia Lang, Yu-Tao Wang, Shu-Ru Cheng, Su-Li Fang, and Yu-Zhu Luo Copyright © 2013 Guang-Li Yang et al. All rights reserved. Effects of Ginseng and Echinacea on Cytokine mRNA Expression in Rats Tue, 22 May 2012 15:55:23 +0000 The aim of the study was to determine the effect of ginseng and echinacea on the mRNA expression of IL-10, TNF-α, and TGF-β1 in healthy rats. Six-week-old male Fischer 344 rats (𝑛=48) were used. The animals were divided into three equal groups, as follows: control (C); ginseng (G); echinacea (E). While the C group was fed a standard rat diet (Purina) ad libitum for a period of 40 days, the G and E groups animals received the same diet containing 0.5 g/kg of Panax ginseng root powder and 0.75 g/kg of Echinacea purpurea root powder, respectively. Blood samples were obtained from 8 rats in each group after 20 and 40 days of treatment, and the mRNA expression of IL-10, TNF-α, and TGF-β1 was determined. After 20 days of treatment, the expression of IL-10 mRNA in the G group was different from the C group (𝑃<0.05); however, after 40 days of treatment, there was no difference between the groups. There was no difference after 20 and 40 days of treatment between the groups with respect to the expression of TGF-β1 mRNA. After 20 days of treatment, the expression of TNF-α mRNA in the E group was higher (𝑃<0.05) than the C group. After 40 days of treatment, the expression of TNF-α mRNA was similar in all of the groups. Based on the current study, the increase in expression of IL-10 mRNA in the G group and the increase in expression of TNF-α mRNA in the E group support the use of these plants for purposes of modulating the immune system. However, a more detailed study regarding the effects of ginseng and echinacea on these cytokines and other cytokines is needed. Deniz Uluışık and Ercan Keskin Copyright © 2012 Deniz Uluışık and Ercan Keskin. All rights reserved. The “Bringing into Cultivation” Phase of the Plant Domestication Process and Its Contributions to In Situ Conservation of Genetic Resources in Benin Tue, 22 May 2012 15:34:12 +0000 All over the world, plant domestication is continually being carried out by local communities to support their needs for food, fibre, medicine, building materials, etc. Using participatory rapid appraisal approach, 150 households were surveyed in 5 villages selected in five ethnic groups of Benin, to investigate the local communities’ motivations for plant domestication and the contributions of this process to in situ conservation of genetic resources. The results indicated differences in plant domestication between agroecological zones and among ethnic groups. People in the humid zones give priority to herbs mainly for their leaves while those in dry area prefer trees mostly for their fruits. Local communities were motivated to undertake plant domestication for foods (80% of respondents), medicinal use (40% of respondents), income generation (20% of respondents) and cultural reasons (5% of respondents). 45% of the species recorded are still at early stage in domestication and only 2% are fully domesticated. Eleven factors related to the households surveyed and to the head of the household interviewed affect farmers’ decision making in domesticating plant species. There is gender influence on the domestication: Women are keen in domesticating herbs while men give priority to trees. R. Vodouhè and A. Dansi Copyright © 2012 R. Vodouhè and A. Dansi. All rights reserved. A Genetic Approach to Spanish Populations of the Threatened Austropotamobius italicus Located at Three Different Scenarios Thu, 03 May 2012 09:09:58 +0000 Spanish freshwater ecosystems are suffering great modification and some macroinvertebrates like Austropotamobius italicus, the white-clawed crayfish, are threatened. This species was once widely distributed in Spain, but its populations have shown a very strong decline over the last thirty years, due to different factors. Three Spanish populations of this crayfish—from different scenarios—were analysed with nuclear (microsatellites) and mitochondrial markers (COI and 16S rDNA). Data analyses reveal the existence of four haplotypes at mitochondrial level and polymorphism for four microsatellite loci. Despite this genetic variability, bottlenecks were detected in the two natural Spanish populations tested. In addition, the distribution of the mitochondrial haplotypes and SSR alleles show a similar geographic pattern and the genetic differentiation between these samples is mainly due to genetic drift. Given the current risk status of the species across its range, this diversity offers some hope for the species from a management point of view. Beatriz Matallanas, Carmen Callejas, and M. Dolores Ochando Copyright © 2012 Beatriz Matallanas et al. All rights reserved. Mutation at the Human D1S80 Minisatellite Locus Thu, 03 May 2012 08:55:19 +0000 Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7) mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB) guidelines, we found a male mutation rate of 1.04×10-4 and a female mutation rate of 5.18×10-5 with an overall mutation rate of approximately 7.77×10-5. Also, in this study, we found that the identified mutations are in close proximity to the center of the repeat array rather than at the ends of the repeat array. Several studies have examined the mutational mechanisms of the minisatellites according to infinite allele model (IAM) and the one-step stepwise mutation model (SMM). In this study, we found that this locus fits into the one-step mutation model (SMM) mechanism in six out of seven instances similar to STR loci. Kuppareddi Balamurugan, Martin L. Tracey, Uwe Heine, George C. Maha, and George T. Duncan Copyright © 2012 Kuppareddi Balamurugan et al. All rights reserved. Influence of Codon Bias on Heterologous Production of Human Papillomavirus Type 16 Major Structural Protein L1 in Yeast Wed, 02 May 2012 19:16:16 +0000 Heterologous gene expression is dependent on multistep processes involving regulation at the level of transcription, mRNA turnover, protein translation, and posttranslational modifications. Codon bias has a significant influence on protein yields. However, sometimes it is not clear which parameter causes observed differences in heterologous gene expression as codon adaptation typically optimizes many sequence properties at once. In the current study, we evaluated the influence of codon bias on heterologous production of human papillomavirus type 16 (HPV-16) major structural protein L1 in yeast by expressing five variants of codon-modified open reading frames (OFRs) encoding HPV-16 L1 protein. Our results showed that despite the high toleration of various codons used throughout the length of the sequence of heterologously expressed genes in transformed yeast, there was a significant positive correlation between the gene's expression level and the degree of its codon bias towards the favorable codon usage. The HPV-16 L1 protein expression in yeast can be optimized by adjusting codon composition towards the most preferred codon adaptation, and this effect most probably is dependent on the improved translational elongation. Milda Norkiene and Alma Gedvilaite Copyright © 2012 Milda Norkiene and Alma Gedvilaite. All rights reserved. Biomarker Identification for Prostate Cancer and Lymph Node Metastasis from Microarray Data and Protein Interaction Network Using Gene Prioritization Method Wed, 02 May 2012 13:35:15 +0000 Finding a genetic disease-related gene is not a trivial task. Therefore, computational methods are needed to present clues to the biomedical community to explore genes that are more likely to be related to a specific disease as biomarker. We present biomarker identification problem using gene prioritization method called gene prioritization from microarray data based on shortest paths, extended with structural and biological properties and edge flux using voting scheme (GP-MIDAS-VXEF). The method is based on finding relevant interactions on protein interaction networks, then scoring the genes using shortest paths and topological analysis, integrating the results using a voting scheme and a biological boosting. We applied two experiments, one is prostate primary and normal samples and the other is prostate primary tumor with and without lymph nodes metastasis. We used 137 truly prostate cancer genes as benchmark. In the first experiment, GP-MIDAS-VXEF outperforms all the other state-of-the-art methods in the benchmark by retrieving the truest related genes from the candidate set in the top 50 scores found. We applied the same technique to infer the significant biomarkers in prostate cancer with lymph nodes metastasis which is not established well. Carlos Roberto Arias, Hsiang-Yuan Yeh, and Von-Wun Soo Copyright © 2012 Carlos Roberto Arias et al. All rights reserved. Random Amplified Polymorphic Markers as Indicator for Genetic Conservation Program in Iranian Pheasant (Phasianus colchicus) Wed, 02 May 2012 12:28:51 +0000 The objective of present study was identification of genetic similarity between wild Iran and captive Azerbaijan Pheasant using PCR-RAPD markers. For this purpose, in overall, 28 birds were taken for DNA extraction and subsequently 15 arbitrary primers were applied for PCR-RAPD technique. After electrophoresis, five primers exhibited sufficient variability which yielded overall 65 distinct bands, 59 polymorphic bands, for detalis, range of number of bands per primer was 10 to 14, and produced size varied between 200 to 1500 bp. Highest and lowest polymorphic primers were OPC5, OPC16 (100%) and OPC15 (81%), respectively. Result of genetic variation between two groups was accounted as nonsignificant (8.12%) of the overall variation. According to our expectation the wild Iranian birds showed higher genetic diversity value than the Azerbaijan captive birds. As general conclusion, two pheasant populations have almost same genetic origin and probably are subpopulations of one population. The data reported herein could open the opportunity to search for suitable conservation strategy to improve richness of Iran biodiversity and present study here was the first report that might have significant impact on the breeding and conservation program of Iranian pheasant gene pool. Analyses using more regions, more birds, and more DNA markers will be useful to confirm or to reject these findings. Ghorban Elyasi Zarringhabaie, Arash Javanmard, and Ommolbanin Pirahary Copyright © 2012 Ghorban Elyasi Zarringhabaie et al. All rights reserved. Wild Termitomyces Species Collected from Ondo and Ekiti States Are More Related to African Species as Revealed by ITS Region of rDNA Wed, 02 May 2012 11:42:32 +0000 Molecular identification of eighteen Termitomyces species collected from two states, Ondo and Ekiti in Nigeria was carried out using the internal transcribed spacer (ITS) region. The amplicons obtained from rDNA of Termitomyces species were compared with existing sequences in the NCBI GenBank. The results of the ITS sequence analysis discriminated between all the Termitomyces species (obtained from Ondo and Ekiti States) and Termitomyces sp. sequences obtained from NCBI GenBank. The degree of similarity of T1 to T18 to gene of Termitomyces sp. obtained from NCBI ranges between 82 and 99 percent. Termitomyces species from Garbon with ascension number AF321374 was the closest relative of T1 to T18 except T12 that has T. eurhizus and T. striatus as the closet relative. Phylogenetic tree generated with ITS sequences obtained from NCBI GenBank data revealed that T1 to T18 are more related to Termitomyces species indigenous to African countries such as Senegal, Congo, and Gabon. Victor Olusegun Oyetayo Copyright © 2012 Victor Olusegun Oyetayo. All rights reserved. New Insights in the Sugarcane Transcriptome Responding to Drought Stress as Revealed by Supersage Wed, 02 May 2012 10:59:59 +0000 In the scope of the present work, four SuperSAGE libraries have been generated, using bulked root tissues from four drought-tolerant accessions as compared with four bulked sensitive genotypes, aiming to generate a panel of differentially expressed stress-responsive genes. Both groups were submitted to 24 hours of water deficit stress. The SuperSAGE libraries produced 8,787,315 tags (26 bp) that, after exclusion of singlets, allowed the identification of 205,975 unitags. Most relevant BlastN matches comprised 567,420 tags, regarding 75,404 unitags with 164,860 different ESTs. To optimize the annotation efficiency, the Gene Ontology (GO) categorization was carried out for 186,191 ESTs (BlastN against Uniprot-SwissProt), permitting the categorization of 118,208 ESTs (63.5%). In an attempt to elect a group of the best tags to be validated by RTqPCR, the GO categorization of the tag-related ESTs allowed the in silico identification of 213 upregulated unitags responding basically to abiotic stresses, from which 145 presented no hits after BlastN analysis, probably concerning new genes still uncovered in previous studies. The present report analyzes the sugarcane transcriptome under drought stress, using a combination of high-throughput transcriptome profiling by SuperSAGE with the Solexa sequencing technology, allowing the identification of potential target genes during the stress response. Éderson Akio Kido, José Ribamar Costa Ferreira Neto, Roberta Lane de Oliveira Silva, Valesca Pandolfi, Ana Carolina Ribeiro Guimarães, Daniela Truffi Veiga, Sabrina Moutinho Chabregas, Sérgio Crovella, and Ana Maria Benko-Iseppon Copyright © 2012 Éderson Akio Kido et al. All rights reserved. Genetics and Epigenetics of Parkinson's Disease Tue, 01 May 2012 15:55:12 +0000 In 1997 a mutation in the a-synuclein (SNCA) gene was associated with familial autosomal dominant Parkinson’s disease (PD). Since then, several loci (PARK1-15) and genes have been linked to familial forms of the disease. There is now sufficient evidence that six of the so far identified genes at PARK loci (a-synuclein, leucine-rich repeat kinase 2, parkin, PTEN-induced putative kinase 1, DJ-1, and ATP13A2) cause inherited forms of typical PD or parkinsonian syndromes. Other genes at non-PARK loci (MAPT, SCA1, SCA2, spatacsin, POLG1) cause syndromes with parkinsonism as one of the symptoms. The majority of PD cases are however sporadic “idiopathic” forms, and the recent application of genome-wide screening revealed almost 20 genes that might contribute to disease risk. In addition, increasing evidence suggests that epigenetic mechanisms, such as DNA methylation, histone modifications, and small RNA-mediated mechanisms, could regulate the expression of PD-related genes. Fabio Coppedè Copyright © 2012 Fabio Coppedè. All rights reserved. Genetic Diversity of Upland Rice Germplasm in Malaysia Based on Quantitative Traits Mon, 30 Apr 2012 14:22:49 +0000 Genetic diversity is prerequisite for any crop improvement program as it helps in the development of superior recombinants. Fifty Malaysian upland rice accessions were evaluated for 12 growth traits, yield and yield components. All of the traits were significant and highly significant among the accessions. The higher magnitudes of genotypic and phenotypic coefficients of variation were recorded for flag leaf length-to-width ratio, spikelet fertility, and days to flowering. High heritability along with high genetic advance was registered for yield of plant, days to flowering, and flag leaf length-to-width ratio suggesting preponderance of additive gene action in the gene expression of these characters. Plant height showed highly significant positive correlation with most of the traits. According to UPGMA cluster analysis all accessions were clustered into six groups. Twelve morphological traits provided around 77% of total variation among the accessions. M. Sohrabi, M. Y. Rafii, M. M. Hanafi, A. Siti Nor Akmar, and M. A. Latif Copyright © 2012 M. Sohrabi et al. All rights reserved. Allelic Variation at the Rht8 Locus in a 19th Century Wheat Collection Mon, 30 Apr 2012 11:38:48 +0000 Wheat breeding during the 20th century has put large efforts into reducing straw length and increasing harvest index. In the 1920s an allele of Rht8 with dwarfing effects, found in the Japanese cultivar “Akakomugi,” was bred into European cultivars and subsequently spread over the world. Rht8 has not been cloned, but the microsatellite marker WMS261 has been shown to be closely linked to it and is commonly used for genotyping Rht8. The “Akakomugi” allele is strongly associated with WMS261-192bp. Numerous screens of wheat cultivars with different geographical origin have been performed to study the spread and influence of the WMS261-192bp during 20th century plant breeding. However, the allelic diversity of WMS261 in wheat cultivars before modern plant breeding and introduction of the Japanese dwarfing genes is largely unknown. Here, we report a study of WMS261 allelic diversity in a historical wheat collection from 1865 representing worldwide major wheats at the time. The majority carried the previously reported 164 bp or 174 bp allele, but with little geographical correlation. In a few lines, a rare 182 bp fragment was found. Although straw length was recognized as an important character already in the 19th century, Rht8 probably played a minor role for height variation. The use of WMS261 and other functional markers for analyses of historical specimens and characterization of historic crop traits is discussed. Linnéa Asplund, Matti W. Leino, and Jenny Hagenblad Copyright © 2012 Linnéa Asplund et al. All rights reserved. Assessment of Tools for Marker-Assisted Selection in a Marine Commercial Species: Significant Association between MSTN-1 Gene Polymorphism and Growth Traits Mon, 30 Apr 2012 11:29:25 +0000 Growth is a priority trait from the point of view of genetic improvement. Molecular markers linked to quantitative trait loci (QTL) have been regarded as useful for marker-assisted selection in complex traits as growth. Polymorphisms have been studied in five candidate genes influencing growth in gilthead seabream (Sparus aurata): the growth hormone (GH), insulin-like growth factor-1 (IGF-1), myostatin (MSTN-1), prolactin (PRL), and somatolactin (SL) genes. Specimens evaluated were from a commercial broodstock comprising 131 breeders (from which 36 males and 44 females contributed to the progeny). In all samples eleven gene fragments, covering more than 13,000 bp, generated by PCR-RFLP, were analyzed; tests were made for significant associations between these markers and growth traits. ANOVA results showed a significant association between MSTN-1 gene polymorphism and growth traits. Pairwise tests revealed several RFLPs in the MSTN-1 gene with significant heterogeneity of genotypes among size groups. PRL and MSTN-1 genes presented linkage disequilibrium. The MSTN-1 gene was mapped in the centromeric region of a medium-size acrocentric chromosome pair. Irma Sánchez-Ramos, Ismael Cross, Jaroslav Mácha, Gonzalo Martínez-Rodríguez, Vladimir Krylov, and Laureana Rebordinos Copyright © 2012 Irma Sánchez-Ramos et al. All rights reserved. PTEN Gene: A Model for Genetic Diseases in Dermatology Mon, 30 Apr 2012 08:25:19 +0000 PTEN gene is considered one of the most mutated tumor suppressor genes in human cancer, and it’s likely to become the first one in the near future. Since 1997, its involvement in tumor suppression has smoothly increased, up to the current importance. Germline mutations of PTEN cause the PTEN hamartoma tumor syndrome (PHTS), which include the past-called Cowden, Bannayan-Riley-Ruvalcaba, Proteus, Proteus-like, and Lhermitte-Duclos syndromes. Somatic mutations of PTEN have been observed in glioblastoma, prostate cancer, and brest cancer cell lines, quoting only the first tissues where the involvement has been proven. The negative regulation of cell interactions with the extracellular matrix could be the way PTEN phosphatase acts as a tumor suppressor. PTEN gene plays an essential role in human development. A recent model sees PTEN function as a stepwise gradation, which can be impaired not only by heterozygous mutations and homozygous losses, but also by other molecular mechanisms, such as transcriptional regression, epigenetic silencing, regulation by microRNAs, posttranslational modification, and aberrant localization. The involvement of PTEN function in melanoma and multistage skin carcinogenesis, with its implication in cancer treatment, and the role of front office in diagnosing PHTS are the main reasons why the dermatologist should know about PTEN. Corrado Romano and Carmelo Schepis Copyright © 2012 Corrado Romano and Carmelo Schepis. All rights reserved. A Study of Epstein-Barr Virus BRLF1 Activity in a Drosophila Model System Thu, 26 Apr 2012 15:39:40 +0000 Epstein-Barr virus, a member of the herpesvirus family, infects a large majority of the human population and is associated with several diseases, including cancer. We have created Drosophila model systems to study the interactions between host cellular proteins and the Epstein-Barr virus (EBV) immediate-early genes BRLF1 and BZLF1. BRLF1 and BZLF1 function as transcription factors for viral transcription and are also potent modifiers of host cell activity. Here we have used our model systems to identify host cell genes whose proteins modulate BRLF1 and BZLF1 functions. Via our GMR-R model system, we have found that BRLF1 expression results in overproliferation of fly tissue, unlike BZLF1, and does so through the interaction with known tumor suppressor genes. Through an additional genetic screen, we have identified several Drosophila genes, with human homologs, that may offer further insights into the pathways that BRLF1 interacts with in order to promote EBV replication. Amy Adamson and Dennis LaJeunesse Copyright © 2012 Amy Adamson and Dennis LaJeunesse. All rights reserved. The c.1460C>T Polymorphism of MAO-A Is Associated with the Risk of Depression in Postmenopausal Women Tue, 24 Apr 2012 14:50:50 +0000 Objective. The aim of the study was an evaluation of possible relationships between polymorphisms of serotoninergic system genes and the risk of depression in postmenopausal women. Methods. We studied 332 women admitted to our department because of climacteric symptoms. The study group included 113 women with a diagnosis of depressive disorder according to the Hamilton rating scale for depression; the controls consisted of 219 women without depression. Serum 17β-estradiol concentrations were evaluated using radioimmunoassay, while polymorphisms in serotoninergic system genes: serotonin receptors 2A (HTR2A), 1B (HTR1B), and 2C (HTR2C); tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), and monoamine oxidase A (MAO-A) were evaluated using polymerase chain reaction-restriction. Results. We found that the 1460T allele of MAO-A c.1460C>T (SNP 1137070) appeared with a significantly higher frequency in depressed female patients than in the control group (𝑃=0.011) and the combined c.1460CT + TT genotypes were associated with a higher risk of depression (𝑃=0.0198). Patients with the 1460TT genotype had a significantly higher 17β-estradiol concentration than patients with the 1460CT genotype (𝑃=0.0065) and 1460CC genotype (𝑃=0.0018). Conclusions. We concluded that depression in postmenopausal women is closely related to the genetic contribution of MAO-A. R. Słopień, A. Słopień, A. Różycka, A. Warenik-Szymankiewicz, M. Lianeri, and P. P. Jagodziński Copyright © 2012 R. Słopień et al. All rights reserved. Genetic Dissection of Sympatric Populations of Brown Planthopper, Nilaparvata lugens (Stål), Using DALP-PCR Molecular Markers Thu, 19 Apr 2012 15:57:26 +0000 Direct amplified length polymorphism (DALP) combines the advantages of a high-resolution fingerprint method and also characterizing the genetic polymorphisms. This molecular method was also found to be useful in brown planthopper, Nilaparvata lugens species complex for the analysis of genetic polymorphisms. A total of 11 populations of Nilaparvata spp. were collected from 6 locations from Malaysia. Two sympatric populations of brown planthopper, N. lugens, one from rice and the other from a weed grass (Leersia hexandra), were collected from each of five locations. N. bakeri was used as an out group. Three oligonucleotide primer pairs, DALP231/DALPR′5, DALP234/DALPR′5, and DALP235/DALPR′5 were applied in this study. The unweighted pair group method with arithmetic mean (UPGMA) dendrogram based on genetic distances for the 11 populations of Nilaparvata spp. revealed that populations belonging to the same species and the same host type clustered together irrespective of their geographical localities of capture. The populations of N. lugens formed into two distinct clusters, one was insects with high esterase activities usually captured from rice and the other was with low esterase activities usually captured from L. hexandra. N. bakeri, an out group, was the most isolated group. Analyses of principal components, molecular variance, and robustness also supported greatly to the findings of cluster analysis. M. A. Latif, M. Y. Rafii, M. S. Mazid, M. E. Ali, F. Ahmed, M. Y. Omar, and S. G. Tan Copyright © 2012 M. A. Latif et al. All rights reserved. Flavonoid-Deficient Mutants in Grass Pea (Lathyrus sativus L.): Genetic Control, Linkage Relationships, and Mapping with Aconitase and S-Nitrosoglutathione Reductase Isozyme Loci Thu, 19 Apr 2012 14:57:27 +0000 Two flavonoid-deficient mutants, designated as fldL-1 and fldL-2, were isolated in EMS-mutagenized (0.15%, 10 h) M2 progeny of grass pea (Lathyrus sativus L.). Both the mutants contained total leaf flavonoid content only 20% of their mother varieties. Genetic analysis revealed monogenic recessive inheritance of the trait, controlled by two different nonallelic loci. The two mutants differed significantly in banding patterns of leaf aconitase (ACO) and S-nitrosoglutathione reductase (GSNOR) isozymes, possessing unique bands in Aco 1, Aco 2, and Gsnor 2 loci. Isozyme loci inherited monogenically showing codominant expression in F2 (1 : 2 : 1) and backcross (1 : 1) segregations. Linkage studies and primary trisomic analysis mapped Aco 1 and fld 1 loci on extra chromosome of trisomic-I and Aco 2, fld 2, and Gsnor 2 on extra chromosome of trisomic-IV in linked associations. Dibyendu Talukdar Copyright © 2012 Dibyendu Talukdar. All rights reserved. Evaluation of the Utility of the Random Amplified Polymorphic DNA Method and of the Semi-Specific PCR to Assess the Genetic Diversification of the Gerbera jamesonii Bolus Line Thu, 19 Apr 2012 12:08:17 +0000 An attempt was made to evaluate the utility of a method which employs semi-specific PCR using partially specific primers for the coding sequence (ET) at the exon-intron contact and of the RAPD method to identify eight Polish cultivars of gerbera. It was demonstrated that the PCR method which employs semi-specific primers is as simple and economical as the RAPD method, simultaneously the images of the multiplied by means of the semi-specific PCR method DNA fragments are more complex and polymorphic than those obtained through the RAPD method. The studies of the genetic diversification of Gerbera cultivars employing the aforementioned methods made it possible to conduct a concentration analysis and evaluation of the genetic distance between the lines, manifesting at the same time the superiority of the semi-random PCR method. Moreover, it transpired that the use of mixtures of RAPD primers not always leads to an increase of the number of generated polymorphic bands. Zbigniew Rusinowski and Olga Domeradzka Copyright © 2012 Zbigniew Rusinowski and Olga Domeradzka. All rights reserved. Distribution of BoLA-DRB3 Allelic Frequencies and Identification of Two New Alleles in Iranian Buffalo Breed Tue, 14 Feb 2012 14:44:42 +0000 The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 *48, *20, *21, and obe) in Iranian buffalo. The DRB3.2 *48 allele frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 *20 and DRB3.2 *21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found. J. Mosafer, M. Heydarpour, E. Manshad, G. Russell, and G. E. Sulimova Copyright © 2012 J. Mosafer et al. All rights reserved. Population Genetic Analysis of Lobelia rhynchopetalum Hemsl. (Campanulaceae) Using DNA Sequences from ITS and Eight Chloroplast DNA Regions Wed, 04 Jan 2012 10:55:29 +0000 DNA sequence data from the internal transcribed spacer of nuclear ribosomal DNA and eight chloroplast DNA regions were used to investigate haplotypic variation and population genetic structure of the Afroalpine giant lobelia, Lobelia rhynchopetalum. The study was based on eight populations sampled from two mountain systems in Ethiopia. A total of 20 variable sites were obtained, which resulted in 13 unique haplotypes and an overall nucleotide diversity (ND) of 0.281 ± 0.15 and gene diversity (GD) of 0.85 ± 0.04. Analysis of molecular variance (AMOVA) revealed a highly significant variation (𝑃<0.001) among populations (𝐹ST), and phylogenetic analysis revealed that populations from the two mountain systems formed their own distinct clade with >90% bootstrap support. Each population should be regarded as a significant unit for conservation of this species. The primers designed for this study can be applied to any Lobelia and other closely related species for population genetics and phylogenetic studies. Mulatu Geleta and Tomas Bryngelsson Copyright © 2012 Mulatu Geleta and Tomas Bryngelsson. All rights reserved. Mouse Models of Aneuploidy Tue, 03 Jan 2012 15:49:46 +0000 Abnormalities of chromosome copy number are called aneuploidies and make up a large health load on the human population. Many aneuploidies are lethal because the resulting abnormal gene dosage is highly deleterious. Nevertheless, some whole chromosome aneuploidies can lead to live births. Alterations in the copy number of sections of chromosomes, which are also known as segmental aneuploidies, are also associated with deleterious effects. Here we examine how aneuploidy of whole chromosomes and segmental aneuploidy of chromosomal regions are modeled in the mouse. These models provide a whole animal system in which we aim to investigate the complex phenotype-genotype interactions that arise from alteration in the copy number of genes. Although our understanding of this subject is still in its infancy, already research in mouse models is highlighting possible therapies that might help alleviate the cognitive effects associated with changes in gene number. Thus, creating and studying mouse models of aneuploidy and copy number variation is important for understanding what it is to be human, in both the normal and genomically altered states. Olivia Sheppard, Frances K. Wiseman, Aarti Ruparelia, Victor L. J. Tybulewicz, and Elizabeth M. C. Fisher Copyright © 2012 Olivia Sheppard et al. All rights reserved. An Overview of DNA Repair in Amyotrophic Lateral Sclerosis Mon, 17 Oct 2011 00:00:00 +0000 Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is an adult onset neurodegenerative disorder characterised by the degeneration of cortical and spinal cord motor neurons, resulting in progressive muscular weakness and death. Increasing evidence supports mitochondrial dysfunction and oxidative DNA damage in ALS motor neurons. Several DNA repair enzymes are activated following DNA damage to restore genome integrity, and impairments in DNA repair capabilities could contribute to motor neuron degeneration. After a brief description of the evidence of DNA damage in ALS, this paper focuses on the available data on DNA repair activity in ALS neuronal tissue and disease animal models. Moreover, biochemical and genetic data on DNA repair in ALS are discussed in light of similar findings in other neurodegenerative diseases. Fabio Coppedè Copyright © 2011 Fabio Coppedè. All rights reserved. MicroRNAs in Development Mon, 01 Jan 1900 00:00:00 +0000 Over 10 years ago, the lab of Victor Ambros cloned an unusual gene, lin-4, which encodes two small RNA transcripts[1]. In the past few years, hundreds more of these tiny transcripts, termed microRNAs (miRNAs), have been uncovered in over a dozen species. The functions of the first two miRNAs, lin-4 and let-7, were relatively easy to identify since they were found in forward genetic screens in Caenorhabditis elegans[1,2,3]. However, uncovering the functions of the growing list of miRNAs presents a challenge to developmental biologists. This review will describe our current understanding of how miRNAs regulate gene expression and will focus on the roles these noncoding RNAs play during the development of both invertebrate and vertebrate species. Danielle Maatouk and Brian D. Harfe Copyright © 2006 Danielle Maatouk and Brian Harfe. All rights reserved. B Cell Precursors in Senescent Mice Exhibit Decreased Mitotic Recruitment, Increased Apoptosis, and Altered Expression of Bcl-2 Family Members Mon, 01 Jan 1900 00:00:00 +0000 Richard L. Riley and Erin M. Sherwood Copyright © 2001 Richard L. Riley and Erin M. Sherwood. All rights reserved. Medial Position and Counterclockwise Rotation of the Parietal Scalp Hair-Whorl as a Possible Indicator for Non-Right-Handedness Mon, 01 Jan 1900 00:00:00 +0000 The objective of our study was to assess the association between position and swirling direction of the parietal whorl (PW) and handedness. In 519 patients of a pediatric practice, PWs were located and the swirling direction determined. Of those patients, handedness could be specified in 217. The right-sided PW (n = 347; 70.8%) and the clockwise (CW) swirling type (n = 411; 83.9%) of all participants were predominant in children with one PW. Non-right-handedness (NRH) was found in 40 (18.4%). Medial position of the whorl per se increases the chance for NRH, indifferent of the swirling direction. In patients with counterclockwise (CCW) swirling, the chance of NRH increased 3.5-fold for the right-sided, 5.4-fold for the left-sided, and 12.9-fold for the medial-positioned whorl. We conclude that NRH is associated with the position (medial!) and the swirling direction (CCW!) of the PW. Heinrich Schmidt, Martin Depner, and Michael Kabesch Copyright © 2008 Heinrich Schmidt et al. All rights reserved. The Relevance of Oncogene-Induced Apoptosis in Cancer Mon, 01 Jan 1900 00:00:00 +0000 Gerard Evan Copyright © 2001 Gerard Evan. All rights reserved. Current Challenges in Spina Bifida Care Mon, 01 Jan 1900 00:00:00 +0000 David B. Joseph Copyright © 2007 David B. Joseph. All rights reserved. DNA Evidence Uncompromised by Active Oxygen Mon, 01 Jan 1900 00:00:00 +0000 Currently, forensic sciences can make use of the potential of instrumental analysis techniques to obtain information from the smallest, even invisible, samples. However, as laboratory techniques improve, so too should the procedures applied in the search for and initial testing of clues in order to be equally effective. This requires continuous revision so that those procedures may resolve the problems that samples present. As far as bloodstains are concerned, there are methods available that are recognized as being both highly sensitive and effective. Nevertheless, the marketing of new cleaning products, those that contain active oxygen, has raised doubts about the ability of those procedures to detect blood. It has been shown that stains washed with these detergents (and still visible) invalidated both the presumptive test (reduced phenolphthalein, luminol, and Bluestar®) and that applied for determining human hemoglobin. These findings have caused considerable concern both within the forensic and scientific community, and among the general public, so obliging us to seek solutions. In this work, the effect of these new cleaning products on DNA analyses is studied. The results, encouraging ones, show that these detergents, despite invalidating all other tests, do not hinder the extraction, or the subsequent analysis, of DNA. Ana Castelló, Francesc Francés, and Fernando Verdú Copyright © 2010 Ana Castelló et al. All rights reserved. High-Resolution Northern Blot for a Reliable Analysis of MicroRNAs and Their Precursors Mon, 01 Jan 1900 00:00:00 +0000 This protocol describes how to perform northern blot analyses to detect microRNAs and their precursors with single-nucleotide resolution, which is crucial for analyzing individual length variants and for evaluating relative quantities of unique microRNAs in cells. Northern blot analysis consists of resolving RNAs by gel electrophoresis, followed by transferring and fixing to nylon membranes as well as detecting by hybridization with radioactive probes. Earlier efforts to improve this method focused mainly on altering the sensitivity of short RNA detection. We have enhanced the resolution of the northern blot technique by optimizing the electrophoresis step. We have also investigated other steps of the procedure with the goal of enhancing the resolution of RNAs; herein, we present several recommendations to do so. Our protocol is applicable to analyses of all kinds of endogenous and exogenous RNAs, falling within length ranges of 20–30 and 50–70 nt, corresponding to microRNA and pre-microRNA lengths, respectively. Edyta Koscianska, Julia Starega-Roslan, Katarzyna Czubala, and Wlodzimierz J. Krzyzosiak Copyright © 2011 Edyta Koscianska et al. All rights reserved. Familial Clustering of Unexplained Transient Respiratory Distress in 12 Newborns from Three Unrelated Families Suggests an Autosomal-Recessive Inheritance Mon, 01 Jan 1900 00:00:00 +0000 We report on 12 near-term babies from three families in which an unexplained transient respiratory distress was observed. No known risk factor was present in any family and no sequelae were recorded at follow-up. The most common causes of respiratory distress at birth are Neonatal Respiratory Distress Syndrome (NRD) and Transient Tachypnea of the Newborn (TTN), and their cumulative incidence is estimated to be about 2%. Genetic factors have been identified in NRD (surfactant genes) or suggested for TTN (genes affecting lung liquid clearance). Survivors from NRD may develop clinically relevant sequelae, while TTN does not cause any problem later in life. Our cases do not immediately fit NRD or TTN, while familial recurrence suggests the existence of a previously unreported subgroup on patients with respiratory distress for which autosomal-recessive inheritance is likely. Andrea Guala, Paola Carrera, Guido Pastore, Marco Somaschini, Gina Ancora, Giacomo Faldella, Paolo De Filippi, Federica Ferrero, Roberta Guarino, and Cesare Danesino Copyright © 2007 Andrea Guala et al. All rights reserved. Gene Transfer of CGRP Prevents Cerebral Vasoconstriction after Subarachnoid Hemorrhage Mon, 01 Jan 1900 00:00:00 +0000 Donald D. Heistad, Andrew F. Russo, Frank M. Faraci, and Christopher G. Sobey Copyright © 2001 Donald D. Heistad et al. All rights reserved. Multifunctional Receptor Stabilin-1 in Homeostasis and Disease Mon, 01 Jan 1900 00:00:00 +0000 The multifunctional scavenger receptor stabilin-1 (STAB1, FEEL-1, CLEVER-1, KIAA0246) is expressed on tissue macrophages and sinusoidal endothelial cells in healthy organisms, and its expression on both macrophages and different subtypes of endothelial cells is induced during chronic inflammation and tumor progression. Stabilin-1 is a type-1 transmembrane receptor that mediates endocytic and phagocytic clearance of “unwanted-self” components, intracellular sorting of the endogenously synthesized chitinase-like protein SI-CLP, and transcytosis of the growth hormone family member placental lactogen. The central sorting station for stabilin-1 trafficking seems to be the trans-Golgi network (TGN). Transport of stabilin-1 in the TGN requires interaction with GGA adaptors that bind to the classical DDSLL motif and a novel acidic cluster in its cytoplasmic tail. Degradation of stabilin-1 seems to depend on the interaction with sorting nexin 17. However, the mechanisms keeping stabilin-1 on the cell surface remain to be identified. This issue deserves specific attention due to the growing amount of data indicating that function of stabilin-1 in cell adhesion events is essential for inflammation and metastasis. Taking into consideration the complexity of stabilin-1—mediated processes, investigation of stabilin-1 functions in the animal models, as well as mathematic modeling of intracellular trafficking and extracellular contact, would enable prediction of stabilin-1 behavior in complex biological systems and would open perspectives for therapeutic targeting of stabilin-1 pathways in chronic inflammation and carcinogenesis. Julia Kzhyshkowska Copyright © 2010 Julia Kzhyshkowska. All rights reserved. Gene Expression is Selectively Affected along the Epididymis after Orchidectomy Mon, 01 Jan 1900 00:00:00 +0000 Nadine N. Ezer and Bernard Robaire Copyright © 2001 Nadine N. Ezer and Bernard Robaire. All rights reserved. Proteoglycans are Differentially Altered in Muscular Dystrophies Mon, 01 Jan 1900 00:00:00 +0000 Simona Zanotti and Marina Mora Copyright © 2006 Simona Zanotti and Marina Mora. All rights reserved. Cgrp Characterization And Classification Mon, 01 Jan 1900 00:00:00 +0000 The peptide CGRP is thought to be an agonist at a number of receptors including its own as well as those for adrenomedullin and amylin. CGRP is thought to act through its own receptors if it is antagonized by the truncated peptide CGRP8-37 although this assumes the specificity of the antagonist. Ian Marshall Copyright © 2001 Ian Marshall. All rights reserved. Design and Generation of MLPA Probe Sets for Combined Copy Number and Small-Mutation Analysis of Human Genes: EGFR as an Example Mon, 01 Jan 1900 00:00:00 +0000 Multiplex ligation-dependent probe amplification (MLPA) is a multiplex copy number analysis method that is routinely used to identify large mutations in many clinical and research labs. One of the most important drawbacks of the standard MLPA setup is a complicated, and therefore expensive, procedure of generating long MLPA probes. This drawback substantially limits the applicability of MLPA to those genomic regions for which ready-to-use commercial kits are available. Here we present a simple protocol for designing MLPA probe sets that are composed entirely of short oligonucleotide half-probes generated through chemical synthesis. As an example, we present the design and generation of an MLPA assay for parallel copy number and small-mutation analysis of the EGFR gene. Malgorzata Marcinkowska, Kwok-Kin Wong, David J. Kwiatkowski, and Piotr Kozlowski Copyright © 2010 Malgorzata Marcinkowska et al. All rights reserved. New Surprises from the Deep — The Family of Small Regulatory RNAs Increases Mon, 01 Jan 1900 00:00:00 +0000 Jürgen Wittmann and Hans-Martin Jäck Copyright © 2010 Jürgen Wittmann and Hans-Martin Jäck. All rights reserved. Ensuring the Stability of the Genome: DNA Damage Checkpoints Mon, 01 Jan 1900 00:00:00 +0000 The cellular response to DNA damage is vital for the cell�s ability to maintain genomic integrity. Checkpoint signalling pathways, which induce a cell cycle arrest in response to DNA damage, are an essential component of this process. This is reflected by the functional conservation of these pathways in all eukaryotes from yeast to mammalian cells. This review will examine the cellular response to DNA damage throughout the cell cycle. A key component of the DNA damage response is checkpoint signalling, which monitors the state of the genome prior to DNA replication (G1/S) and chromosome segregation (G2/M). Checkpoint signalling in model systems including mice, Xenopus laevis, Drosophila melanogaster, and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been useful in elucidating these pathways in mammalian cells. An examination of this research, with emphasis on the function of checkpoint proteins, their relationship to DNA repair, and their involvement in oncogenesis is undertaken here. Christine Latif, Susan H. Harvey, and Susan J. O'Connell Copyright © 2001 Christine Latif et al. All rights reserved. Publication of a Special Issue: Gene Dosage Effect During Embryonic Development Mon, 01 Jan 1900 00:00:00 +0000 Claire Redhead Copyright © 2007 Claire Redhead. All rights reserved. Effects of Pesticides on Occupationally Exposed Humans Mon, 01 Jan 1900 00:00:00 +0000 Pesticides are known to contain numerous genotoxic compounds; however, genotoxicity biomonitoring studies of workers occupationally exposed to pesticides have produced variable results. In this study, we employed the Comet assay to examine DNA damage in peripheral blood lymphocytes (PBLs) from 64 greenhouse workers from Almería in south-eastern Spain in comparison to PBLs from 50 men from the same area but not engaged in any agricultural work. The results indicated that there were no differences in the basal levels of DNA damage in the two study groups. In addition, exposure of PBL from the workers and controls to hydrogen peroxide or γ-irradiation led to similar levels of DNA damage; the subsequent repair of the induced DNA damage was also similar for both study populations. Smoking had no impact on any of the responses. The results of this study indicate that the greenhouse workers had no detectable increase in DNA damage or alteration in the cellular response to DNA damage compared to our control population. Stylianos M. Piperakis, Konstantina Kontogianni, Michael M. Piperakis, Ricardo Marcos, and Smaragdi Tsilimigaki Copyright © 2006 Stylianos M. Piperakis et al. All rights reserved. Genetic Control of Programmed Cell Death in C. Elegans Mon, 01 Jan 1900 00:00:00 +0000 H. Robert Horvitz Copyright © 2001 H. Robert Horvitz. All rights reserved. Chronic Alcohol Consumption Attenuates Apoptosis by Down Regulation of P53 Expression in the Rat Pancreas Mon, 01 Jan 1900 00:00:00 +0000 Franco Fortunato and Lawrence K. Gates Jr. Copyright © 2001 Franco Fortunato and Lawrence K. Gates Jr.. All rights reserved. Genetics of Early-Onset Alzheimer Dementia Mon, 01 Jan 1900 00:00:00 +0000 Alzheimer�s dementia (AD) is the most common degenerative disorder of the central nervous system. Although the onset of dementia is above 65 years of age in the majority of the patients (late-onset AD, LOAD), a small subgroup of patients develops AD before 65 years of age (early-onset AD, EOAD). To date 3 genes responsible for EOAD have been identified: the amyloid precursor protein gene (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). PSEN1 is the most frequently mutated EOAD gene with a mutation frequency of 18 to 50% in autosomal dominant EOAD. In addition, the e4 allele of the gene encoding apolipoprotein E (APOE) was identified as a risk factor for both LOAD and EOAD. Many studies reported other susceptibility genes, but the APOE?4 alelle has been the only risk factor that was consistently replicated in all AD populations. Extensive cell biology research in the past ten years led to the hypothesis that the 4 EOAD genes lead to AD through a common biological pathway resulting in abnormal APP processing by subtle different mechanisms. Now, transgenic mice are produced to study the influence of EOAD mutations in vivo, eventually leading to the development of novel therapeutic strategies. Rosa Rademakers, Marc Cruts, and Christine Van Broeckhoven Copyright © 2003 Rosa Rademakers et al. All rights reserved. Decoding Drug Abuse in Noncoding RNA? Mon, 01 Jan 1900 00:00:00 +0000 Da-Yu Wu and John S. Saterlee Copyright © 2007 Da-Yu Wu and John S. Saterlee. All rights reserved. The DNA Polymerase _-Primase Complex: Multiple Functions and Interactions Mon, 01 Jan 1900 00:00:00 +0000 DNA polymerase _ (pol _) holds a special position among the growing family of eukaryotic DNA polymerases. In fact, pol _ is associated with DNA primase to form a four subunit complex and, as a consequence, is the only enzyme able to start DNA synthesis de novo. Because of this peculiarity the major role of the DNA polymerase _-primase complex (pol-prim) is in the initiation of DNA replication at chromosomal origins and in the discontinuous synthesis of Okazaki fragments on the lagging strand of the replication fork. However, pol-prim seems to play additional roles in other complex cellular processes, such as the response to DNA damage, telomere maintenance, and the epigenetic control of higher order chromatin assembly. Marco Muzi-Falconi, Michele Giannattasio, Marco Foiani, and Paolo Plevani Copyright © 2003 Marco Muzi-Falconi et al. All rights reserved. Genotoxic and antigenotoxic properties of selenium compounds in the in vitro micronucleus assay with human whole blood lymphocytes and tk6 lymphoblastoid cells Mon, 01 Jan 1900 00:00:00 +0000 Selenium is known to possess both genotoxic and antigenotoxic properties. In the present study, we have evaluated the genotoxicity and antigenotoxicity of three selenium compounds (sodium selenate, sodium selenite and selenous acid) by measuring in vitro micronucleus induction. Assays were conducted in whole blood lymphocytes and in the TK6 lymphoblastoid cell line, with and without co-treatment with potassium dichromate, a known genotoxic compound. In general, the compounds were more active in TK6 cells than they were in blood lymphocytes. Only 1 μM selenous acid increased the frequency of binucleated cells containing micronuclei (BNMN) in blood lymphocytes, while all three selenium compounds increased BNMN in TK6 cells. In addition, combinations of selenous acid and potassium dichromate resulted in lower frequencies of BNMN than potassium dichromate alone in blood lymphocytes, while combinations of sodium selenate and potassium dichromate produced lower frequencies of BNMN than potassium dichromate alone in TK6 cells. The concentrations of selenium compounds that were used, in combination with the medium components and the biological physiology of the whole blood lymphocytes and TK6 cells, could have affected the redox potential of the compounds, switching the chemicals from a pro-oxidant to antioxidant status and vice-versa. The lower activities of the compounds in blood lymphocytes may be due to the protective effects of blood components. The results indicate that the genotoxic and antigenotoxic properties of selenium compounds are highly dependent upon the conditions under which they are evaluated. Eduard Cemeli, Ricard Marcos, and Diana Anderson Copyright © 2006 Eduard Cemeli et al. All rights reserved. Inhibition of Apoptosis by the BEACH Domain and WD Repeats of Gene lba that has Key Features of Both Protein Kinase A Anchor and chs1/beige Genes Mon, 01 Jan 1900 00:00:00 +0000 Jia-Wang Wang, Julie Howson, Tomar Ghansah, John Ninos, and William G. Kerr Copyright © 2001 Jia-Wang Wang et al. All rights reserved. DNA Polymerase Gamma in Mitochondrial DNA Replication and Repair Mon, 01 Jan 1900 00:00:00 +0000 Mutations in mitochondrial DNA (mtDNA) are associated with aging, and they can cause tissue degeneration and neuromuscular pathologies known as mitochondrial diseases. Because DNA polymerase γ (pol γ) is the enzyme responsible for replication and repair of mitochondrial DNA, the burden of faithful duplication of mitochondrial DNA, both in preventing spontaneous errors and in DNA repair synthesis, falls on pol γ. Investigating the biological functions of pol γ and its inhibitors aids our understanding of the sources of mtDNA mutations. In animal cells, pol γ is composed of two subunits, a larger catalytic subunit of 125–140 kDa and second subunit of 35–55 kDa. The catalytic subunit contains DNA polymerase activity, 3’-5’ exonuclease activity, and a 5’-dRP lyase activity. The accessory subunit is required for highly processive DNA synthesis and increases the affinity of pol gamma to the DNA. William C. Copeland and Matthew J. Longley Copyright © 2003 William C. Copeland and Matthew J. Longley. All rights reserved. Inhibition of Human Telomerase Reverse Transcritpase (hTERT) and Telomerase Activity by Curcumin in Human Mammary Epithelial and Breast Carcinoma Cell Lines Mon, 01 Jan 1900 00:00:00 +0000 Chappail Ramachandran, Hugo B. Fonseca, Perseus Jhabvala, Steven J. Melnick, and Enrique Escalon Copyright © 2001 Chappail Ramachandran et al. All rights reserved. Calcitonin Gene-Related Peptide in Tension-Type Headache Mon, 01 Jan 1900 00:00:00 +0000 Messoud Ashina Copyright © 2001 Messoud Ashina. All rights reserved. Endogenous Receptor Agonists: Resolving Inflammation Mon, 01 Jan 1900 00:00:00 +0000 Controlled resolution or the physiologic resolution of a well-orchestrated inflammatory response at the tissue level is essential to return to homeostasis. A comprehensive understanding of the cellular and molecular events that control the termination of acute inflammation is needed in molecular terms given the widely held view that aberrant inflammation underlies many common diseases. This review focuses on recent advances in the understanding of the role of arachidonic acid and ω-3 polyunsaturated fatty acids (PUFA)–derived lipid mediators in regulating the resolution of inflammation. Using a functional lipidomic approach employing LC-MS-MS–based informatics, recent studies, reviewed herein, uncovered new families of local-acting chemical mediators actively biosynthesized during the resolution phase from the essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These new families of local chemical mediators are generated endogenously in exudates collected during the resolution phase, and were coined resolvins and protectins because specific members of these novel chemical families control both the duration and magnitude of inflammation in animal models of complex diseases. Recent advances on the biosynthesis, receptors, and actions of these novel anti-inflammatory and proresolving lipid mediators are reviewed with the aim to bring to attention the important role of specific lipid mediators as endogenous agonists in inflammation resolution. Gerhard Bannenberg, Makoto Arita, and Charles N. Serhan Copyright © 2007 Gerhard Bannenberg et al. All rights reserved. Intracellular Targeting of CEA Results in Th1-Type Antibody Responses Following Intradermal Genetic Vaccination by a Needle-Free Jet Injection Device Mon, 01 Jan 1900 00:00:00 +0000 The route and method of immunization, as well as the cellular localization of the antigen, can influence the generation of an immune response. In general, intramuscular immunization results in Th1 responses, whereas intradermal delivery of DNA by gene gun immunization often results in more Th2 responses. Here we investigate how altering the cellular localization of the tumor antigen CEA (carcinoembryonic antigen) affects the quality and amplitude of DNA vaccine-induced antibody responses in mice following intradermal delivery of DNA by a needle-free jet injection device (Biojector). CEA was expressed either in a membrane-bound form (wild-type CEA) or in two truncated forms (CEA6 and CEA66) with cytoplasmic localization, where CEA66 was fused to a promiscuous T-helper epitope from tetanus toxin. Repeated intradermal immunization of BALB/c mice with DNA encoding wild-type CEA produced high antibody titers of a mixed IgG1/IgG2a ratio. In contrast, utilizing the DNA construct that resulted in intracellular targeting of CEA led to a reduced capacity to induce CEA-specific antibodies, but instead induced a Th1-biased immune response. Susanne Johansson, Monica Ek, Britta Wahren, Richard Stout, Margaret A. Liu, and Kristian Hallermalm Copyright © 2007 Susanne Johansson et al. All rights reserved. Association between 45T/G Polymorphism of Adiponectin Gene and Coronary Artery Disease in an Iranian Population Mon, 01 Jan 1900 00:00:00 +0000 A single nucleotide polymorphism (SNP) in the adiponectin gene, 45T/G, has been reported in relation to a number of metabolic disorders, including obesity, insulin resistance, and diabetes. However, previous studies on the association between this SNP and the presence of coronary artery disease (CAD) have been few, with no report from Iranian subjects. The present study set out to investigate the association between this SNP and CAD in an Iranian population. Among 464 patients (age: 18–75 years), recruited from individuals who underwent coronary angiography, 135 patients had less than 50% reduction of coronary artery diameter and were classified as the CAD- group and 329 patients had more than 50% reduction of coronary artery diameter and were classified as the CAD+ group. The last group was divided into single-vessel disease (n = 86), two-vessel disease (n = 111), and three-vessel disease (n = 132). Healthy subjects (n = 106) who did not have any history of heart diseases were also recruited as the control group. All subjects were genotyped for the 45T/G polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. A significantly higher frequency of the TG genotype and G allele, which was paralleled by a lower frequency of the TT genotype and T allele, was observed in both CAD+ and CAD- patients when compared with the control group (p ≤ 0.001). There was no significant difference in the genotype distribution and allele frequencies between CAD+ and CAD- patients, and also between different subgroups of patients based on the number of stenosed vessels (p > 0.05). Our findings indicate that the presence of the G allele at the position +45 of the adiponectin gene may be associated with the risk of CAD in our study population. While we found no significant difference in the genotype distribution and allele frequencies between patients with angiography+ and angiography, this may be because the 50% stenosis cut-off does not discriminate sufficiently between individuals with and without significant coronary disease. Somaye Sabouri, Majid Ghayour Mobarhan, Mohsen Moohebati, Mitra Hassani, Jamal Kassaeian, Farnoosh Tatari, Fatemeh Mahmoodi-kordi, Habib A. Esmaeili, Shima Tavallaie, Roghayeh Paydar, Amirhossein Sahebkar, Shahireh Omidvar Tehrani, Gordon Ferns, and Javad Behravan Copyright © 2011 Somaye Sabouri et al. All rights reserved. Involvement of the Gli3 (Extra-Toes) Gene Region in Body Weight in Mice Mon, 01 Jan 1900 00:00:00 +0000 The mutation extra-toes (Gli3Xt-J) on chromosome (Chr) 13 of the mouse is known to be involved in the development of the skeleton. The only visible manifestation is the presence of an extra digit on each hind foot. Here we report evidence from several experiments that Gli3XtJ/+ mice weigh more than littermate Gli3+/+ mice, suggesting an effect on body weight of Gli3 or of a gene tightly linked to it on Chr 13. Four independent experiments in different environments were conducted on mice with different genetic backgrounds derived from the C3XtEso Gli3Xt-J/+ Eso/+ linkage testing strain and the JE/Le strain at adult age. The analyses have shown an association between the Gli3Xt-J allele and a body weight increase of about 6.5%. This effect is genetically dominant. It would appear that if the gene of interest is not Gli3 itself, it must be very close to this locus. Indeed, the expected size for this fragment is 7.9 ± 5.3 cM. The manifestation of this gene, observed in two animal facilities and on different genetic backgrounds, is consistent with the idea that the effect of the gene(s) is displayed in a stable manner. It accounts for a variation of 6.5% of body weight. Benoît Martin, Eve Lapouble, and Yohan Chaix Copyright © 2007 Benoît Martin et al. All rights reserved. Genetic Damage Induced by Accidental Environmental Pollutants Mon, 01 Jan 1900 00:00:00 +0000 Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world, Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC), and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE), micronucleus (MN) test, and comet assay. Four groups of individuals were included: volunteers (V), hired manual workers (MW), hired high-pressure cleaner workers (HPW) and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate. Beatriz Pérez-Cadahía, Blanca Laffon, Eduardo Pásaro, and Josefina Méndez Copyright © 2006 Beatriz Pérez-Cadahía et al. All rights reserved. Differential Micronuclei Induction in Human Lymphocyte Cultures by Imidacloprid in the Presence of Potassium Nitrate Mon, 01 Jan 1900 00:00:00 +0000 Humans are exposed to pesticides as a consequence of their application in farming or their persistence in a variety of media, including food, water, air, soil, plants, animals, and smoke. The interaction of pesticides with environmental factors may result in the alteration of their physicochemical properties. Square wave cathodic stripping voltammetry (SW-CSV), a technique that simulates electrodynamically the cellular membrane, is used to investigate whether the presence of potassium nitrate (KNO3) in the culture medium interferes with the genotoxic behavior of imidacloprid. The cytokinesis block micronuclei (CBMN) method is used to evaluate imidacloprid's genotoxicity in the absence or presence of KNO3 in the culture medium and, as a consequence, its adsorption by lymphocytes. Comparing micronuclei (MN) frequencies in control and imidacloprid-treated blood cell cultures, statistically significant differences were not detected. KNO3 did not induce MN frequencies compared to control. Statistically significant differences in MN frequencies were observed when blood cell cultures were treated with imidacloprid in the presence of increasing concentrations of KNO3. SW-CSV revealed that by increasing KNO3 molarity, imidacloprid's concentration in the culture medium decreased in parallel. This finding indicates that imidacloprid is adsorbed by cellular membranes. The present study suggests a novel role of a harmless environmental factor, such as KNO3, on the genotoxic behavior of a pesticide, such as imidacloprid. KNO3 rendered imidacloprid permeable to lymphocytes, resulting in elevated MN frequencies. Polychronis Stivaktakis, Dimitris Vlastos, Evangelos Giannakopoulos, and Demetrious P. Matthopoulos Copyright © 2010 Polychronis Stivaktakis et al. All rights reserved. Identification and Sequencing of Bcl and Apaf1 Genes in the Common Carp, Cyprinus Carpio Mon, 01 Jan 1900 00:00:00 +0000 C. Chakravarthy, G.T. Williams, and D. Hoole Copyright © 2001 C. Chakravarthy et al. All rights reserved. MicroRNA Profiling: From Dark Matter to White Matter, or Identifying New Players in Neurobiology Mon, 01 Jan 1900 00:00:00 +0000 Contemporary biology has been revolutionized by a recently discovered class of small regulatory RNA molecules, microRNAs (miRNAs). Missed by researchers for decades due to their tiny size, usually mapping to non-protein-coding regions of genomes, miRNAs and miRNA-mediated regulatory networks have been the “dark matter” of molecular biology. Deciphering miRNA pathways and functions in the CNS of complex organisms is tightly linked to understanding miRNA expression patterns. To facilitate these emerging studies, I here review the basic principles of medium- and high-throughput technologies available for miRNA expression profiling. Anna M. Krichevsky Copyright © 2007 Anna M. Krichevsky. All rights reserved. Involvement and Therapeutic Potential of the GABAergic System in the Fragile X Syndrome Mon, 01 Jan 1900 00:00:00 +0000 Many drugs have been developed that are able to modulate the GABAergic system, which is involved in anxiety, depression, epilepsy, insomnia, and learning and memory. The recent observation that the GABAA receptor is underexpressed in the fragile X syndrome, an inherited mental retardation disorder, therefore raised hopes for targeted therapy of the disorder. This review summarizes the lines of evidence that demonstrate a malfunction of the GABAergic system. The GABAergic system clearly emerges as an attractive target for therapy of the fragile X syndrome, and thus provides an excellent example of how genetic research can lead to unique opportunities for treatment. Inge Heulens, Charlotte D'Hulst, Sien Braat, Liesbeth Rooms, and R. Frank Kooy Copyright © 2010 Inge Heulens et al. All rights reserved. Susceptibility to Aneuploidy in Young Mothers of Down Syndrome Children Mon, 01 Jan 1900 00:00:00 +0000 We recently observed an increased frequency of binucleated micronucleated lymphocytes in women who had a Down syndrome (DS) child before 35 years of age and the fluorescence in situ hybridization analysis revealed that micronuclei were mainly originating from chromosomal malsegregation events, including chromosome 21 malsegregation. That study indicated that women who have a DS child at a young age might have a genetic predisposition to chromosome malsegregation in both somatic and germ line cells. Further studies from our group confirmed increased chromosome damage in blood cells of women who had a DS child at a young age and pointed to a possible role for polymorphisms in folate-metabolizing genes in affecting both chromosome damage and DS risk. In the present article, we review the most recent findings on mechanisms and risk factors for chromosome 21 nondisjunction that lead to DS. Multiple risk factors are likely involved in chromosome nondisjunction; they act at different times in the meiotic process and can be of genetic or environmental (epigenetic) origin. We also discuss the increased risk of developing Alzheimer's disease (AD) later in life that was observed in women who had a DS child at a young age. Studies performed in the last years that have shown that the brain is, in fact, a complex genetic mosaic of aneuploid and euploid cells support the unified hypothesis trying to relate DS, trisomy 21, and AD. Lucia Migliore, Francesca Migheli, and Fabio Coppedè Copyright © 2009 Lucia Migliore et al. All rights reserved. Sickle Cell Anemia, the First Molecular Disease: Overview of Molecular Etiology, Pathophysiology, and Therapeutic Approaches Mon, 01 Jan 1900 00:00:00 +0000 The root cause of sickle cell disease is a single β-globin gene mutation coding for the sickle β-hemoglobin chain. Sickle hemoglobin tetramers polymerize when deoxygenated, damaging the sickle erythrocyte. A multifaceted pathophysiology, triggered by erythrocyte injury induced by the sickle hemoglobin polymer, and encompassing more general cellular and tissue damage caused by hypoxia, oxidant damage, inflammation, abnormal intracellular interactions, and reduced nitric oxide bioavailability, sets off the events recognized clinically as sickle cell disease. This disease is a group of related disorders where sickle hemoglobin is the principal hemoglobin species. All have varying degrees of chronic hemolytic anemia, vasculopathy, vasoocclusive disease, acute and chronic organ damage, and shortened life span. Its complex pathophysiology, of which we have a reasonable understanding, provides multiple loci for potential therapeutic intervention. Martin H. Steinberg Copyright © 2008 Martin H. Steinberg. All rights reserved. The Physiology of Obese-Hyperglycemic Mice [ob/ob Mice] Mon, 01 Jan 1900 00:00:00 +0000 This review summarizes key aspects of what has been learned about the physiology of leptin deficiency as it can be observed in obese-hyperglycemic ob/ob mice. These mice lack functional leptin. They are grossly overweight and hyperphagic, particularly at young ages, and develop severe insulin resistance. They have been used as a model for obesity and as a rich source of pancreatic islets with high insulin release capacity. The leptin deficiency manifests also with regard to immune function, the cardiovascular system including angiogenesis, supportive tissue function, malignancies, and reproductive function. ob/ob Mice are well suited for studies on the interaction between leptin and insulin, and for studies on initial aspects of metabolic disturbances leading to type-2diabetes. Per Lindström Copyright © 2007 Per Lindström. All rights reserved. Genomic Imprinting and Cancer: From Primordial Germ Cells to Somatic Cells Mon, 01 Jan 1900 00:00:00 +0000 Imprinted genes are a subset of genes that are expressed from only one of the parental alleles. The majority of imprinted genes have roles in growth regulation and are, therefore, potential oncogenes or tumour suppressors. Cancer is a disease of aberrant cell growth and is characterised by genetic mutations and epigenetic changes such as DNA methylation. The mechanisms whereby imprinting is maintained in somatic cells and then erased and reset in the germline parallels epigenetic changes that cancer cells undergo. This review summarises what we know about imprinting in stem cells and how loss of imprinting may contribute to neoplasia. Adele Murrell Copyright © 2006 Adele Murrell. All rights reserved. The use of premature chromosome condensation to study in interphase cells the influence of environmental factors on human genetic material Mon, 01 Jan 1900 00:00:00 +0000 Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics) and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC) induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics. Vasiliki I. Hatzi, Georgia I. Terzoudi, Christina Paraskevopoulou, Vasilios Makropoulos, Demetrios P. Matthopoulos, and Gabriel E. Pantelias Copyright © 2006 Vasiliki I. Hatzi et al. All rights reserved. PDZ and LIM Domain-Encoding Genes: Molecular Interactions and their Role in Development Mon, 01 Jan 1900 00:00:00 +0000 PDZ/LIM genes encode a group of proteins that play very important, but diverse, biological roles. They have been implicated in numerous vital processes, e.g., cytoskeleton organization, neuronal signaling, cell lineage specification, organ development, and oncogenesis. Aartjan J. W. te Velthuis and Christoph P. Bagowski Copyright © 2007 Aartjan J. W. te Velthuis and Christoph P. Bagowski. All rights reserved. Clinical Profiles, Occurrence, and Management of Adolescent Patients with HAIR-AN Syndrome Mon, 01 Jan 1900 00:00:00 +0000 The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) is a subphenotype of the polycystic ovary syndrome. It is one of the most common causes of menstrual problems, hyperandrogenic symptoms, and insulin resistance among young women. Review of clinical data in an outpatient adolescent clinic showed that of the 1,002 young women (ages 10—21 years) attending the clinic over a 2-year period, 50 (5%) were diagnosed with HAIR-AN syndrome. Mean age of the patients was 15.5, initial mean weight at diagnosis was 94.5 kg, and the mean BMI was 33.33 kg/m2. Patients were treated with a weight-stabilization and -reduction program, oral contraceptive pills, and in most cases metformin. Of the patients, 80% were compliant with the follow-up and treatment regimen, 60% maintained or reduced their weight, 95% had regular menstrual cycles, and in most patients, the acne and/or hirsutism were the same or better than at the start of treatment. We conclude that HAIR-AN syndrome is a common disease in young women and multifaceted, aggressive treatment appears to be effective in reducing the severity of symptoms and preventing further consequences. Hatim A. Omar, Stephanie Logsdon, and Jessica Richards Copyright © 2004 Hatim A. Omar et al. All rights reserved. Simultaneous Penile and Signet Ring Cell Bladder Carcinoma in Renal Transplant Recipient: A First Case Mon, 01 Jan 1900 00:00:00 +0000 The incidence and prevalence of cancer increase with time after transplantation. Therefore, a risk-adapted screening process is very important in order to identify low-grade malignancies early in their development. This provides the opportunity to initiate appropriate immunosuppressive regimens depending on the tumor type and stage of development. The first case presented is one of a 65-year-old patient with a double genitourinary carcinoma (penis and bladder). The patient received kidney transplantation 7 years prior to this event. After adequate surgical treatment (partial amputation of the penis for squamous cell carcinoma and complete transurethral resection of bladder adenocarcinoma), the patient was noted to be free of tumor recurrence and had functioning renal graft with a 2-year follow-up. Francesca Manassero, Gianluca Giannarini, Davide Paperini, Andrea Mogorovich, Greta Alí, Ugo Boggi, and Cesare Selli Copyright © 2009 Francesca Manassero et al. All rights reserved. Symbiotic Gene Activation is Interrupted by Endocrine Disrupting Chemicals Mon, 01 Jan 1900 00:00:00 +0000 Endocrine disrupting chemicals (EDCs) include organochlorine pesticides, plastics manufacturing by-products, and certain herbicides[1]. These chemicals have been shown to disrupt hormonal signaling in exposed wildlife, lab animals, and mammalian cell culture by binding to estrogen receptors (ER-α and ER-β) and affecting the expression of estrogen responsive genes[2,3]. Additionally, certain plant chemicals, termed phytoestrogens, are also able to bind to estrogen receptors and modulate gene expression, and as such also may be considered EDCs[4]. One example of phytoestrogen action is genistein, a phytochemical produced by soybeans, binding estrogen receptors, and changing expression of estrogen responsive genes which certain studies have linked to a lower incidence of hormonally related cancers in Japanese populations[5]. Why would plants make compounds that are able to act as estrogens in the human body? Obviously, soybeans do not intentionally produce phytoestrogens to prevent breast cancer in Japanese women. Jennifer E. Fox, Matthew E. Burow, and John A. McLachlan Copyright © 2001 Jennifer E. Fox et al. All rights reserved. Repeated Salmon Calcitonin Injection Lowers Body Weight and Body Fat Mon, 01 Jan 1900 00:00:00 +0000 T. A. Lutz, P. A. Rushing, and T. Riediger Copyright © 2001 T.A. Lutz et al. All rights reserved. Evaluation of Stature Development During Childhood and Adolescence in Individuals with Familial Hypophosphatemic Rickets Mon, 01 Jan 1900 00:00:00 +0000 This review was conducted to study the diagnosis, treatment, and growth progression in infants and adolescents with familial hypophosphatemic rickets. The bibliographic search was carried out utilizing the electronic databases MEDLINE, OVID, and LILACS and by direct research within the last 15 years using the keywords rickets, familial hypophosphatemia, vitamin D deficiency, stature growth, childhood, and adolescence. Article selection was done by comparing the evaluation of the growth in patients with familial hypophosphatemic rickets, including the variables that might affect them, for possible future therapeutic proposals. It is concluded that the most significant fact in the treatment of familial hypophosphatemic rickets in infancy was the magnitude of the final stature. The use of growth hormone can be helpful in these patients. However, research reporting treatments with the use of the growth hormone for rickets are controversial. The majority of the authors agree that treatment using vitamin D and phosphate enables some statural growth in cases of early diagnosis, reflecting a better prognosis. Mauro M.S. Borghi, Veronica Coates, and Hatim A. Omar Copyright © 2005 Mauro M.S. Borghi et al. All rights reserved. Aging in Persons with Rett Syndrome: An Updated Review Mon, 01 Jan 1900 00:00:00 +0000 Rett syndrome (RS) is a neurological disease affecting mainly females, characterized by an arrest of brain development caused by an X-linked mutation. Rett syndrome is the first human disease found to be caused by defects in a protein involved in regulating gene expression through its interaction with methylated DNA. The disease has been traced to a defective gene called MECP2. The case stories presented here and recent findings show that females with RS are able to live into old age. Due to the observed longevity of individuals with RS, and the fact that individuals with RS present the therapist/physician with specific clinical challenges, it is suggested that proper, long-term, and individually tailored, intensive care should be provided at all ages in the hope to prevent or at least reduce the age-related deterioration that is typical of this population. Meir Lotan, Joav Merrick, Isack Kandel, and Mohammed Morad Copyright © 2010 Meir Lotan et al. All rights reserved. CGRP in Primary Headaches Mon, 01 Jan 1900 00:00:00 +0000 Lars Edvinsson Copyright © 2001 Lars Edvinsson. All rights reserved. Mitochondrial Genes in Degenerative Disease and Aging Mon, 01 Jan 1900 00:00:00 +0000 Douglas C. Wallace Copyright © 2001 Douglas C. Wallace. All rights reserved. miR-126 and miR-126*: New Players in Cancer Mon, 01 Jan 1900 00:00:00 +0000 Cancer progression is characterized by autarky in growth signals, insensitivity to growth-restrictive signals, evasion of apoptosis, a limitless potential to replicate, sustained angiogenesis, and tissue invasion, including metastasis. The regulation of these cellular processes relies on a fine-tuned control of molecular signal cascades. In recent years, short noncoding RNAs termed microRNAs (miRNAs) have been described as a novel class of molecular regulators. These affect various signaling cascades during the progression of neoplastic diseases by the regulation of gene expression on the post-transcriptional level. The novel endothelial cell–derived secreted protein epidermal growth factor–like domain 7 (EGFL7) has been suggested to control vascular tubulogenesis. Further, the two biologically active miRNAs miR-126 and its complement miR-126*, which are encoded by intron 7 of the egfl7 gene, have been described to mediate vascular functions. Knock-out studies in zebrafish and mice suggested a major role of miR-126 in angiogenesis and vascular integrity, which was mediated by the repression of inhibitors of VEGF-induced proliferation in endothelial cells. Recent studies revealed the distribution and function of miR-126 and miR-126* in various types of cancer, and assigned a role to both miRNAs as suppressors of tumor formation. Indeed, miR-126 and miR-126* have been reported to impair cancer progression through signaling pathways that control tumor cell proliferation, migration, invasion, and survival. Conversely, miR-126 and miR-126* may have a supportive role in the progression of cancer as well, which might be mediated by the promotion of blood vessel growth and inflammation. In this work, we will summarize the current knowledge on functions of miR-126/miR-126* that are relevant for cancer formation, and we will discuss their potential clinical use as predictive markers of survival and application as novel therapeutic targets for the treatment of neoplastic diseases. Jeannette Meister and Mirko H. H. Schmidt Copyright © 2010 Jeannette Meister and Mirko H. H. Schmidt. All rights reserved. Establishment of Okadaic Acid Resistant Cell Clones using CDNA Library Expression Cloning Mon, 01 Jan 1900 00:00:00 +0000 Tone Sandal, Johan Lillehaug, Stein Ove D skeland, and Ragnhild Ahlgren Copyright © 2001 Tone Sandal et al. All rights reserved. The 22q11.2 Deletion Syndrome: A Gene Dosage Perspective Mon, 01 Jan 1900 00:00:00 +0000 The 22q11.2 deletion/DiGeorge syndrome is a relatively common “genomic” disorder that results from heterozygous deletion of a 3-Mbp segment of chromosome 22. Of the more than 30 genes deleted in this syndrome, TBX1 is the only one that has been found to be mutated in some patients with a phenotype that is very similar to that of patients with the full deletion, suggesting that TBX1 haploinsufficiency is a major contributor to the syndrome’s phenotype. Multi- and single-gene mouse models have provided a considerable amount of information about the consequences of decreased and increased dosage of the genomic region (and in particular of the Tbx1 gene) on mouse embryonic development. Modified alleles of Tbx1, as well as conditional ablation strategies have been utilized to map in vivo the tissues and developmental stages most sensitive to gene dosage. These experiments have revealed substantially different sensitivity to gene dosage in different tissues and at different times, underlying the importance of the developmental context within which gene dosage reduction occurs. Antonio Baldini Copyright © 2006 Antonio Baldini. All rights reserved. The Mechanism of RNA Interference and the Transposon Silencing in Caenorhabditis elegans Mon, 01 Jan 1900 00:00:00 +0000 Marcel Tijsterman, Rena Ketting, Sylvia Fischer, Femke Simmer, Titia Sijen, Kristy Okihara, Bas Tops, Nadine Vastenhouw, and Ronald Plasterk Copyright © 2002 Marcel Tijsterman et al. All rights reserved. Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes Mon, 01 Jan 1900 00:00:00 +0000 The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA), identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA. David Goldman and Francesca Ducci Copyright © 2007 David Goldman and Francesca Ducci. All rights reserved. The Effect of Calcitonin Gene-Related Peptide (CGRP) on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries Mon, 01 Jan 1900 00:00:00 +0000 The aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i) was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analogue U46619) and with high concentration of extracellular potassium. At a steady state of contraction, the increase in [Ca2+]i induced by 300 nM U46619 (100״x 14 nM, n = 7) was similar to that induced by 36 mM K+ (98 ״x 9 nM, n = 7). However, the active tension induced by 300 nM U46619 was significantly (p < 0.01) higher than that induced by 36 mM K+. CGRP concentration-dependently (10 pM - 10 nM) reduced both the [Ca2+]i and tension of coronary arteries precontracted with either U46619 or BAY K 8644, and also of resting coronary arteries in PSS. In 36 mM K+-depolarized arteries, CGRP reduced only the tension without affecting the [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with 10 μM thapsigargin significantly (p < 0.05) attenuated the CGRP-induced reduction in the tension (but not [Ca2+]i). In 300 nM U46619 precontracted arteries, pretreatment with either 100 nM charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (p < 0.05) attenuated the CGRP-induced reduction in both [Ca2+]i and the tension. In contrast, 1 μM glibenclamide did not affect the CGRP-induced responses in these coronary arteries. In resting coronary arteries, only pretreatment with the combination of 1 μM glibenclamide and 100 nM charybdotoxin attenuated the CGRP-induced decrease in the [Ca2+]i and tension, suggesting a different mechanism of action for CGRP in resting coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1) a decrease in [Ca2+]i by inhibiting the Ca2+ influx through membrane hyperpolarization mediated partly by activation of BKCa channels, (2) a decrease in [Ca2+]i presumably by sequestrating cytosolic Ca2+ into thapsigargin-sensitive Ca2+ storage sites, and (3) a decrease in the Ca2+ -sensitivity of the contractile apparatus. M. Sheykhzade and N.C.B. Nyborg Copyright © 2001 M. Sheykhzade and N.C.B. Nyborg. All rights reserved. Induction of Golli-MBP Expression in CNS Macrophages During Acute LPS-Induced CNS Inflammation and Experimental Autoimmune Encephalomyelitis (EAE) Mon, 01 Jan 1900 00:00:00 +0000 Microglia are the tissue macrophages of the CNS. Microglial activation coupled with macrophage infiltration is a common feature of many classic neurodegenerative disorders. The absence of cell-type specific markers has confounded and complicated the analysis of cell-type specific contributions toward the onset, progression, and remission of neurodegeneration. Molecular screens comparing gene expression in cultured microglia and macrophages identified Golli-myelin basic protein (MBP) as a candidate molecule enriched in peripheral macrophages. In situ hybridization analysis of LPS/IFNg and experimental autoimmune encephalomyelitis (EAE)–induced CNS inflammation revealed that only a subset of CNS macrophages express Golli-MBP. Interestingly, the location and morphology of Golli-MBP+ CNS macrophages differs between these two models of CNS inflammation. These data demonstrate the difficulties of extending in vitro observations to in vivo biology and concretely illustrate the complex heterogeneity of macrophage activation states present in region- and stage-specific phases of CNS inflammation. Taken altogether, these are consistent with the emerging picture that the phenotype of CNS macrophages is actively defined by their molecular interactions with the CNS microenvironment. Tracey L. Papenfuss, J. Cameron Thrash, Patricia E. Danielson, Pamela E. Foye, Brian S. Hllbrush, J. Gregor Sutcliffe, Caroline C. Whitacre, and Monica J. Carson Copyright © 2007 Tracey L. Papenfuss et al. All rights reserved. Influence of Poly(L-Lactic Acid) Nanofibers and BMP-2–Containing Poly(L-Lactic Acid) Nanofibers on Growth and Osteogenic Differentiation of Human Mesenchymal Stem Cells Mon, 01 Jan 1900 00:00:00 +0000 The aim of this study was to characterize synthetic poly-(L-lactic acid) (PLLA) nanofibers concerning their ability to promote growth and osteogenic differentiation of stem cells in vitro, as well as to test their suitability as a carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2–incorporated PLLA were seeded with human mesenchymal stem cells and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and collagen I (COL-I). Furthermore, COL-I and OC deposition, as well as cell densities and proliferation, were analyzed using fluorescence microscopy. Although the presence of nanofibers diminished the dexamethasone-induced proliferation, there were no differences in cell densities or deposition of either COL-I or OC after 22 days of culture. The gene expression of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA nanofibers as compared to cover slip control, but normalized during the course of cultivation. The initial down-regulation was not observed when BMP-2 was directly incorporated into PLLA nanofibers by electrospinning, indicating that growth factors like BMP-2 might survive the spinning process in a bioactive form. Markus D. Schofer, Susanne Fuchs-Winkelmann, Christian Gräbedünkel, Christina Wack, Roland Dersch, Markus Rudisile, Joachim H. Wendorff, Andreas Greiner, Jürgen R. J. Paletta, and Ulrich Boudriot Copyright © 2008 Markus D. Schofer et al. All rights reserved. Molecular Detection of Bladder Cancer by Fluorescence Microsatellite Analysis and an Automated Genetic Analyzing System Mon, 01 Jan 1900 00:00:00 +0000 To investigate the ability of an automated fluorescent analyzing system to detect microsatellite alterations, in patients with bladder cancer. We investigated 11 with pathology proven bladder Transitional Cell Carcinoma (TCC) for microsatellite alterations in blood, urine, and tumor biopsies. DNA was prepared by standard methods from blood, urine and resected tumor specimens, and was used for microsatellite analysis. After the primers were fluorescent labeled, amplification of the DNA was performed with PCR. The PCR products were placed into the automated genetic analyser (ABI Prism 310, Perkin Elmer, USA) and were subjected to fluorescent scanning with argon ion laser beams. The fluorescent signal intensity measured by the genetic analyzer measured the product size in terms of base pairs. We found loss of heterozygocity (LOH) or microsatellite alterations (a loss or gain of nucleotides, which alter the original normal locus size) in all the patients by using fluorescent microsatellite analysis and an automated analyzing system. In each case the genetic changes found in urine samples were identical to those found in the resected tumor sample. The studies demonstrated the ability to detect bladder tumor non-invasively by fluorescent microsatellite analysis of urine samples. Our study supports the worldwide trend for the search of non-invasive methods to detect bladder cancer. We have overcome major obstacles that prevented the clinical use of an experimental system. With our new tested system microsatellite analysis can be done cheaper, faster, easier and with higher scientific accuracy. Sarel Halachmi, Michal Cohen, Raymond Szargel, and Nadin Cohen Copyright © 2007 Sarel Halachmi et al. All rights reserved. Infusion of Autologous Retrodifferentiated Stem Cells into Patients with Beta-Thalassemia Mon, 01 Jan 1900 00:00:00 +0000 Beta-thalassemia is a genetic, red blood cell disorder affecting the beta-globin chain of the adult hemoglobin gene. This results in excess accumulation of unpaired alpha-chain gene products leading to reduced red blood cell life span and the development of severe anemia. Current treatment of this disease involves regular blood transfusion and adjunct chelation therapy to lower blood transfusion–induced iron overload. Fetal hemoglobin switching agents have been proposed to treat genetic blood disorders, such as sickle cell anemia and beta-thalassemia, in an effort to compensate for the dysfunctional form of the beta-globin chain in adult hemoglobin. The rationale behind this approach is to pair the excess normal alpha-globin chain with the alternative fetal gamma-chain to promote red blood cell survival and ameliorate the anemia. Reprogramming of differentiation in intact, mature, adult white blood cells in response to inclusion of monoclonal antibody CR3/43 has been described. This form of retrograde development has been termed “retrodifferentiation”, with the ability to re-express a variety of stem cell markers in a heterogeneous population of white blood cells. This form of reprogramming, or reontogeny, to a more pluripotent stem cell state ought to recapitulate early hematopoiesis and facilitate expression of a fetal and/or adult program of hemoglobin synthesis or regeneration on infusion and subsequent redifferentiation. Herein, the outcome of infusion of autologous retrodifferentiated stem cells (RSC) into 21 patients with beta-thalassemia is described. Over 6 months, Infusion of 3-h autologous RSC subjected to hematopoietic-conducive conditions into patients with beta-thalassemia reduced mean blood transfusion requirement, increased mean fetal hemoglobin synthesis, and significantly lowered mean serum ferritin. This was always accompanied by an increase in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in such patients. No adverse side effects in response to the infusion of autologous RSC were noted.This novel clinical procedure may profoundly modify the devastating course of many genetic disorders in an autologous setting, thus paving the way to harnessing pluripotency from differentiated cells to regenerate transiently an otherwise genetically degenerate tissue such as thalassemic blood. Ilham Saleh Abuljadayel, Tasnim Ahsan, Huma Quereshi, Shakil Rizvi, Tamseela Ahmed, Sabiha Mirza Khan, Jawaid Akhtar, and Ghazi Dhoot Copyright © 2006 Ilham Saleh Abuljadayel et al. All rights reserved. Prune Belly Syndrome and Tracheo-esophageal Fistula in a Premature Neonate Mon, 01 Jan 1900 00:00:00 +0000 Lance Potter, Charles J. Rosser, S. Iskandar, and R. Lawrence Kroovand Copyright © 2004 Lance Potter et al. All rights reserved. The Role of the MRG Gene Family in Replicative Senescence and Immortalization Mon, 01 Jan 1900 00:00:00 +0000 James K. Leung, Patricia Pardo, and Olivia M. Pereira-Smith Copyright © 2001 James K. Leung et al. All rights reserved. Synergistic Effects of DNA and Cytoskeleton Damage-Inducing Agents on Apoptosis in Human Tumor Cell Lines Mon, 01 Jan 1900 00:00:00 +0000 Xueyuan Shang, Yasuko Fujita, Syuichi Oka, and Yoshimitsu Yamazaki Copyright © 2001 Xueyuan Shang et al. All rights reserved. Long Noncoding RNAs, Chromatin, and Development Mon, 01 Jan 1900 00:00:00 +0000 The way in which the genome of a multicellular organism can orchestrate the differentiation of trillions of cells and many organs, all from a single fertilized egg, is the subject of intense study. Different cell types can be defined by the networks of genes they express. This differential expression is regulated at the epigenetic level by chromatin modifications, such as DNA and histone methylation, which interact with structural and enzymatic proteins, resulting in the activation or silencing of any given gene. While detailed mechanisms are emerging on the role of different chromatin modifications and how these functions are effected at the molecular level, it is still unclear how their deposition across the epigenomic landscape is regulated in different cells. A raft of recent evidence is accumulating that implicates long noncoding RNAs (lncRNAs) in these processes. Most genomes studied to date undergo widespread transcription, the majority of which is not translated into proteins. In this review, we will describe recent work suggesting that lncRNAs are more than transcriptional "noise", but instead play a functional role by acting as tethers and guides to bind proteins responsible for modifying chromatin and mediating their deposition at specific genomic locations. We suggest that lncRNAs are at the heart of developmental regulation, determining the epigenetic status and transcriptional network in any given cell type, and that they provide a means to integrate external differentiation cues with dynamic nuclear responses through the regulation of a metastable epigenome. Better characterization of the lncRNA-protein "interactome" may eventually lead to a new molecular toolkit, allowing researchers and clinicians to modulate the genome at the epigenetic level to treat conditions such as cancer. Daniel P. Caley, Ryan C. Pink, Daniel Trujillano, and David R. F. Carter Copyright © 2010 Daniel P. Caley et al. All rights reserved. G1-CDK Activity Is Required for Both Proliferation and Viability of Myeloid/Erythroid Progenitors: A Critical Function of the v-Erba Oncoprotein Mon, 01 Jan 1900 00:00:00 +0000 Johannes Hofmann, Martina Sykora, and Hartmut Beug Copyright © 2001 Johannes Hofmann et al. All rights reserved. The Transcribed-Ultraconserved Regions: A Novel Class of Long Noncoding RNAs Involved in Cancer Susceptibility Mon, 01 Jan 1900 00:00:00 +0000 During recent years, novel approaches and new technologies have revealed a startling level of complexity of higher eukaryotes' transcriptome. A large proportion of the transcriptional output is represented by protein noncoding RNAs (ncRNAs) that arise from the “dark matter” of the genome. Focus on such sequences has revealed numerous RNA subtypes with several functions in RNA processing and gene expression regulation, and deep sequencing studies imply that many remain to be discovered. This review gives a picture of the state of the art of a novel class of long ncRNA known as transcribed-ultraconserved regions (T-UCRs). Most recent studies show that they are significantly altered in adult chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas, leading to the hypothesis that UCRs may play a role in tumorigenesis and promising innovative future T-UCR—based therapeutic approaches. Paola Scaruffi Copyright © 2011 Paola Scaruffi. All rights reserved. Genetic Mapping of Cell Survival Pathways using Enhanced Retroviral Mutagens Mon, 01 Jan 1900 00:00:00 +0000 Dan Liu, Xiaohong Yang, and Zhou Songyang Copyright © 2001 Dan Liu et al. All rights reserved. The Evolution of the Neural Basic Helix-Loop-Helix Proteins Mon, 01 Jan 1900 00:00:00 +0000 Basic Helix-Loop-Helix (bHLH) transcription factors control various aspects of the formation of the nervous system in the metazoans. In Drosophila some bHLH (such as the achaete-scuteatonal, and amos genes) act as proneural genes, directing ectodermal cells toward a neural fate. Their vertebrate orthologs, however, probably do not assume such a neural determination function, but rather control the decision made by neural precursors to generate neurons and not glial cells, as well as the progression of neuronal precursors toward differentiation into mature neurons. The proneural function of Drosophila bHLH genes may be an innovation that occurs in the evolutive lineage that leads to arthropods. In addition, although neural bHLH appear to be involved in the specification of neuronal identities, they probably do not confer by themselves neuronal type-specific properties to the cells. Rather, neural bHLH allow neural cells to correctly interpret specification and positional cues provided by other factors. Although bHLH genes are often expressed in complementary subsets of neural cells and/or expressed sequentially in those cells, the coding regions of the various neural bHLH appear largely interchangeable. We propose that the specific expression patterns have been acquired, following gene duplications, by subfunctional-ization, i.e., the partitioning of ancestral expression patterns among the duplicates and, by extension, we propose that subfunctionalization is a key process to understand the evolution of neural bHLH genes. Michel Vervoort and Valerie Ledent Copyright © 2001 Michel Vervoort and Valerie Ledent. All rights reserved. Inteins in Microbial Genomes: Distribution, Mechanism, and Function Mon, 01 Jan 1900 00:00:00 +0000 Inteins are self-splicing protein elements (134 to 608 amino acids). Over 125 inteins have been cataloged in InBase, the on-line intein database (, which includes the Intein Registry[1]. Inteins naturally present in pathogenic microbes represent novel, yet unexploited drug targets. Understanding the chemistry of the splicing reaction has allowed the manipulation of inteins, which are now used in many protein engineering applications[2]. Maurice W. Southworth and Francine B. Perler Copyright © 2002 Maurice W. Southworth and Francine B. Perler. All rights reserved. Attentional Phenotypes for the Analysis of Higher Mental Function Mon, 01 Jan 1900 00:00:00 +0000 We outline a strategy to relate normal cognitive processes to candidate genes. First, brain imaging is used to specify a cognitive process “attention” in terms of the neural networks involved. Next, evidence is presented showing that the operation of each network involves a dominant neuromodulator. Then we discuss development of a task designed to measure the efficiency of each network in normal individuals and consider evidence on the independence, reliability, and heritability of the networks. DNA from cheek swabs of subjects who performed the task are then used to examine candidate polymorphisms in genes related to the transmitters. We then examine the ability of these candidate alleles to predict the efficiency of relevant networks. This process has demonstrated that candidate genes are related to specific networks of attention to a greater degree than to overall performance as measured by reaction time and accuracy. These findings require replication and possible extension to other cognitive processes. John Fossella, Michael I. Posner, Jin Fan, James M. Swanson, and Donald W. Pfaff Copyright © 2002 John Fossella et al. All rights reserved. Role of Mitochondrial DNA in Aging Processes Mon, 01 Jan 1900 00:00:00 +0000 Giuseppe M. Attardi Copyright © 2001 Giuseppe M. Attardi. All rights reserved. Pattern of Organization of Human Mitochondrial Pseudogenes in the Nuclear Chromosomes Mon, 01 Jan 1900 00:00:00 +0000 Markus Woischnik and Carlos T. Moraes Copyright © 2002 Markus Woischnik and Carlos T. Moraes. All rights reserved. Comparing the Speed and Accuracy of the Smith and Waterman Algorithm as Implemented by Mpsrch with the Blast and Fasta Heuristics for Sequence Similarity Searching Mon, 01 Jan 1900 00:00:00 +0000 Michael A. Muratet Copyright © 2002 Michael A. Muratet. All rights reserved. A Special, Strict, Fat-Reduced, and Carbohydrate-Modified Diet Leads to Marked Weight Reduction even in Overweight Adolescents with Prader-Willi Syndrome (PWS) Mon, 01 Jan 1900 00:00:00 +0000 Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. Previously, we reported that our special diet for PWS patients is effective in the long run, if started early at about 2 years of age. Our objective in this study was to investigate if our special diet is also effective in PWS adolescents who are already overweight. We provided a strict, fat-reduced, and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five adolescents (two female, three male) with PWS. Patients were prospectively followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index were recorded over that period. The special diet was started at a mean age of 16 years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m2 (range: 32.4-55.5 kg/m2), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for-Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased to 33 kg/m2 (range: 26.7-38 kg/m2), as well as BMI-SDS +2.7 (range: 1.7-3.4 SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special diet was still effective in reducing weight after 4–6 years, with a mean BMI of 30.5 kg/m2 (range: 24.6–34.5 kg/m2) and a mean BMI-SDS of +2.1 (range: 0.7–2.9). We conclude that in a period of 2–6 years, our strict, fat-reduced, and carbohydrate-modified diet, with 10 kcal/cm height, is effective even in adolescents with PWS who are already overweight. Walter Bonfig, Kathi Dokoupil, and Heinrich Schmidt Copyright © 2009 Walter Bonfig et al. All rights reserved. Neurophysiological Endophenotypes, CNS Disinhibition, and Risk for Alcohol Dependence and Related Disorders Mon, 01 Jan 1900 00:00:00 +0000 Biological endophenotypes are more proximal to gene function than psychiatric diagnosis, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. The Collaborative Study on the Genetics of Alcoholism (COGA) has employed heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We found significant linkage and association between brain oscillations and genes involved with inhibitory neural networks (e.g., GABRA2, CHRM2), including frontal networks that are deficient in individuals with alcohol dependence, impulsivity, and related disinhibitory disorders. We reported significant linkage and linkage disequilibrium for the beta frequency of the EEG and GABRA2, a GABAA receptor gene on chromosome 4, which we found is also associated with diagnosis of alcohol dependence and related disorders. More recently, we found significant linkage and association with GABRA2 and interhemispheric theta coherence. We also reported significant linkage and linkage disequilibrium between the theta and delta event-related oscillations underlying P3 to target stimuli and GABRA2, a cholinergic muscarinic receptor gene on chromosome 7, which we found is also associated with diagnosis of alcohol dependence and related disorders. Thus, the identification of genes important for the expression of the endophenotypes (brain oscillations) helps when identifying genes that increase the susceptibility for risk of alcohol dependence and related disorders. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of complex disorders. We will present our recent genetic findings related to brain oscillations and Central Nervous System (CNS) disinhibition. Bernice Porjesz and Madhavi Rangaswamy Copyright © 2007 Bernice Porjesz and Madhavi Rangaswamy. All rights reserved. Platelets as Modifiers of Clinical Phenotype in Hemophilia Mon, 01 Jan 1900 00:00:00 +0000 Platelets occupy a central role in the maintenance of hemostasis by adhering to sites of vascular injury and facilitating thrombin generation, which leads to the formation of a fibrin clot. Patients with hemophilia exhibit defective thrombin generation secondary to reduced plasma factor concentrations, which can lead to excessive and sometimes life-threatening bleeding. Individuals differ greatly with respect to platelet function and platelets from different individuals differ inherently in their ability to enact thrombin generation, the key coagulative process that is deficient in hemophilia. Similarly, some patients with hemophilia seem to bleed less often than others despite exhibiting similar plasma factor levels. The biologic factors that underlie this phenotypic variability remain poorly understood, but evidence is reviewed supporting a role for platelets and platelet-related factors in modifying bleeding tendency in patients with hemophilia and potential directions for further clinical research in this area are discussed. Donald L. Yee Copyright © 2006 Donald L. Yee. All rights reserved. Characterize Protein Functional Relationships Based on Mrna Expression Profile Mon, 01 Jan 1900 00:00:00 +0000 Wei Ding, Luquan Wang, Ping Qiu, Jonathan Greene, and Marco Hernandez Copyright © 2002 Wei Ding et al. All rights reserved. Use of Antimuscarinics in the Elderly Mon, 01 Jan 1900 00:00:00 +0000 Overactive bladder (OAB) is a common, costly, and treatable condition in older persons. There is a wide array of available antimuscarinics for the treatment of these conditions; however, their side effect profile and the limited number of studies that evaluate their effect in the elderly curb their use. This review article focuses on OAB and its treatment, with special attention to the use of antimuscarinics in the elderly. Bhavin Patel, Tamara Bavendam, and Gopal Badlani Copyright © 2009 Bhavin Patel et al. All rights reserved. Crystal Structure of Murine Tcl1 Oncoprotein and Conserved Surface Features of the Molecules of the Tcl1 Family Mon, 01 Jan 1900 00:00:00 +0000 John M. Petock, Ivan Y. Torshin, Yuan-Fang Wang, Garrett C. Du Bois, Carlo M. Croce, Robert W. Harrison, and Robert T. Weber Copyright © 2002 John M. Petock et al. All rights reserved. Assistive Technology and Supplementary Treatment for Individuals with Rett Syndrome Mon, 01 Jan 1900 00:00:00 +0000 Rett syndrome (RS) is a neurological disorder, affecting mainly females, caused by MECP2 mutations usually resulting in severe physical disability. Due to the physical challenges faced by the individual with RS and her family, her rehabilitation program should support her throughout different daily activities, contexts, and surroundings. Rehabilitation interventions to reverse physical impairments include exercise of various types and different physical modalities. Nevertheless, in the vast majority of cases, hands-on therapeutic intervention opportunities are available for the client through a minute part of her waking hours. Hence, a supplementary system is required in order to engulf the child with a comprehensive network of support. Supplementary intervention can support physical impairment by introducing adaptive techniques, environmental modifications, and assistive technologies. The therapy program of an individual with RS should include the use of assistive technology when such devices improve the user's performance. The term “supplementary management” relates to the fact that this intervention may be performed by nonprofessionals with the supervision of a qualified therapist. Such an intervention can further support the therapeutic goals of the child, at a time when direct intervention is not supplied. The present article will review the available literature on the topic of assistive technology, incorporating the clinical knowledge of the author in the field of RS. Meir Lotan Copyright © 2007 Meir Lotan. All rights reserved. The Genetic Background Effect on Domesticated Species: A Mouse Evolutionary Perspective Mon, 01 Jan 1900 00:00:00 +0000 Laboratory mouse strains are known for their large phenotypic diversity and serve as a primary mammalian model in genotype-phenotype association studies. One possible attempt to understand the reason for this diversity could be addressed by careful investigation of the unique evolutionary history of their wild-derived founders and the consequence that it may have on the genetic makeup of the laboratory mouse strains during the history of human fancy breeding. This review will summarize recently published literature that endeavors to unravel the genetic background of laboratory mouse strains, as well as give new insights into novel evolutionary approaches. I will explain basic concepts of molecular evolution and the reason why it is important in order to infer function even among closely related wild and domesticated species. I will also discuss future frontiers in the field and how newly emerging sequencing technologies could help us to better understand the relationship between genotype and phenotype. Eli Reuveni Copyright © 2011 Eli Reuveni. All rights reserved. Caloric Intake, Oxidative Stress and Aging Mon, 01 Jan 1900 00:00:00 +0000 Cheol Koo Lee, Tomas A. Prolla, and Richard Weindruch Copyright © 2001 Cheol Koo Lee et al. All rights reserved. Some Deafness-Causing Mutations Can Be Silenced with the Appropriate Gene Partner Mon, 01 Jan 1900 00:00:00 +0000 Inheritance of a deafness-causing genotype does not necessarily mean that a person will have profound hearing loss. The presence of a modifying gene can change the effect of the deafness genotype. As an example, mutations found commonly among the deaf are at times found among their normal hearing relatives [1]. The implication is that there are genes or gene products whose interactions allow the normal physiological function of the inner ear despite a mutation that would normally disrupt the process. Deafness is not the first disorder in which modifiers can change the expected outcome, nor will it be the last, but it is very unusual for the outcome to be so dramatically changed. Edward Wilcox, Saima Riazuddin, and Sheikh Riazuddin Copyright © 2001 Edward Wilcox et al. All rights reserved. The CGRP-Antagonist BIBN4096BS Discriminates between the Action of α- and β-CGRP In Vitro Mon, 01 Jan 1900 00:00:00 +0000 Dongmei Wu, Kirsten Arnst, and Henry Doods Copyright © 2001 Dongmei Wu et al. All rights reserved. Genetic Models of Aerobic Endurance Running Capacity in Rats Mon, 01 Jan 1900 00:00:00 +0000 Steven L. Britton and Lauren Gerard Koch Copyright © 2002 Steven L. Britton and Lauren Gerard Koch. All rights reserved. Molecular Markers in Upper Urothelial Carcinoma Associated to Balkan Endemic Nephropathy. Aristolochic Acid as the Major Risk Factor of the Worldwide Disease Mon, 01 Jan 1900 00:00:00 +0000 The role of aristolochic acid in the etiology of Balkan endemic nephropathy (BEN) and associated upper urothelial carcinoma (UUC) was recently confirmed. The aim of this study was to determine the marker(s) specific for BEN-associated UUC. A total of 82 patients with UUC (38 from the BEN region and 44 control tumors) were included in the study. The Ki-67 index in BEN tumors correlated with the grade and multifocality (p < 0.05), but in regression analysis, only the grade of BEN tumor. The p53 index was significantly higher in BEN than in control tumors (p < 0.05), as well as the alteration of p53 (p < 0.05). BEN low-stage tumors, tumors without limphovascular invasion (LVI), and tumors of the renal pelvis had a higher p53 index than the control tumors (p < 0.05, 0.01, 0.05, respectively). The Ki-67 index was higher in control tumors with high-stage and solid growth than in BEN UUC (p < 0.050, 0.005). The Ki-67 correlated with the grade, growth, stage, LVI, and multifocality of UUC on the best way, but not with the group. In regression analysis, only multifocality of UUC had predictive influence on Ki-67 activity (p < 0.001). P53 correlated with the grade, growth, and group (p < 0.05). This investigation identifies the p53 pathway as the specific cell cycle marker involved in BEN-associated UUC. Ljubinka Jankovic Velickovic, Takanori Hattori, and Vladisav Stefanovic Copyright © 2009 Ljubinka Jankovic Velickovic et al. All rights reserved. Prediction of C Regulatory Elements Using Statistical Analysis Mon, 01 Jan 1900 00:00:00 +0000 Ping Qiu, Wei Ding, Ying Jiang, Jonathan Greene, and Luquan Wang Copyright © 2002 Ping Qiu et al. All rights reserved. The Extent of Lymphadenectomy at the Time of Radical Cystectomy for Bladder Cancer and its Impact on Prognosis and Survival Mon, 01 Jan 1900 00:00:00 +0000 Radical cystectomy has become a standard and effective treatment for muscle-invasive bladder cancer, however, the role and appropriate extent of a concomitant lymphadenectomy continues to evolve. We performed a detailed review of the English medical literature pertaining to the historical development and rationale for an extended lymphadenectomy in patients undergoing radical cystectomy. An historical perspective of lymphadenectomy and an anatomic account of bladder lymphatic drainage are presented. The boundaries and technique of an extended lymphadenectomy are also highlighted. Autopsy and contemporary survival data are presented to suggest that a more extensive lymphadenectomy has both prognostic and therapeutic utility. Furthermore, the stage of the primary bladder tumor, total number of lymph nodes removed, and the lymph node tumor burden are shown to be important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastasis. Radical cystectomy provides not only excellent local cancer control with low pelvic recurrence rates, but also the best long-term survival. Radical cystectomy with an appropriate extended lymphadenectomy, while surgically more challenging, does not significantly increase the morbidity or mortality of the procedure. Although the absolute limits of the lymph node dissection remain to be determined, there is an evolving body of data to support that an extended lymphadenectomy provides further diagnostic and therapeutic benefit. David Y. Josephson and John P. Stein Copyright © 2005 David Y. Josephson and John P. Stein. All rights reserved. Fmr1 KO Mice as a Possible Model of Autistic Features Mon, 01 Jan 1900 00:00:00 +0000 Autism is a pervasive developmental disorder appearing before the age of 3, where communication and social interactions are impaired. It also entails stereotypic behavior or restricted interests. Although this disorder was first described in 1943, little is still known about its etiology and that of related developmental disorders. Work with human patients has provided many data on neuropathological and cognitive symptoms, but our understanding of the functional defects at the cellular level and how they come about remains sketchy. To improve this situation, autism research is in need of valid animal models. However, despite a strong hereditary component, attempts to identify genes have generally failed, suggesting that many different genes are involved. As a high proportion of patients suffering from the Fragile X Syndrome show many autistic symptoms, a mouse model of this disorder could potentially also serve as a model for autism. The Fmr1 KO mouse is a valid model of the Fragile X Syndrome and many data on behavioral and sensory-motor characteristics of this model have been gathered. We present here an assessment of autistic features in this candidate model. We conclude that Fmr1 KO mice display several autistic-like features, but more work is needed to validate this model. Maude Bernardet and Wim E. Crusio Copyright © 2006 Maude Bernardet and Wim E. Crusio. All rights reserved. Genetic Correction of Sickle Cell Anemia and β-Thalassemia: Progress and New Perspective Mon, 01 Jan 1900 00:00:00 +0000 Gene therapy for β-globinopathies, particularly β-thalassemia and sickle cell anemia, holds promise for the future as a definitive corrective approach for these common and debilitating disorders. Correction of the β-globinopathies using lentivirus vectors carrying the β- or γ-globin genes and elements of the locus control region has now been well established in murine models, and an understanding of "what is required to cure these diseases" has been developed in the first decade of the 21st century. A clinical trial using one such vector has been initiated in France with intriguing results, while other trials are under development. Vector improvements to enhance the safety and efficiency of lentivirus vectors are being explored, while new strategies, including homologous recombination in induced pluripotent cells, for correction of sickle cell anemia have shown proof-of-concept in vitro. Here, a review is provided of the current substantial progress in genetic correction of β-globin disorders. Ajay Perumbeti and Punam Malik Copyright © 2010 Ajay Perumbeti and Punam Malik. All rights reserved. Longevity and Stem Cells: A Genetic Connection Mon, 01 Jan 1900 00:00:00 +0000 Hartmut Geiger, Jarrod M. True, Gerald de Haan, and Gary Van Zant Copyright © 2001 Hartmut Geiger et al. All rights reserved. Distribution of Receptor Activity Modifying Protein (RAMP) mRNAS in the Rat Central Nervous System Mon, 01 Jan 1900 00:00:00 +0000 K. R. Oliver, A. M. Kinsey, N. Keyvan-Fouladi, R. Heavens, and A. Wainwright Copyright © 2001 K.R. Oliver et al. All rights reserved. Role of microRNA Pathway in Mental Retardation Mon, 01 Jan 1900 00:00:00 +0000 Deficits in cognitive functions lead to mental retardation (MR). Understanding the genetic basis of inherited MR has provided insights into the pathogenesis of MR. Fragile X syndrome is one of the most common forms of inherited MR, caused by the loss of functional Fragile X Mental Retardation Protein (FMRP). Abrar Qurashi, Shuang Chang, and Peng Jin Copyright © 2007 Abrar Qurashi et al. All rights reserved. P-Body Components, microRNA Regulation, and Synaptic Plasticity Mon, 01 Jan 1900 00:00:00 +0000 What is the protein apparatus required for microRNA (miRNA) function and translational repression in neurons? This article reviews our recent work on Me31B, a conserved P-body protein present on Staufen-containing neuronal and maternal ribonucleoprotein (RNP) particles, which is required for dendrite morphogenesis and miRNA function in vivo. In addition, it provides new data to show that Me31B is present on and regulates formation of P-bodies in the Drosophila wing disc, where it has a general role in the regulation of miRNA function. While illuminating the function of this important RNA regulatory molecule, it also brings into focus a hypothesis of potentially broad significance. Namely, that P-body proteins may play important roles in regulation of dendrite-localized mRNAs and, thereby, in synaptic plasticity. A wide range of protein localization and early functional data support this hypothesis. We also discuss current knowledge of RNP particles that mediate translational repression and the implications of these findings for understanding translational control in neurons. Jens Hillebrand, Scott A. Barbee, and Mani Ramaswami Copyright © 2007 Jens Hillebrand et al. All rights reserved. Crystallographic Studies of Bacterial Exoribonucleases Mon, 01 Jan 1900 00:00:00 +0000 Tristan J. Fiedler and Arun Malhotra Copyright © 2002 Tristan J. Fiedler and Arun Malhotra. All rights reserved. Apoptosis Gene Hunting Using Retroviral Expression Cloning Mon, 01 Jan 1900 00:00:00 +0000 Claire L. Anderson and Gwyn T. Williams Copyright © 2001 Claire L. Anderson and Gwyn T. Williams. All rights reserved. Developmental Defects in Trisomy 21 and Mouse Models Mon, 01 Jan 1900 00:00:00 +0000 Aneuploidies have diverse phenotypic consequences, ranging from mental retardation and developmental abnormalities to susceptibility to common phenotypes and various neoplasms. This review focuses on the developmental defects of murine models of a prototype human aneuploidy: trisomy 21 (Down syndrome, DS, T21). Murine models are clearly the best tool for dissecting the phenotypic consequences of imbalances that affect single genes or chromosome segments. Embryos can be studied freely in mice, making murine models particularly useful for the characterization of developmental abnormalities. This review describes the main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models, and investigates phenotypes common to both species. Jean Maurice Delabar, Revital Aflalo-Rattenbac, and Nicole Créau Copyright © 2006 Jean Maurice Delabar et al. All rights reserved. Chemical Genetic Analysis of Protein Kinase Cascades Mon, 01 Jan 1900 00:00:00 +0000 Peter J. Alaimo, Michael A. Shogren-Knaak, and Kevan M. Shokat Copyright © 2002 Peter J. Alaimo et al. All rights reserved. Linear Methods for Analysis and Quality Control of Relative Expression Ratios from Quantitative Real-Time Polymerase Chain Reaction Experiments Mon, 01 Jan 1900 00:00:00 +0000 Relative expression quantitative real-time polymerase chain reaction (RT-qPCR) experiments are a common means of estimating transcript abundances across biological groups and experimental treatments. One of the most frequently used expression measures that results from such experiments is the relative expression ratio (RE), which describes expression in experimental samples (i.e., RNA isolated from organisms, tissues, and/or cells that were exposed to one or more experimental or nonbaseline condition) in terms of fold change relative to calibrator samples (i.e., RNA isolated from organisms, tissues, and/or cells that were exposed to a control or baseline condition). Over the past decade, several models of RE have been proposed, and it is now clear that endogenous reference gene stability and amplification efficiency must be assessed in order to ensure that estimates of RE are valid. In this review, we summarize key issues associated with estimating RE from cycle threshold data. In addition, we describe several methods based on linear modeling that enable researchers to estimate model parameters and conduct quality control procedures that assess whether model assumptions have been violated. Robert B. Page and Arnold J. Stromberg Copyright © 2011 Robert B. Page and Arnold J. Stromberg. All rights reserved. The Late Increase of Free Radicals During Genotoxic-Stress Induced Apoptosis is Associated with Cytochrome C Release From Mitochondria Induced by Caspase-Mediated Feedback Loop Amplification Mon, 01 Jan 1900 00:00:00 +0000 Quan Chen, Yucheng Chai, Suparna Mazuder, Judy Drazba, Guy Chisolm, and Alex Almasan Copyright © 2001 Quan Chen et al. All rights reserved. CDNA Cloning, Heterologous Expression and Characterization of Anti-Neuroexcitation Peptides (ANEPS) of Scorpion Buthus martensii Karsch Mon, 01 Jan 1900 00:00:00 +0000 Jing-Hai Zhang, Zi-Chun Hua, and De-Xu Zhu Copyright © 2001 Jing-Hai Zhang et al. All rights reserved. The Effect of Hoechst 33342 on Luciferase Gene Transcription and Translation Mon, 01 Jan 1900 00:00:00 +0000 Xinbo Zhang and Frederick L. Kiechle Copyright © 2001 Xinbo Zhang and Frederick L. Kiechle. All rights reserved. Induced Heme Oxygenase-1 Upregulation Protects Pancreatic Beta Cells from Apoptosis In Vitro Mon, 01 Jan 1900 00:00:00 +0000 Antonello Pileggi, Pierre Cattan, R. Damaris Molano, Thierry Berney, Caterina Vizzardelli, CHristopher Fraker, Robert Oliver, Camillo Ricordi, Ricardo Pastori, Fritz H. Bach, and Luca Inverardi Copyright © 2001 Antonello Pileggi et al. All rights reserved. Involvement of REL/NF-B Transcription Factors in Cellular Senescence Mon, 01 Jan 1900 00:00:00 +0000 David Bernard, Didier Monté, Bernard Vandenbunder, and Corinne Abbadie Copyright © 2001 David Bernard et al. All rights reserved. MicroRNAs in Vertebrate Synapse Development Mon, 01 Jan 1900 00:00:00 +0000 MicroRNAs are a relatively new class of small noncoding RNAs that play an important role in post-transcriptional gene regulation during development and disease. MicroRNAs are abundant in the vertebrate nervous system where they appear to function during neuronal fate determination and early differentiation. It is now becoming increasingly clear that microRNAs are also involved in later stages of neuronal development, namely, the formation and plasticity of synapses. Furthermore, first examples are emerging that microRNAs might contribute to the etiology of neuronal diseases characterized by synaptic dysfunction. This review will summarize the recent examples that describe a function of microRNAs in synapse formation, plasticity, and disease, and discuss future directions that promise to shed light on microRNA regulation by synaptic activity and microRNA function in higher cognitive functions, such as learning and memory. Roberto Fiore and Gerhard Schratt Copyright © 2007 Roberto Fiore and Gerhard Schratt. All rights reserved. Variable Clinical Phenotypes of α-Thalassemia Syndromes Mon, 01 Jan 1900 00:00:00 +0000 Genetic mutations of the α genes are common worldwide. In Asia and particularly Southeast Asia, they can result in clinically significant types of α-thalassemia, namely hemoglobin (Hb) H disease and Hb Bart's hydrops fetalis. The latter is generally a fatal intrauterine condition, while Hb H disease results in clinical complications that are frequently overlooked. The high prevalence of the carrier state and the burden of these diseases (and other α-thalassemia variants) call for more attention for improved screening methods and better care. Sylvia Titi Singer Copyright © 2009 Sylvia Titi Singer. All rights reserved. DNA-Related Pathways Defective in Human Premature Aging Mon, 01 Jan 1900 00:00:00 +0000 One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular pathology of these disorders. Vilhelm A. Bohr Copyright © 2002 Vilhelm A. Bohr. All rights reserved. Tumor-Suppressive microRNAs in Lung Cancer: Diagnostic and Therapeutic Opportunities Mon, 01 Jan 1900 00:00:00 +0000 Lorenzo F. Sempere, Xi Liu, and Ethan Dmitrovsky Copyright © 2009 Lorenzo F. Sempere et al. All rights reserved. RNA Editing in Hepatitis Delta Virus: Unsolved Puzzles Mon, 01 Jan 1900 00:00:00 +0000 RNA editing, or post-transcriptional changes in the sequences of RNAs, is being increasingly recognized as an important player in the regulation of gene expression in vertebrates and invertebrates. Different types of RNA editing have been reported. This review discuss the type of RNA editing caused by cellular enzymes known as adenosine deaminases that act on RNAs (ADARs), and it's significance in the lifecycle of an RNA virus, hepatitis delta virus. Geetha C. Jayan Copyright © 2004 Geetha C. Jayan. All rights reserved. Transgenic Killer Commensal Bacteria as Mucosal Protectants Mon, 01 Jan 1900 00:00:00 +0000 As first line of defense against the majority of infections and primary site for their transmission, mucosal surfaces of the oral cavity and genitourinary, gastrointestinal, and respiratory tracts represent the most suitable sites to deliver protective agents for the prevention of infectious diseases. Mucosal protection is important not only for life threatening diseases but also for opportunistic infections which currently represent a serious burden in terms of morbidity, mortality, and cost of cures. Candida albicans is among the most prevalent causes of mucosal infections not only in immuno- compromised patients, such as HIV-infected subjects who are frequently affected by oral and esophageal candidiasis, but also in otherwise healthy individuals, as in the case of acute vaginitis. Unfortunately, current strategies for mucosal protection against candidiasis are severely limited by the lack of effective vaccines and the relative paucity and toxicity of commercially available antifungal drugs. An additional option has been reported in a recent Luciano Polonelli Copyright © 2001 Luciano Polonelli. All rights reserved. Spatial Positioning of RET and H4 Following Radiation Exposure Leads to Tumor Development Mon, 01 Jan 1900 00:00:00 +0000 Exposure to ionizing radiation is a well-known risk factor for a number of human cancers, including leukemia, thyroid cancer, soft tissue sarcomas, and many others. Although it has been known for a long time that radiation exposure to the cell results in extensive DNA damage, including double strand DNA breaks, the exact mechanisms of radiation-induced carcinogenesis remain unknown. Recently, a large increase in incidence of thyroid cancer was observed in children exposed to radiation after the Chernobyl nuclear accident [1]. A high prevalence of chromosomal rearrangements involving the RET gene was found among these radiation-induced thyroid tumors [2,3]. As a result of such rearrangement, a portion of the RET gene is fused with another gene, typically with the H4 or ELE1. However, since the DNA targets of ionizing radiation are randomly distributed throughout the cell nucleus, the reason for predilection for the RET rearrangements in thyroid cells was unclear. Yuri E. Nikiforov Copyright © 2001 Yuri E. Nikiforov. All rights reserved. The TREX2 3′→ 5′ Exonuclease Physically Interacts with DNA Polymerase δ and Increases Its Accuracy Mon, 01 Jan 1900 00:00:00 +0000 Proofreading function by the 3′→ 5′ exonuclease of DNA polymerase δ (pol δ) is consistent with the observation that deficiency of the associated exonuclease can lead to a strong mutation phenotype, high error rates during DNA replication, and ultimately cancer. We have isolated pol δd from isotonic (pol δi) and detergent (pol δd) calf thymus extracts. Pol δd had a 20-fold higher ratio of exonuclease to DNA polymerase than pol δi. This was due to the physical association of the TREX2 exonuclease to pol δd, which was missing from pol δi. Pol δd was fivefold more accurate than pol δi under error-prone conditions (1 μM dGTP and 20 dATP, dCTP, and dTTP) in a M13mp2 DNA forward mutation assay, and fourfold more accurate in an M13mp2T90 reversion assay. Under error-free conditions (20 μM each of the four dNTPs), however, both polymerases showed equal fidelity. Our data suggested that autonomous 3′→ 5′ exonucleases, such as TREX2, through its association with pol I can guarantee high fidelity under difficult conditions in the cell (e.g., imbalance of dNTPs) and can add to the accuracy of the DNA replication machinery, thus preventing mutagenesis. Igor V. Shevelev, Kristijan Ramadan, and Ulrich Hubscher Copyright © 2002 Igor V. Shevelev et al. All rights reserved.