New Journal of Science The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Melanins: Skin Pigments and Much More—Types, Structural Models, Biological Functions, and Formation Routes Tue, 18 Mar 2014 07:36:42 +0000 This review presents a general view of all types of melanin in all types of organisms. Melanin is frequently considered just an animal cutaneous pigment and is treated separately from similar fungal or bacterial pigments. Similarities concerning the phenol precursors and common patterns in the formation routes are discussed. All melanins are formed in a first enzymatically-controlled phase, generally a phenolase, and a second phase characterized by an uncontrolled polymerization of the oxidized intermediates. In that second phase, quinones derived from phenol oxidation play a crucial role. Concerning functions, all melanins show a common feature, a protective role, but they are not merely photoprotective pigments against UV sunlight. In pathogenic microorganisms, melanization becomes a virulence factor since melanin protects microbial cells from defense mechanisms in the infected host. In turn, some melanins are formed in tissues where sunlight radiation is not a potential threat. Then, their redox, metal chelating, or free radical scavenging properties are more important than light absorption capacity. These pigments sometimes behave as a double-edged sword, and inhibition of melanogenesis is desirable in different cells. Melanin biochemistry is an active field of research from dermatological, biomedical, cosmetical, and microbiological points of view, as well as fruit technology. F. Solano Copyright © 2014 F. Solano. All rights reserved. Advances and Prospects in Cancer Immunotherapy Thu, 13 Mar 2014 09:59:25 +0000 Cancer immunotherapy is a promising and effective treatment modality for patients with cancers. Cytokine, anticytokine, and antibody therapies appear to be effective in treating various forms of cancer. The human papillomavirus vaccine is protective for cervical cancer, and this discovery has paved the way to the development of cancer vaccines for other forms of virus-associated cancers such as liver cancer and Merkel cell carcinoma. Clinical trials have demonstrated that adoptive cell therapy using tumor-infiltrating lymphocytes can induce tumor regression in approximately 75% of metastatic melanoma patients, suggesting the possibility of using similar technique to effectively treat breast, lung, and renal cancers in the near future. Besides, genetically engineered T cells transduced with genes encoding specific T cell receptors and chimeric antigen receptors have been shown effective in the treatment of cancer patients. These studies suggest that combination therapies are superior choices in cancer immunotherapy for patients. Juhua Zhou Copyright © 2014 Juhua Zhou. All rights reserved. Programmed Cell Death in Neurospora crassa Sun, 02 Mar 2014 13:59:28 +0000 Programmed cell death has been studied for decades in mammalian cells, but simpler organisms, including prokaryotes, plants, and fungi, also undergo regulated forms of cell death. We highlight the usefulness of the filamentous fungus Neurospora crassa as a model organism for the study of programmed cell death. In N. crassa, cell death can be triggered genetically due to hyphal fusion between individuals with different allelic specificities at het loci, in a process called “heterokaryon incompatibility.” Chemical induction of cell death can also be achieved upon exposure to death-inducing agents like staurosporine, phytosphingosine, or hydrogen peroxide. A summary of the recent advances made by our and other groups on the discovery of the mechanisms and mediators underlying the process of cell death in N. crassa is presented. A. Pedro Gonçalves and Arnaldo Videira Copyright © 2014 A. Pedro Gonçalves and Arnaldo Videira. All rights reserved. Mammalian MYC Proteins and Cancer Sun, 02 Feb 2014 13:50:41 +0000 The MYC family of proteins is a group of basic-helix-loop-helix-leucine zipper transcription factors that feature prominently in cancer. Overexpression of MYC is observed in the vast majority of human malignancies and promotes an extraordinary set of changes that impact cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion, differentiation, and metastasis. The purpose of this review is to introduce the reader to the mammalian family of MYC proteins, highlight important functional properties that endow them with their potent oncogenic potential, describe their mechanisms of action and of deregulation in cancer cells, and discuss efforts to target the unique properties of MYC, and of MYC-driven tumors, to treat cancer. William P. Tansey Copyright © 2014 William P. Tansey. All rights reserved. Between Amyloids and Aggregation Lies a Connection with Strength and Adhesion Sun, 02 Feb 2014 00:00:00 +0000 We tell of a journey that led to discovery of amyloids formed by yeast cell adhesins and their importance in biofilms and host immunity. We begin with the identification of the adhesin functional amyloid-forming sequences that mediate fiber formation in vitro. Atomic force microscopy and confocal microscopy show 2-dimensional amyloid “nanodomains” on the surface of cells that are activated for adhesion. These nanodomains are arrays of adhesin molecules that bind multivalent ligands with high avidity. Nanodomains form when adhesin molecules are stretched in the AFM or under laminar flow. Treatment with anti-amyloid perturbants or mutation of the amyloid sequence prevents adhesion nanodomain formation and activation. We are now discovering biological consequences. Adhesin nanodomains promote formation and maintenance of biofilms, which are microbial communities. Also, in abscesses within candidiasis patients, we find adhesin amyloids on the surface of the fungi. In both human infection and a Caenorhabditis elegans infection model, the presence of fungal surface amyloids elicits anti-inflammatory responses. Thus, this is a story of how fungal adhesins respond to extension forces through formation of cell surface amyloid nanodomains, with key consequences for biofilm formation and host responses. Peter N. Lipke, Caleen Ramsook, Melissa C. Garcia-Sherman, Desmond N. Jackson, Cho X. J. Chan, Michael Bois, and Stephen A. Klotz Copyright © 2014 Peter N. Lipke et al. All rights reserved. Biology of the KCNQ1 Potassium Channel Wed, 29 Jan 2014 08:34:05 +0000 Ion channels are essential for basic cellular function and for processes including sensory perception and intercellular communication in multicellular organisms. Voltage-gated potassium (Kv) channels facilitate dynamic cellular repolarization during an action potential, opening in response to membrane depolarization to facilitate K+ efflux. In both excitable and nonexcitable cells other, constitutively active, K+ channels provide a relatively constant repolarizing force to control membrane potential, ion homeostasis, and secretory processes. Of the forty known human Kv channel pore-forming α subunits that coassemble in various combinations to form the fundamental tetrameric channel pore and voltage sensor module, KCNQ1 is unique. KCNQ1 stands alone in having the capacity to form either channels that are voltage-dependent and require membrane depolarization for activation, or constitutively active channels. In mammals, KCNQ1 regulates processes including gastric acid secretion, thyroid hormone biosynthesis, salt and glucose homeostasis, and cell volume and in some species is required for rhythmic beating of the heart. In this review, the author discusses the unique functional properties, regulation, cell biology, diverse physiological roles, and involvement in human disease states of this chameleonic K+ channel. Geoffrey W. Abbott Copyright © 2014 Geoffrey W. Abbott. All rights reserved. Vacuolar H+-ATPase: An Essential Multitasking Enzyme in Physiology and Pathophysiology Thu, 23 Jan 2014 14:16:42 +0000 Vacuolar H+-ATPases (V-ATPases) are large multisubunit proton pumps that are required for housekeeping acidification of membrane-bound compartments in eukaryotic cells. Mammalian V-ATPases are composed of 13 different subunits. Their housekeeping functions include acidifying endosomes, lysosomes, phagosomes, compartments for uncoupling receptors and ligands, autophagosomes, and elements of the Golgi apparatus. Specialized cells, including osteoclasts, intercalated cells in the kidney and pancreatic beta cells, contain both the housekeeping V-ATPases and an additional subset of V-ATPases, which plays a cell type specific role. The specialized V-ATPases are typically marked by the inclusion of cell type specific isoforms of one or more of the subunits. Three human diseases caused by mutations of isoforms of subunits have been identified. Cancer cells utilize V-ATPases in unusual ways; characterization of V-ATPases may lead to new therapeutic modalities for the treatment of cancer. Two accessory proteins to the V-ATPase have been identified that regulate the proton pump. One is the (pro)renin receptor and data is emerging that indicates that V-ATPase may be intimately linked to renin/angiotensin signaling both systemically and locally. In summary, V-ATPases play vital housekeeping roles in eukaryotic cells. Specialized versions of the pump are required by specific organ systems and are involved in diseases. L. Shannon Holliday Copyright © 2014 L. Shannon Holliday. All rights reserved. Tumour Immunogenicity, Antigen Presentation, and Immunological Barriers in Cancer Immunotherapy Sun, 05 Jan 2014 09:04:37 +0000 Since the beginning of the 20th century, scientists have tried to stimulate the antitumour activities of the immune system to fight against cancer. However, the scientific effort devoted on the development of cancer immunotherapy has not been translated into the expected clinical success. On the contrary, classical antineoplastic treatments such as surgery, radiotherapy, and chemotherapy are the first line of treatment. Nevertheless, there is compelling evidence on the immunogenicity of cancer cells and the capacity of the immune system to expand cancer-specific effector cytotoxic T cells. However, the effective activation of anticancer T cell responses strongly depends on efficient tumour antigen presentation from professional antigen presenting cells such as dendritic cells (DCs). Several strategies have been used to boost DC antigen presenting functions, but at the end cancer immunotherapy is not as effective as would be expected according to preclinical models. In this review, we comment on these discrepancies, focusing our attention on the contribution of regulatory T cells and myeloid-derived suppressor cells to the lack of therapeutic success of DC-based cancer immunotherapy. David Escors Copyright © 2014 David Escors. All rights reserved.