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Molecular Regulation (molecular + regulation)
Selected AbstractsMolecular regulation of postsynaptic differentiation at the neuromuscular junctionIUBMB LIFE, Issue 11 2005Raghavan Madhavan Abstract The neuromuscular junction (NMJ) is a synapse that develops between a motor neuron and a muscle fiber. A defining feature of NMJ development in vertebrates is the re-distribution of muscle acetylcholine (ACh) receptors (AChRs) following innervation, which generates high-density AChR clusters at the postsynaptic membrane and disperses aneural AChR clusters formed in muscle before innervation. This process in vivo requires MuSK, a muscle-specific receptor tyrosine kinase that triggers AChR re-distribution when activated; rapsyn, a muscle protein that binds and clusters AChRs; agrin, a nerve-secreted heparan-sulfate proteoglycan that activates MuSK; and ACh, a neurotransmitter that stimulates muscle and also disperses aneural AChR clusters. Moreover, in cultured muscle cells, several additional muscle- and nerve-derived molecules induce, mediate or participate in AChR clustering and dispersal. In this review we discuss how regulation of AChR re-distribution by multiple factors ensures aggregation of AChRs exclusively at NMJs. IUBMB Life, 57: 719-730, 2005 [source] Molecular regulation of androgen action in prostate cancer,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Scott M. Dehm Abstract Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This review will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. We will also summarize several recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer. J. Cell. Biochem. 99: 333,344, 2006. © 2006 Wiley-Liss, Inc. [source] Molecular regulation of cognitive functions and developmental plasticity: impact of GABAA receptorsJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Hanns Möhler Abstract By controlling spike timing and sculpting neuronal rhythms, inhibitory interneurons play a key role in regulating neuronal circuits and behavior. The pronounced diversity of GABAergic (,-aminobutyric acid) interneurons is paralleled by an extensive diversity of GABAA receptor subtypes. The region- and domain-specific location of these receptor subtypes offers the opportunity to gain functional insights into the role of defined neuronal circuits. These developments are reviewed with regard to the regulation of sleep, anxiety, memory, sensorimotor processing and post-natal developmental plasticity. [source] Molecular regulation of the developing commissural plateTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 18 2010Randal X. Moldrich Abstract The commissural plate of the developing mouse brain showing all telencephalic midline commissures in single plane of tissue. The Journal of Comparative Neurology, Volume 518, Number 18, 3645,3661. [source] Molecular regulation of the developing commissural plateTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 18 2010Randal X. Moldrich Abstract Coordinated transfer of information between the brain hemispheres is essential for function and occurs via three axonal commissures in the telencephalon: the corpus callosum (CC), hippocampal commissure (HC), and anterior commissure (AC). Commissural malformations occur in over 50 human congenital syndromes causing mild to severe cognitive impairment. Disruption of multiple commissures in some syndromes suggests that common mechanisms may underpin their development. Diffusion tensor magnetic resonance imaging revealed that forebrain commissures crossed the midline in a highly specific manner within an oblique plane of tissue, referred to as the commissural plate. This specific anatomical positioning suggests that correct patterning of the commissural plate may influence forebrain commissure formation. No analysis of the molecular specification of the commissural plate has been performed in any species; therefore, we utilized specific transcription factor markers to delineate the commissural plate and identify its various subdomains. We found that the mouse commissural plate consists of four domains and tested the hypothesis that disruption of these domains might affect commissure formation. Disruption of the dorsal domains occurred in strains with commissural defects such as Emx2 and Nfia knockout mice but commissural plate patterning was normal in other acallosal strains such as Satb2,/,. Finally, we demonstrate an essential role for the morphogen Fgf8 in establishing the commissural plate at later developmental stages. The results demonstrate that correct patterning of the commissural plate is an important mechanism in forebrain commissure formation. J. Comp. Neurol. 518:3645,3661, 2010. © 2010 Wiley-Liss, Inc. [source] The alcohol dehydrogenases of Saccharomyces cerevisiae: a comprehensive reviewFEMS YEAST RESEARCH, Issue 7 2008Olga De Smidt Abstract Alcohol dehydrogenases (ADHs) constitute a large family of enzymes responsible for the reversible oxidation of alcohols to aldehydes with the concomitant reduction of NAD+ or NADP+. These enzymes have been identified not only in yeasts, but also in several other eukaryotes and even prokaryotes. The ADHs of Saccharomyces cerevisiae have been studied intensively for over half a century. With the ever-evolving techniques available for scientific analysis and since the completion of the Yeast Genome Project, a vast amount of new information has been generated during the past 10 years. This review attempts to provide a brief summary of the wealth of knowledge gained from earlier studies as well as more recent work. Relevant aspects regarding the primary and secondary structure, kinetic characteristics, function and molecular regulation of the ADHs in S. cerevisiae are discussed in detail. A brief outlook also contemplates possible future research opportunities. [source] Changes in chromatin structure and methylation of the human interleukin-1, gene during monopoiesisIMMUNOLOGY, Issue 3 2010Inga Wessels Summary Interleukin-1, (IL-1,) induces the expression of a variety of proteins responsible for acute inflammation and chronic inflammatory diseases. However, the molecular regulation of IL-1, expression in myeloid differentiation has not been elucidated. In this study the chromatin structure of the IL-1, promoter and the impact of methylation on IL-1, expression in monocytic development were examined. The results revealed that the IL-1, promoter was inaccessible in undifferentiated promyeloid HL-60 cells but highly accessible in differentiated monocytic cells which additionally acquired the ability to produce IL-1,. Accessibilities of differentiated cells were comparable to those of primary monocytes. Lipopolysaccharide (LPS) stimulation did not affect promoter accessibility in promyeloid and monocytic HL-60 cells, demonstrating that the chromatin remodelling of the IL-1, promoter depends on differentiation and not on the transcriptional status of the cell. Demethylation via 5-aza-2,-deoxycytodine led to the induction of IL-1, expression in undifferentiated and differentiated cells, which could be increased after LPS stimulation. Our data indicate that the IL-1, promoter is reorganized into an open poised conformation during monopoiesis being a privilege of mature monocytes but not of the entire myeloid lineage. As a second mechanism, IL-1, expression is regulated by methylation acting independently of the developmental stage of myeloid cells. [source] Tumor metastasis and the lymphatic vasculatureINTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Jonathan P. Sleeman Abstract Tumor-associated lymphatic vessels act as a conduit by which disseminating tumor cells access regional lymph nodes and form metastases there. Lymph node metastasis is of major prognostic significance for many types of cancer, although lymph node metastases are themselves rarely life-threatening. These observations focus our attention on understanding how tumor cells interact with the lymphatic vasculature, and why this interaction is so significant for prognosis. Tumors interact with the lymphatic vasculature in a number of ways, including vessel co-option, chemotactic migration and invasion into lymphatic vessels and induction of lymphangiogenesis. Tumor-induced lymphangiogenesis both locally and in regional lymph nodes has been correlatively and functionally associated with metastasis formation and poor prognosis. The investigation of the molecular regulation of lymphangiogenesis has identified ways of interfering with prolymphangiogenic signaling. Blockade of tumor-induced lymphangiogenesis in preclinical models inhibits metastasis formation in lymph nodes and often also in other organs, suggesting that blocking the lymphatic route of dissemination might suppress metastasis formation not only in lymph nodes but also in other organs. However, randomized clinical trials that have investigated the efficacy of therapeutic removal of lymph nodes have concluded that lymph node metastases act only as indicators that primary tumors have developed metastatic potential, and do not govern the further spread of metastatic cells. To reconcile these apparently paradoxical observations we suggest a model in which tumor-induced lymphangiogenesis and lymph node metastasis formation act as indicators that tumors are producing factors that can act systemically to promote metastasis formation in distant organs. © 2009 UICC [source] Co-ordination of osmotic stress responses through osmosensing and signal transduction events in fishesJOURNAL OF FISH BIOLOGY, Issue 8 2010T. G. Evans This review centres upon the molecular regulation of osmotic stress responses in fishes, focusing on how osmosensing and signal transduction events co-ordinate changes in the activity and abundance of effector proteins during osmotic stress and how these events integrate into osmotic stress responses of varying magnitude. The concluding sections discuss the relevance of osmosensory signal transduction to the evolution of euryhalinity and present experimental approaches that may best stimulate future research. Iterating the importance of osmosensing and signal transduction during fish osmoregulation may be pertinent amidst the increased use of genomic technologies that typically focus solely on changes in the abundances of gene products, and may limit insight into critical upstream events that occur mainly through post-translational mechanisms. [source] Terpenoid Indole Alkaloids Biosynthesis and Metabolic Engineering in Catharanthus roseusJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 7 2007Dong-Hui Liu Abstract Catharanthus roseus L. (Madagascar periwinkle) biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids (vinblastine and vincristine) and antihypertensive alkaloids (ajmalicine and serpentine). The multi-step terpenoid indole alkaloids (TIAs) biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed. [source] New light on the biology and developmental potential of haematopoietic stem cells and progenitor cellsJOURNAL OF INTERNAL MEDICINE, Issue 4 2009M. Sigvardsson Abstract. Even though stem cells have been identified in several tissues, one of the best understood somatic stem cells is the bone marrow residing haematopoietic stem cell (HSC). These cells are able to generate all types of blood cells found in the periphery over the lifetime of an animal, making them one of the most profound examples of tissue-restricted stem cells. HSC therapy also represents one of the absolutely most successful cell-based therapies applied both in the treatment of haematological disorders and cancer. However, to fully explore the clinical potential of HSCs we need to understand the molecular regulation of cell maturation and lineage commitment. The extensive research effort invested in this area has resulted in a rapid development of the understanding of the relationship between different blood cell lineages and increased understanding for how a balanced composition of blood cells can be generated. In this review, several of the basic features of HSCs, as well as their multipotent and lineage-restricted offspring, are addressed, providing a current view of the haematopoietic development tree. Some of the basic mechanisms believed to be involved in lineage restriction events including activities of permissive and instructive external signals are also discussed, besides transcription factor networks and epigenetic alterations to provide an up-to-date view of early haematopoiesis. [source] Anti-inflammatory effect of retinoic acid on prostaglandin synthesis in cultured cortical astrocytesJOURNAL OF NEUROCHEMISTRY, Issue 1 2008Eric Kampmann Abstract Prostanoids are important mediators of inflammation and pain signaling. Although it is now well accepted that astrocytes participate in inflammatory reactions in the CNS, the molecular regulation of this activity is still largely unknown. Specifically, the regulation of prostanoid synthesis by this type of glia remains to be resolved. Recent evidence suggests that the transcriptional regulator retinoic acid (RA) is involved in regulation of the immune response. We have investigated the expression pattern of the enzymes that catalyze prostanoid and leukotriene synthesis in cultured cortical astrocytes, their stimulation by lipopolysaccharides (LPS) and their regulation by RA. The data indicate that astrocytes are an important source of prostaglandins (PGs) and that RA reduces their inflammatory biosynthesis. LPS treatment induced the expression of enzymes for the production of arachidonic acid and PGs but caused down-regulation of a PG degrading enzyme and of leukotriene synthesizing enzymes that compete with PG synthesis. Consequently, the secretion of the PGE2 was highly increased after LPS exposure. RA counteracted the inflammatory regulation of cyclooxygenase (COX)-2 mRNA and protein in astrocytes and thereby reduced the synthesis of PGE2 by approximately 60%. In the absence of LPS, RA enhanced the expression of COX-1 mRNA. In conclusion, RA might be effective in suppressing inflammatory processes in the brain by inhibiting PG synthesis. [source] Leukotriene pathway genetics and pharmacogenetics in allergyALLERGY, Issue 6 2009N. P. Duroudier Leukotrienes (LT) are biologically active lipid mediators known to be involved in allergic inflammation. Leukotrienes have been shown to mediate diverse features of allergic conditions including inflammatory cell chemotaxis/activation and smooth muscle contraction. Cysteinyl leukotrienes (LTC4, LTD4 and, LTE4) and the dihydroxy leukotriene LTB4 are generated by a series of enzymes/proteins constituting the LT synthetic pathway or 5-lipoxygenase (5-LO) pathway. Their function is mediated by interacting with multiple receptors. Leukotriene receptor antagonists (LTRA) and LT synthesis inhibitors (LTSI) have shown clinical efficacy in asthma and more recently in allergic rhinitis. Despite growing knowledge of leukotriene biology, the molecular regulation of these inflammatory mediators remains to be fully understood. Genes encoding enzymes of the 5-LO pathway (i.e. ALOX5, LTC4S and LTA4H) and encoding for LT receptors (CYSLTR1/2 and LTB4R1/2) provide excellent candidates for disease susceptibility and severity; however, their role remains unclear. Preliminary data also suggest that 5-LO pathway/receptor gene polymorphism can predict patient responses to LTSI and LTRA; however, the exact mechanisms require elucidation. The aim of this review was to summarize the recent advances in the knowledge of these important mediators, focusing on genetic and pharmacogenetic aspects in the context of allergic phenotypes. [source] Neuroendocrine regulation of puberty in fish: Insights from the grey mullet (Mugil cephalus) modelMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2008Josephine N. Nocillado Abstract We investigated the molecular regulation of pubertal development in the grey mullet, Mugil cephalus, a relatively late-maturing teleost fish. We have isolated and characterized the cDNAs of key reproductive genes along the brain,pituitary,gonadal (BPG) axis as well as the promoters of genes that modulate the axis at multiple levels. Together with relevant findings from other model species, we propose a conceptual model of the neuroendocrine regulation of puberty in the female grey mullet. Research areas that warrant further investigation are identified in the model. Mol. Reprod. Dev. 75: 355,361, 2008. © 2007 Wiley-Liss, Inc. [source] The morphogenesis of lobed plant cells in the mesophyll and epidermis: organization and distinct roles of cortical microtubules and actin filamentsNEW PHYTOLOGIST, Issue 3 2005Emmanuel Panteris Summary The morphogenesis of lobed plant cells has been considered to be controlled by microtubule (MT) and/or actin filament (AF) organization. In this article, a comprehensive mechanism is proposed, in which distinct roles are played by these cytoskeletal components. First, cortical MT bundles and, in the case of pavement cells, radial MT arrays combined with MT bundles determine the deposition of local cell wall thickenings, the cellulose microfibrils of which copy the orientation of underlying MTs. Cell growth is thus locally prevented and, consequently, lobes and constrictions are formed. Arch-like tangential expansion is locally imposed at the external periclinal wall of pavement cells by the radial arrangement of cellulose microfibrils at every wall thickening. Whenever further elongation of the original cell lobes occurs, AF patches assemble at the tips of growing lobes. Intercellular space formation is promoted or prevented by the opposite or alternate, respectively, arrangement of cortical MT arrays between neighboring cells. The genes that are possibly involved in the molecular regulation of the above morphogenetic procedure by MT and AF array organization are reviewed. [source] Stem cells in pathobiology and regenerative medicine,THE JOURNAL OF PATHOLOGY, Issue 2 2009MR Alison Abstract This issue of the Journal of Pathology contains 16 articles largely dealing with the role of tissue-specific adult stem cells in the pathogenesis of disease, notably cancer. These authoritative reviews begin by describing the current knowledge regarding the identity and molecular regulation of normal tissue-specific stem cells, before itemizing their role in the aetiology and progression of disease. Fundamental concepts regarding the stem cell niche have been gleaned from studies of germ line stem cells in Drosophila and Caenorhabditis elegans, and these are described in detail in this issue. Somatic cell reprogramming, a process underlying not only therapeutic cloning but also the production of induced pluripotent stem (iPS) cells, is further discussed. Much attention is given to embryonic stem (ES) and iPS cells within the scientific community; this issue of the Journal of Pathology redresses this imbalance by illustrating the pivotal role of adult stem cells in much of human disease. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] T cell adhesion mechanisms revealed by receptor lateral mobility,BIOPOLYMERS, Issue 5 2008Christopher W. Cairo Cell surface receptors mediate the exchange of information between cells and their environment. In the case of adhesion receptors, the spatial distribution and molecular associations of the receptors are critical to their function. Therefore, understanding the mechanisms regulating the distribution and binding associations of these molecules is necessary to understand their functional regulation. Experiments characterizing the lateral mobility of adhesion receptors have revealed a set of common mechanisms that control receptor function and thus cellular behavior. The T cell provides one of the most dynamic examples of cellular adhesion. An individual T cell makes innumerable intercellular contacts with antigen presenting cells, the vascular endothelium, and many other cell types. We review here the mechanisms that regulate T cell adhesion receptor lateral mobility as a window into the molecular regulation of these systems, and we present a general framework for understanding the principles and mechanisms that are likely to be common among these and other cellular adhesion systems. We suggest that receptor lateral mobility is regulated via four major mechanisms,reorganization, recruitment, dispersion, and anchoring,and we review specific examples of T cell adhesion receptor systems that utilize one or more of these mechanisms. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 409,419, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] An Hg2+ -Gated Chiral Molecular Switch Created by Using Binaphthalene Molecules with Two Anthracene Units and Two 1,3-Dithiole-2-thione (1,3-Dithiole-2-one) UnitsCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2008Cheng Wang Abstract By integrating the features of anthracene, 1,3-dithiole-2-thione, and binaphthalene units, (S)- 1 and its analogue (S)- 2, which contains two 1,3-dithiole-2-one units instead of 1,3-dithiole-2-thione, were studied for creating a new molecular regulation system and building a gated chiral molecular switch. The results show that the photodimerization is controlled by the remote functional-group transformation of CS into CO, thus providing an elegant example of molecular regulation. The photodimerization of two anthracene units induces circular dichroism (CD) spectral variation. Overall, the CD spectrum can be remotely modulated by Hg2+ in (S)- 1, which leads to an Hg2+ -gated chiral molecular switch. [source] Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulationCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2009Z. Ma Summary Plasminogen activator inhibitor (PAI)-1 is a major inhibitor of the fibrinolytic system. PAI-1 levels are markedly increased in asthmatic airways, and mast cells (MCs), a pivotal cell type in the pathogenesis of asthma, are one of the main sources of PAI-1 production. Recent studies suggest that PAI-1 may promote the development of asthma by regulating airway remodelling, airway hyperresponsiveness (AHR), and allergic inflammation. The single guanosine nucleotide deletion/insertion polymorphism (4G/5G) at ,675 bp of the PAI-1 gene is the major genetic determinant of PAI-1 expression. Plasma PAI-1 level is higher in people with the 4G/4G genotype than in those with the 5G/5G genotype. A strong association between the 4G/5G polymorphism and the risk and the severity of asthma has been suggested. Levels of plasma IgE and PAI-1 and severity of AHR are greater in asthmatic patients with the 4G/4G genotype than in those with the 5G/5G genotype. The PAI-1 promoter with the 4G allele renders higher transcription activity than the PAI-1 promoter with the 5G allele in stimulated MCs. The molecular mechanism for the 4G allele-mediated higher PAI-1 expression is associated with greater binding of upstream stimulatory factor-1 to the E-box adjacent to the 4G site (E-4G) than to the E-5G. In summary, PAI-1 may play an important role in the pathogenesis of asthma. Further studies evaluating the mechanisms of PAI-1 action and regulation may lead to the development of a novel prognostic factor and therapeutic target for the treatment and prevention of asthma and other PAI-1-associated diseases. [source] | ||||||||||||||||||||||||||||