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Several Novel (several + novel)

Distribution by Scientific Domains
Medical Sciences60%

Terms modified by Several Novel

  • several novel gene
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    Selected Abstracts

    Novel domains of the prokaryotic two-component signal transduction systems

    FEMS MICROBIOLOGY LETTERS, Issue 1 2001
    Michael Y. Galperin
    Abstract The archetypal two-component signal transduction systems include a sensor histidine kinase and a response regulator, which consists of a receiver CheY-like domain and a DNA-binding domain. Sequence analysis of the sensor kinases and response regulators encoded in complete bacterial and archaeal genomes revealed complex domain architectures for many of them and allowed the identification of several novel conserved domains, such as PAS, GAF, HAMP, GGDEF, EAL, and HD-GYP. All of these domains are widely represented in bacteria, including 19 copies of the GGDEF domain and 17 copies of the EAL domain encoded in the Escherichia coli genome. In contrast, these novel signaling domains are much less abundant in bacterial parasites and in archaea, with none at all found in some archaeal species. This skewed phyletic distribution suggests that the newly discovered complexity of signal transduction systems emerged early in the evolution of bacteria, with subsequent massive loss in parasites and some horizontal dissemination among archaea. Only a few proteins containing these domains have been studied experimentally, and their exact biochemical functions remain obscure; they may include transformations of novel signal molecules, such as the recently identified cyclic diguanylate. Recent experimental data provide the first direct evidence of the participation of these domains in signal transduction pathways, including regulation of virulence genes and extracellular enzyme production in the human pathogens Bordetella pertussis and Borrelia burgdorferi and the plant pathogen Xanthomonas campestris. Gene-neighborhood analysis of these new domains suggests their participation in a variety of processes, from mercury and phage resistance to maintenance of virulence plasmids. It appears that the real picture of the complexity of phosphorelay signal transduction in prokaryotes is only beginning to unfold. [source]

    Sorafenib: Where do we go from here?,

    HEPATOLOGY, Issue 1 2010
    Abby B. Siegel
    The approval of sorafenib as the first effective drug for the treatment of hepatocellular carcinoma (HCC) represents a milestone in the treatment of this disease. A better understanding of HCC pathogenesis has led to the development of several novel targeted treatments. HCC is treated in a uniquely multidisciplinary way requiring surgeons, hepatologists, interventional radiologists, and oncologists. This review describes the molecular pathogenesis of HCC, explores current and future treatments based on these pathways, and describes how these new therapies may augment existing approaches to HCC treatment.(HHEPATOLOGY 2010;) [source]

    Coupling of mesh-free methods with finite elements: basic concepts and test results

    INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 10 2006
    T. Rabczuk
    Abstract This paper reviews several novel and older methods for coupling mesh-free particle methods, particularly the element-free Galerkin (EFG) method and the smooth particle hydrodynamics (SPH), with finite elements (FEs). We study master,slave couplings where particles are fixed across the FE boundary, coupling via interface shape functions such that consistency conditions are satisfied, bridging domain coupling, compatibility coupling with Lagrange multipliers and hybrid coupling methods where forces from the particles are applied via their shape functions on the FE nodes and vice versa. The hybrid coupling methods are well suited for large deformations and adaptivity and the coupling procedure is independent of the particle distance and nodal arrangement. We will study the methods for several static and dynamic applications, compare the results to analytical and experimental data and show advantages and drawbacks of the methods. Copyright © 2006 John Wiley & Sons, Ltd. [source]

    Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays

    THE PROSTATE, Issue 3 2004
    Aruna V. Krishnan
    Abstract BACKGROUND 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] exerts growth inhibitory, pro-differentiating, and pro-apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH)2D3 -regulated gene expression in the LNCaP human prostate cancer cells. METHODS mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH)2D3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real-time PCR assays. RESULTS 1,25(OH)2D3 most substantially increased the expression of the insulin-like growth factor binding protein-3 (IGFBP-3) gene. Our analysis also revealed several novel 1,25(OH)2D3 -responsive genes. Interestingly, some of the key genes regulated by 1,25(OH)2D3 are also androgen-responsive genes. 1,25(OH)2D3 also down-regulated genes that mediate androgen catabolism. CONCLUSIONS The putative 1,25(OH)2D3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell,cell and cell,matrix interactions, DNA repair, and inhibition of metastasis. The up-regulation of IGFBP-3 gene has been shown to be crucial in 1,25(OH)2D3 -mediated inhibition of LNCaP cell growth. 1,25(OH)2D3 regulation of androgen-responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH)2D3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti-cancer effects of 1,25(OH)2D3 may lead to better approaches to the prevention and treatment of prostate cancer. © 2004 Wiley-Liss, Inc. [source]

    Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology

    BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2010
    Adam L. VanWert
    Abstract Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender. Copyright © 2009 John Wiley & Sons, Ltd. [source]