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Selected AbstractsA MAS NMR Study of the Bacterial ABC Transporter ArtMPCHEMBIOCHEM, Issue 4 2010Vivien Lange Dr. Abstract ATP-binding cassette (ABC) transport systems facilitate the translocation of substances, like amino acids, across cell membranes energised by ATP hydrolysis. This work describes first structural studies on the ABC transporter ArtMP from Geobacillus stearothermophilus in native lipid environment by magic-angle spinning NMR spectroscopy. The 2D crystals of ArtMP and 3D crystals of isolated ArtP were prepared in different nucleotide-bound or -unbound states. From selectively 13C,15N-labelled ArtP, several sequence-specific assignments were obtained, most of which could be transferred to spectra of ArtMP. Residues Tyr133 and Pro134 protrude directly into the ATP-binding pocket at the interface of the ArtP subunits, and hence, are sensitive monitors for structural changes during nucleotide binding and hydrolysis. Distinct sets of NMR shifts were obtained for ArtP with different phosphorylation states of the ligand. Indications were found for an asymmetric or inhomogeneous state of the ArtP dimer bound with triphosphorylated nucleotides. With this investigation, a model system was established for screening all functional states occurring in one ABC transporter in native lipid environment. [source] An actualistic perspective into Archean worlds , (cyano-)bacterially induced sedimentary structures in the siliciclastic Nhlazatse Section, 2.9 Ga Pongola Supergroup, South AfricaGEOBIOLOGY, Issue 1 2008N. NOFFKE ABSTRACT Extensive microbial mats colonize sandy tidal flats that form along the coasts of today's Earth. The microbenthos (mainly cyanobacteria) respond to the prevailing physical sediment dynamics by biostabilization, baffling and trapping, as well as binding. This biotic,physical interaction gives rise to characteristic microbially induced sedimentary structures (MISS) that differ greatly from both purely physical structures and from stromatolites. Actualistic studies of the MISS on modern tidal flats have been shown to be the key for understanding equivalent fossil structures that occur in tidal and shelf sandstones of all Earth ages. However, until now the fossil record of Archean MISS has been poor, and relatively few specimens have been found. This paper describes a study location that displays a unique assemblage with a multitude of exceptionally preserved MISS in the 2.9-Ga-old Pongola Supergroup, South Africa. The ,Nhlazatse Section' includes structures such as ,erosional remnants and pockets', ,multidirected ripple marks', ,polygonal oscillation cracks', and ,gas domes'. Optical and geochemical analyses support the biogenicity of microscopic textures such as filamentous laminae or ,orientated grains'. Textures resembling filaments are lined by iron oxide and hydroxides, as well as clay minerals. They contain organic matter, whose isotope composition is consistent with carbon of biological origin. The ancient tidal flats of the Nhlazatse Section record four microbial mat facies that occur in modern tidal settings as well. We distinguish endobenthic and epibenthic microbial mats, including planar, tufted, and spongy subtypes. Each microbial mat facies is characterized by a distinct set of MISS, and relates to a typical tidal zone. The microbial mat structures are preserved in situ, and are consistent with similar features constructed today by benthic cyanobacteria. However, other mat-constructing microorganisms also could have formed the structures in the Archean tidal flats. [source] How is geriatrics different from general internal medicine?GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2004Thomas E Finucane Geriatrics and general internal medicine overlap greatly: most sick patients seen by a generalist are elderly and geriatricians care for nearly the full spectrum of diseases seen in internal medicine. Differences between the two disciplines can be seen in the areas of patient care, research and administration. As a group, geriatric patients are different from young adults because they are more likely to have multiple chronic illnesses, to depend on others, to be frail and to die in the near future. Each of these characteristics requires special knowledge on the part of the physician. The research agenda in geriatrics extends from attempts to find the molecular basis of sarcopenia and frailty to clinical research on the support of caregivers, who are themselves critically important to patients. In the US, nursing homes are required to have medical directors; this position is largely administrative and requires a distinct set of knowledge and attitudes. Clinical care, research and administrative efforts must all respond to the enormous number of patients who will develop cognitive impairment over the next three decades. Because the number of elderly patients so far exceeds the ability of geriatricians to provide care, education and ,geriatricizing' other specialties will also be an important mission for geriatricians. Proper reimbursement presents a serious challenge to physicians who care for the frail elderly. If geriatricians take care of the frailest, sickest and most vulnerable patients, but reimbursement mechanisms cannot recognize this fact, then all geriatricians will soon go bankrupt. [source] The T-cell receptor repertoire of regulatory T cellsIMMUNOLOGY, Issue 4 2008Rafal Pacholczyk Summary The CD4+ CD25+ regulatory population of T cells (Treg cells), which expresses the forkhead family transcription factor (Foxp3), is the key component of the peripheral tolerance mechanism that protects us from a variety of autoimmune diseases. Experimental evidence shows that Treg cells recognize a wide range of antigenic specificities with increased reactivity to self antigens, although the affinity of these interactions remains to be further defined. The Treg repertoire is highly diverse with a distinct set of T-cell receptors (TCRs), and yet is overlapping to some extent with the repertoire of conventional T cells (Tconv cells). The majority of Treg cells are generated in the thymus. However, the role of the TCR specificity in directing thymic precursors to become Treg or Tconv cells remains unclear. On the one hand, the higher self reactivity of Treg cells and utilization of different TCRs in Treg and Tconv repertoires suggest that in TCR interactions an initial decision is made about the ,suitability' of a developing thymocyte to become a Treg cell. On the other hand, as Treg cells can recognize a wide range of foreign antigens, have a diverse TCR repertoire, and show some degree of overlap with Tconv cells, the signals through the TCR may be complementary to the TCR-independent process that generates precursors of Treg cells. In this review, we discuss how different features of the Treg repertoire influence our understanding of Treg specificities and the role of self reactivity in the generation of this population. [source] QPSK differential space time coding on different unitary matrices sets and initializationsINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 9 2006Jia Hou Abstract This paper investigates a distinct set of complex unitary matrices for differential space time coding by using QPSK modulation. The numerical results show that the proper selection of the initial transmission matrix and the set of unitary matrices can efficiently improve the bit error rate performance, especially for the antennas correlated fading channel. The computer simulations are evaluated over slow and fast Rayleigh fading channels. Copyright © 2005 John Wiley & Sons, Ltd. [source] Globalization: An Ascendant Paradigm?INTERNATIONAL STUDIES PERSPECTIVES, Issue 1 2002James H. Mittelman International Studies is on the cusp of a debate between para-keepers, observers who are steadfast about maintaining the prevailing paradigms and deny that globalization offers a fresh way of thinking about the world, and para-makers, who bring into question what they regard as outmoded categories and claim to have shifted to an innovatory paradigm. This distinction is a heuristic that allows for various gradations and dynamic interactions between the keepers and the makers. It helps to identify anomalies in and discomfort with International Studies. Partly as a response to these problems, globalization studies has evolved and may be tentatively delimited by a distinct set of characteristics. But, in the near term, there is no looming Kuhnian crisis in the sense of an impending overthrow that would quickly sweep away reigning paradigms. Given that systematic research on globalization is only slightly more than a decade in the making, it is most likely that International Studies has entered an interregnum between the old and the new. At this time, as a paradigm, globalization is more of a potential than a worked-out framework. It may be best understood as a proto-paradigm. [source] Genetic and Environmental Determinants of Peak Bone Mass in Young Men and WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2002Fiona E. A. Mcguigan Ph.D. Abstract Peak bone mass is an important risk factor for the development of osteoporosis in later life. Previous work has suggested that genetic, intrauterine, and environmental factors all contribute to the regulation of bone mass, but the ways in which they interact with each other to do so remain poorly understood. In this study, we investigated the relationship between peak bone mass and polymorphisms of the vitamin D receptor (VDR), estrogen receptor (ER) ,, and collagen type I,1 (COLIA1) genes in relation to other factors such as birth weight, lifestyle diet, and exercise in a population-based cohort of 216 women and 244 men in their early 20s. Stepwise multiple regression analysis showed that body weight was the strongest predictor of bone mineral density (BMD) in women, accounting for 16.4% of the variance in spine BMD and 8.4% of the variance in femoral neck BMD. Other significant predictors were VDR genotype (3.8%) and carbohydrate intake (1.6%) at the spine and vitamin D intake (3.4%) and ER genotype (3.4%) at the femoral neck. Physical activity was the strongest predictor of BMD in men, accounting for 6.7% of the variance at the spine and 5.1% at the hip. Other significant predictors were body weight (5%) and ER PvuII genotype (2.8%) at the spine and weight (3.4%) and alcohol intake (2%) at the femoral neck. Birth weight was not a significant predictor of BMD at either site but COLIA1 genotype significantly predicted birth weight in women, accounting for 4.3% of the variance. We conclude that peak bone mass is regulated by an overlapping but distinct set of environmental and genetic influences that differ in men and women. However, much of the variance in BMD was unexplained by the variables studied here, which suggests that either most of the genes that regulate BMD remain to be discovered or major environmental influences on BMD exist that have not yet been identified. [source] Efficient optimization strategies with constraint programming,AICHE JOURNAL, Issue 2 2010Prakash R. Kotecha Abstract In this article, we propose novel strategies for the efficient determination of multiple solutions for a single objective, as well as globally optimal pareto fronts for multiobjective, optimization problems using Constraint Programming (CP). In particular, we propose strategies to determine, (i) all the multiple (globally) optimal solutions of a single objective optimization problem, (ii) K -best feasible solutions of a single objective optimization problem, and (iii) globally optimal pareto fronts (including nonconvex pareto fronts) along with their multiple realizations for multiobjective optimization problems. It is shown here that the proposed strategy for determining K -best feasible solutions can be tuned as per the requirement of the user to determine either K -best distinct or nondistinct solutions. Similarly, the strategy for determining globally optimal pareto fronts can also be modified as per the requirement of the user to determine either only the distinct set of pareto points or determine the pareto points along with all their multiple realizations. All the proposed techniques involve appropriately modifying the search techniques and are shown to be computationally efficient in terms of not requiring successive re-solving of the problem to obtain the required solutions. This work therefore convincingly addresses the issue of efficiently determining globally optimal pareto fronts; in addition, it also guarantees the determination of all the possible realizations associated with each pareto point. The uncovering of such solutions can greatly aid the designer in making informed decisions. The proposed approaches are demonstrated via two case studies, which are nonlinear, combinatorial optimization problems, taken from the area of sensor network design. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Hepatitis A virus (HAV) proteinase 3C inhibits HAV IRES-dependent translation and cleaves the polypyrimidine tract-binding proteinJOURNAL OF VIRAL HEPATITIS, Issue 9 2010T. Kanda Summary., Hepatitis A virus (HAV) infection is still an important issue worldwide. A distinct set of viruses encode proteins that enhance viral cap-independent translation initiation driven by an internal ribosome entry site (IRES) and suppress cap-dependent host translation. Unlike cytolytic picornaviruses, replication of HAV does not cause host cell shut off, and it has been questioned whether HAV proteins interfere with its own and/or host translation. HAV proteins were coexpressed in Huh-7 cells with reporter genes whose translation was initiated by either cap-dependent or cap-independent mechanisms. Among the proteins tested, HAV proteinase 3C suppressed viral IRES-dependent translation. Furthermore, 3C cleaved the polypyrimidine tract-binding protein (PTB) whose interaction with the HAV IRES had been demonstrated previously. The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication. [source] Lawyers of the Right: Networks and OrganizationLAW & SOCIAL INQUIRY, Issue 4 2007Anthony Paik Lawyers for conservative and libertarian causes are active in organizing and mobilizing interest groups within the conservative coalition, and networks of relationships among those lawyers help to maintain and shape the coalition. Using data gathered in interviews with seventy-two such lawyers, this article analyzes characteristics of the lawyers and the structure of their networks. The findings suggest that the networks are divided into segments or blocks that are identified with particular constituencies, but that a distinct set of actors with extensive relationships serves to bridge the constituencies. Measures of centrality and brokerage confirm the structural importance of these actors in the network, and a search of references in news media confirms their prominence or prestige. This "core" set of actors occupies the "structural hole" in the network that separates the business constituency from religious conservatives. Libertarians, located near the core of the network, also occupy an intermediate position. Regression analysis of ties within the network suggests that the Federalist Society plays an important role in bringing the lawyers together. [source] Specific and pleiotropic patterns of mRNA regulation by ArcZ, a conserved, Hfq-dependent small RNAMOLECULAR MICROBIOLOGY, Issue 1 2009Kai Papenfort Summary The small RNA, ArcZ (previously RyhA/SraH), was discovered in several genome-wide screens in Escherichia coli and Salmonella. Its high degree of genomic conservation, its frequent recovery by shotgun sequencing, and its association with the RNA chaperone, Hfq, identified ArcZ as an abundant enterobacterial ,core' small RNA, yet its function remained unknown. Here, we report that ArcZ acts as a post-transcriptional regulator in Salmonella, repressing the mRNAs of the widely distributed sdaCB (serine uptake) and tpx (oxidative stress) genes, and of STM3216, a horizontally acquired methyl-accepting chemotaxis protein (MCP). Both sdaCB and STM3216 are regulated by sequestration of the ribosome binding site. In contrast, the tpx mRNA is targeted in the coding sequence (CDS), arguing that CDS targeting is more common than appreciated. Transcriptomic analysis of an arcZ deletion strain further argued for the existence of a distinct set of Salmonella loci specifically regulated by ArcZ. In contrast, increased expression of the sRNA altered the steady-state levels of > 16% (> 750) of all Salmonella mRNAs, and rendered the bacteria non-motile. Deep sequencing detected a dramatically changed profile of Hfq-bound sRNAs and mRNAs, suggesting that the unprecedented pleiotropic effects by a single sRNA might in part be caused by altered post-transcriptional regulation. [source] Insights into the membrane proteome of rat liver peroxisomes: Microsomal glutathione-S-transferase is shared by both subcellular compartmentsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2006Markus Islinger Dr. Abstract Peroxisomes are ubiquitous "multipurpose" organelles of eukaryotic cells. Their matrix enzymes catalyze mainly catabolic and anabolic reactions of lipid metabolism, thus contributing to the regulation of lipid homeostasis. Since most metabolites must be actively transported across the peroxisomal membrane and since individual proteins and protein complexes play functional roles in such transport processes, we analyzed the peroxisomal membrane proteome. Benzyldimethyl- n -hexadecylammoniumchloride (16-BAC)/SDS-2-D-PAGE and mass spectrometry were used to characterize the proteomes of highly purified "light" and "heavy" peroxisomes of rat liver obtained by density gradient centrifugation. In both populations, the major integral membrane proteins could be detected in high concentrations, verifying 16-BAC/SDS-2-D-PAGE as a suitable tool for the preparation of membrane proteomes destined for mass spectrometric analysis. Both reliable and reproducible detection of a distinct set of microsomal (ER) membrane proteins, including microsomal glutathione-S-transferase (mGST), in light and heavy peroxisomal fractions was also possible. Compared with the abundance of most microsomal membrane proteins, we found mGST to be specifically enriched in peroxisomal membrane fractions. Furthermore, C terminus epitope-tagged mGST versions were localized at least in part to peroxisomes in different mammalian cell lines. Taken together, these data suggest that the peroxisomal GST is not a mere ER-contaminant, but a bona fide protein comprising the membrane proteome of both intracellular compartments. In addition, we could detect several mitochondrial proteins in light peroxisome fractions. This finding may likely indicate a physical association of light peroxisomes with mitochondria, since the organelles could be partly separated by mechanical stress. Whether this association is of functional importance awaits further investigation. [source] Case for and against specificity of depression in Alzheimer's diseasePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2010Christian Even MD Aims:, The aims of this study were to assess the epidemiological, phenomenological, and pathophysiological evidence that suggests the specificity of depression associated with Alzheimer's disease (AD). Methods:, We reviewed the English-language literature. Results:, Depression occurs significantly more often in patients with AD than in the general elderly population. While development of depression in response to the disability and emotional stress of AD may be a contributory factor in some patients, several studies showed that depression was not, or was only seldom, related to self-awareness of AD and these studies could not explain the high prevalence figures. To overcome the overlapping phenomenology of the two diseases, specific diagnostic criteria have been developed for depression in this context. Mixed findings have come from neuropathological and neuroimaging studies, with some evidence linking the underlying neural substrate of AD and depression, suggesting an overlapping cause of primary depression and depression comorbid with AD. Few randomized controlled trials for depression associated with AD have been conducted, with rather poor results for the use of antidepressants. Conclusions:, Currently, depression associated with AD is not considered a separate disorder by regulatory authorities and is unlikely to be considered as such in the near future. Several obstacles remain to support such a specific position, including the heterogenous nature of depression in general and within AD itself, the lack of a distinct set of symptoms, and limited treatment. [source] Molecular Correlates of Scarring in Kidney Transplants: The Emergence of Mast Cell TranscriptsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009M. Mengel In the Banff consensus, infiltrates in areas of scarring are ignored. This study aimed to characterize the molecular correlates and clinical significance of scarring and inflammation in scarred areas. We assessed the extent of interstitial infiltrates, tubulitis and scarring in 129 clinically indicated renal allograft biopsies, and correlated the results with microarray expression data and allograft survival. Findings were validated in 50 additional biopsies. Transplants with scarring had a worse prognosis if the scarred area showed infiltrates. Infiltration in unscarred and scarred areas was associated with reduced death censored graft survival. In microarray analysis, infiltration in unscarred areas strongly (>r ± 0.4) correlated with 484 transcripts associated with cytotoxic T cells, interferon-gamma, macrophages and injury. Scarring correlated with a distinct set of 172 transcripts associated with B cells, plasma cells, and others of unknown significance. The strongest correlation was with four mast cell transcripts. In biopsies with scarring, high expression of mast cell transcripts was associated with reduced graft survival and poor functional recovery. In renal allograft biopsies, infiltrates in scarred areas have implications for poor outcomes. Scarring is associated with a distinct pattern of inflammatory molecules, including B cell/immunoglobulin but particularly mast cell-associated transcripts, which correlated with poor outcomes. [source] Response of vegetation and vertebrate fauna to 23 years of fire exclusion in a tropical Eucalyptus open forest.AUSTRAL ECOLOGY, Issue 2 2004Australia, Northern Territory Abstract This opportunistic study compares the vegetation, fuel loads and vertebrate fauna of part of a 120-ha block of tropical open forest protected from fire for 23 years, and an adjacent block burnt annually over this period. Total fuel loads did not differ significantly between the unburnt and annually burnt sites, but their composition was markedly different, with far less grassy fuel, but far more litter fuel, in the unburnt block. There were major differences between treatments in the composition of trees and shrubs, manifest particularly in the number of stems. There was no overall difference in plant species richness between the two treatments, but richness of woody species was far higher in the unburnt treatment, and of annual and perennial grasses, and perennial herbs in the annually burnt treatment. Change in plant species composition from annually burnt to unburnt treatment was directional, in that there was a far higher representation of rainforest-associated species (with the percentage of woody stems attributable to ,rainforest' species increasing from 24% of all species in the annually burnt treatment to 43% in the unburnt treatment, that of basal area from 9% to 30%, that of species richness from 8% to 17%, and that of cover from 12 to 47%). The vertebrate species composition varied significantly between treatments, but there was relatively little difference in species richness (other than for a slightly richer reptile fauna in the unburnt treatment). Again, there was a tendency for species that were more common in the unburnt treatment to be rainforest-associated species. The results from this study suggest that there is a sizeable and distinct set of species that are associated with relatively long-unburnt environments, and hence that are strongly disadvantaged under contemporary fire regimes. We suggest that such species need to be better accommodated by fire management through strategic reductions in the frequency of burning. [source] Spontaneous mutation in mice provides new insight into the genetic mechanisms that pattern the seminal vesicles and prostate glandDEVELOPMENTAL DYNAMICS, Issue 4 2003Paul C. Marker Abstract The seminal vesicles and prostate gland are anatomically adjacent male sex-accessory glands. Although they arise from different embryonic precursor structures and express distinct sets of secretory proteins, these organs share common features in their developmental biology. A key shared developmental feature is the elaboration of complex secretory epithelia with tremendous surface area from simple precursor structures with juxtaposed epithelial and mesenchymal cells. In this study, new insight into the nature of the biological processes that underlie glandular morphogenesis is achieved by analyzing the phenotypes present in mice that harbor a spontaneous mutation, seminal vesicle shape (svs), previously identified for causing altered seminal vesicle morphology in adults. An examination of seminal vesicle development in svs mice provides the first evidence that the concurrent processes of epithelial branching and epithelial infolding are distinct processes under separate genetic control. It also provides the first direct evidence that the thickness and topology of the smooth muscle layer in the seminal vesicles are determined by interaction with the glandular epithelium during the branching process. In addition, the seminal vesicle phenotype in svs mice is shown to phenocopy the morphologic form present in certain other mammals such as the guinea pig, raising the possibility that the svs mutation is the sort of variant that arises during evolution. By also including an investigation of the prostate gland, this study also identifies previously unrecognized phenotypes in svs prostates, including increased gland size and dramatically reduced levels of branching morphogenesis. Finally, this study advances the goal of identifying the svs gene by mapping the svs mutation relative to known molecular markers and testing Fgfr2 as a candidate gene. The finding that the svs mutation maps to a genomic region syntenic to a region frequently deleted in human prostate tumors, together with the prostatic phenotype present in svs mice, further raises the interesting possibility that the svs mutation will identify a candidate prostate tumor suppressor gene. Developmental Dynamics 226:643,653, 2003. © 2003 Wiley-Liss, Inc. [source] Strategies for DNA interstrand crosslink repair: Insights from worms, flies, frogs, and slime moldsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010Mitch McVey Abstract DNA interstrand crosslinks (ICLs) are complex lesions that covalently link both strands of the DNA double helix and impede essential cellular processes such as DNA replication and transcription. Recent studies suggest that multiple repair pathways are involved in their removal. Elegant genetic analysis has demonstrated that at least three distinct sets of pathways cooperate in the repair and/or bypass of ICLs in budding yeast. Although the mechanisms of ICL repair in mammals appear similar to those in yeast, important differences have been documented. In addition, mammalian crosslink repair requires other repair factors, such as the Fanconi anemia proteins, whose functions are poorly understood. Because many of these proteins are conserved in simpler metazoans, nonmammalian models have become attractive systems for studying the function(s) of key crosslink repair factors. This review discusses the contributions that various model organisms have made to the field of ICL repair. Specifically, it highlights how studies performed with C. elegans, Drosophila, Xenopus, and the social amoeba Dictyostelium serve to complement those from bacteria, yeast, and mammals. Together, these investigations have revealed that although the underlying themes of ICL repair are largely conserved, the complement of DNA repair proteins utilized and the ways in which each of the proteins is used can vary substantially between different organisms. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source] Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy) exert different patterns of pollution and toxicity to sea urchin embryosENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2002Giovanni Pagano Abstract This study was designed to investigate the composition and toxicity of solid residues from bauxite manufacturing plants. Soil and dust samples were collected in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy). Samples were analyzed for their content of some selected inorganic contaminants by means of inductively coupled plasma optical emission spectroscopy (ICP-OES) either following acid digestion procedures or by seawater release of soluble components. Toxicity was tested by sea urchin bioassays to evaluate a set of toxicity endpoints including acute embryotoxicity, developmental defects, changes in sperm fertilization success, transmissible damage from sperm to the offspring, and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe, Mn, Pb, Ti, and Zn; sample composition (seawater-soluble cotaminants) and toxicity showed a noteworthy association. The most severe toxicity to embryogenesis and to sperm fertilization success was exerted by some Portovesme samples (0.03,0.5% w/v), with a significant association between toxicity and dose-related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust sample (G20) from the Gardanne factory showed increasing seawater release of Al, Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea urchin embryos and sperm (offspring quality). Soil samples around the Gardanne factory showed the highest frequency of toxic soil sites eastward from the factory. The present data point to solid deposition from bauxite plants as a potential subject of environmental health concern. The results suggest that extraction methods for evaluating the toxicity of complex mixtures should be based on the environmental availability of mixture components. The differences in sample toxicity among the tested sites, however, suggest possible site-to-site variability in geochemical and/or technological parameters. [source] Enhanced B-cell activation mediated by TLR4 and BCR crosstalk,EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2008Susana Minguet Abstract Despite the important role of B lymphocytes as a bridge between the innate and the adaptive immune system, little is known regarding lipopolysaccharide (LPS) recognition, activation of signalling networks or conceivable cooperation between LPS and the B-cell antigen receptor (BCR). Here, we show that primary B cells can efficiently discriminate between different LPS chemotypes, responding with at least 100-fold higher sensitivity to rough-form LPS compared with smooth-form LPS. Using genetically modified mice, we demonstrate that B lymphocytes recognize all LPS chemotypes via Toll-like receptor 4 (TLR4). In addition, we dissect the signalling pathways that lead to CD69 upregulation upon TLR4 and BCR activation in primary B cells. Our data suggest that TLR4 and BCR induce CD69 transcription via two distinct sets of signalling molecules, exerting quantitative and qualitative differences in B-cell activation. Finally, we show that simultaneous stimulation of TLR4 and BCR additively elevates B-cell activation. In contrast, co-engagement of TLR4 and BCR by antigen-coupled LPS synergistically enhances activation of B cells, pointing out attractive targets for signalling crosstalk in B lymphocytes. [source] CONVERGENCE AND THE MULTIDIMENSIONAL NICHEEVOLUTION, Issue 2 2005Luke J. Harmon Abstract Convergent evolution has played an important role in the development of the ecological niche concept. We investigated patterns of convergent and divergent evolution of Caribbean Anolis lizards. These lizards diversified independently on each of the islands of the Greater Antilles, producing the same set of habitat specialists on each island. Using a phylogenetic comparative framework, we examined patterns of morphological convergence in five functionally distinct sets of morphological characters: body size, body shape, head shape, lamella number, and sexual size dimorphism. We find evidence for convergence among members of the habitat specialist types for each of these five datasets. Furthermore, the patterns of convergence differ among at least four of the five datasets; habitat specialists that are similar for one set of characters are often greatly different for another. This suggests that the habitat specialist niches into which these anoles have evolved are multidimensional, involving several distinct and independent aspects of morphology. [source] Transcriptional activity of interferon regulatory factor (IRF)-3 depends on multiple protein,protein interactionsFEBS JOURNAL, Issue 24 2002Hongmei Yang Virus infection results in the activation of a set of cellular genes involved in host antiviral defense. IRF-3 has been identified as a critical transcription factor in this process. The activation mechanism of IRF-3 is not fully elucidated, yet it involves a conformational change triggered by the virus-dependent phosphorylation of its C-terminus. This conformational change leads to nuclear accumulation, DNA binding and transcriptional transactivation. Here we show that two distinct sets of Ser/Thr residues of IRF-3, on phosphorylation, synergize functionally to achieve maximal activation. Remarkably, we find that activated IRF-3 lacks transcriptional activity, but activates transcription entirely through the recruitment of the p300/CBP coactivators. Moreover, we show that two separate domains of IRF-3 interact with several distinct regions of p300/CBP. Interference with any of these interactions leads to a complete loss of transcriptional activity, suggesting that a bivalent interaction is essential for coactivator recruitment by IRF-3. [source] Transcriptional responses of Saccharomyces cerevisiae to preferred and nonpreferred nitrogen sources in glucose-limited chemostat culturesFEMS YEAST RESEARCH, Issue 4 2007Viktor M. Boer Abstract Aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae grown with six different nitrogen sources were subjected to transcriptome analysis. The use of chemostats enabled an analysis of nitrogen-source-dependent transcriptional regulation at a fixed specific growth rate. A selection of preferred (ammonium and asparagine) and nonpreferred (leucine, phenylalanine, methionine and proline) nitrogen sources was investigated. For each nitrogen source, distinct sets of genes were induced or repressed relative to the other five nitrogen sources. In total, 131 such ,signature transcripts' were identified in this study. In addition to signature transcripts, genes were identified that showed a transcriptional coresponse to two or more of the six nitrogen sources. For example, 33 genes were transcriptionally upregulated in leucine-grown, phenylalanine-grown and methionine-grown cultures; this was partly attributed to the involvement of common enzymes in the dissimilation of these amino acids. In addition to specific transcriptional responses elicited by individual nitrogen sources, their impact on global regulatory mechanisms such as nitrogen catabolite repression (NCR) were monitored. NCR-sensitive gene expression in the chemostat cultures showed that ammonium and asparagine were ,rich' nitrogen sources. By this criterion, leucine, proline and methionine were ,poor' nitrogen sources, and phenylalanine showed an ,intermediate' NCR response. [source] Dependence of s -waves on continuous dimension: The quantum oscillator and free systemsFORTSCHRITTE DER PHYSIK/PROGRESS OF PHYSICS, Issue 12 2006K.B. Wolf Abstract Wavefunctions with rotational symmetry (i.e., zero angular momentum) in D dimensions, are called s -waves. In quantum quadratic systems (free particle, harmonic and repulsive oscillators), their radial parts obey Schrödinger equations with a fictitious centrifugal (for integer D , 4) or centripetal (for D = 2) potential. These Hamiltonians close into the three-dimensional Lorentz algebra so(2,1), whose exceptional interval corresponds to the critical range of continuous dimensions 0 < D < 4, where they exhibit a one-parameter family of self-adjoint extensions in ,2(,+). We study the characterization of these extensions in the harmonic oscillator through their spectra which , except for the Friedrichs extension , are not equally spaced, and we build their time evolution Green function. The oscillator is then contracted to the free particle in continuous- D dimensions, where the extension structure is mantained in the limit of continuous spectra. Finally, we compute the free time evolution of the expectation values of the Hamiltonian, dilatation generator, and square radius between three distinct sets of ,heat'-diffused localized eigenstates. This provides a simple group-theoretic description of the purported contraction/expansion of Gaussian-ring s -waves in D > 0 dimensions. [source] Timing and connectivity in the human somatosensory cortex from single trial mass electrical activityHUMAN BRAIN MAPPING, Issue 4 2002Andreas A. Ioannides Abstract Parallel-distributed processing is ubiquitous in the brain but often ignored by experimental designs and methods of analysis, which presuppose sequential and stereotypical brain activations. We introduce here a methodology that can effectively deal with sequential and distributed activity. Regional brain activations elicited by electrical median nerve stimulation are identified in tomographic estimates extracted from single trial magnetoencephalographic signals. Habituation is identified in both primary somatosensory cortex (SI) and secondary somatosensory cortex (SII), often interrupted by resurgence of strong activations. Pattern analysis is used to identify single trials with homogeneous regional brain activations. Common activity patterns with well-defined connectivity are identified within each homogeneous group of single trials across the subjects studied. On the contralateral side one encounters distinct sets of single trials following identical stimuli. We observe in one set of trials sequential activation from SI to SII and insula with onset of SII at 60 msec, whereas in the other set simultaneous early co-activations of the same two areas. Hum. Brain Mapping 15:231,246, 2002. © 2002 Wiley-Liss, Inc. [source] Topology optimization for stationary fluid,structure interaction problems using a new monolithic formulationINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 5 2010Gil Ho Yoon Abstract This paper outlines a new procedure for topology optimization in the steady-state fluid,structure interaction (FSI) problem. A review of current topology optimization methods highlights the difficulties in alternating between the two distinct sets of governing equations for fluid and structure dynamics (hereafter, the fluid and structural equations, respectively) and in imposing coupling boundary conditions between the separated fluid and solid domains. To overcome these difficulties, we propose an alternative monolithic procedure employing a unified domain rather than separated domains, which is not computationally efficient. In the proposed analysis procedure, the spatial differential operator of the fluid and structural equations for a deformed configuration is transformed into that for an undeformed configuration with the help of the deformation gradient tensor. For the coupling boundary conditions, the divergence of the pressure and the Darcy damping force are inserted into the solid and fluid equations, respectively. The proposed method is validated in several benchmark analysis problems. Topology optimization in the FSI problem is then made possible by interpolating Young's modulus, the fluid pressure of the modified solid equation, and the inverse permeability from the damping force with respect to the design variables. Copyright © 2009 John Wiley & Sons, Ltd. [source] Sequential and iterative architectures for distributed model predictive control of nonlinear process systemsAICHE JOURNAL, Issue 8 2010Jinfeng Liu Abstract In this work, we focus on distributed model predictive control of large scale nonlinear process systems in which several distinct sets of manipulated inputs are used to regulate the process. For each set of manipulated inputs, a different model predictive controller is used to compute the control actions, which is able to communicate with the rest of the controllers in making its decisions. Under the assumption that feedback of the state of the process is available to all the distributed controllers at each sampling time and a model of the plant is available, we propose two different distributed model predictive control architectures. In the first architecture, the distributed controllers use a one-directional communication strategy, are evaluated in sequence and each controller is evaluated only once at each sampling time; in the second architecture, the distributed controllers utilize a bi-directional communication strategy, are evaluated in parallel and iterate to improve closed-loop performance. In the design of the distributed model predictive controllers, Lyapunov-based model predictive control techniques are used. To ensure the stability of the closed-loop system, each model predictive controller in both architectures incorporates a stability constraint which is based on a suitable Lyapunov-based controller. We prove that the proposed distributed model predictive control architectures enforce practical stability in the closed-loop system and optimal performance. The theoretical results are illustrated through a catalytic alkylation of benzene process example. © 2010 American Institute of Chemical Engineers AIChE J, 2010 [source] Investigation of cis/trans ratios of peptide bonds in AVP analogues containing N -methylphenylalanine enantiomersJOURNAL OF PEPTIDE SCIENCE, Issue 1 2006Emilia Sikorska Abstract The solution conformation of vasopressin analogues, modified at positions 2 and 3 with N -methylphenylalanine or its enantiomer, [D -MePhe2,MePhe3]AVP and [MePhe2,D -MePhe3]AVP, were studied by 2D NMR spectroscopy in H2O/D2O and theoretical calculations (EDMC/ANALYZE). In the case of [MePhe2,D -MePhe3]AVP, the synthesis afforded two products, A and B, which had identical molecular ions and similar retention times on HPLC. This finding was explained by racemization of Cys1, which gave an additional analogue, [D -Cys1,MePhe2,D -MePhe3]AVP (B). The possibility is not excluded of racemization of Cys1 in the remaining analogues of this series. However, only in the case of [MePhe2,D -MePhe3]AVP was this process so distinct that two strong peaks in the HPLC chromatogram were observed. The NMR spectra of all the analogues showed several distinct sets of residual proton resonances. This suggests that the peptides adopt more than two groups of conformations in H2O/D2O. This fact is due to cis/trans isomerization. Two more populated isomers arise from the cis/trans isomerization across the 2,3 peptide bond in [D -MePhe2,MePhe3]AVP and [MePhe2,D -MePhe3]AVP (A) and across the 1,2 peptide bond in [D -Cys1,MePhe2,D -MePhe3]AVP (B). Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Predictors of clinical outcome in children undergoing orthotopic liver transplantation for acute and chronic liver diseaseLIVER TRANSPLANTATION, Issue 9 2006Chris Rhee The current United Network for Organ Sharing (UNOS) policy is to allocate liver grafts to pediatric patients with chronic liver disease based on the pediatric end-stage liver disease (PELD) scoring system, while children with fulminant hepatic failure may be urgently listed as Status 1a. The objective of this study was to identify pre-transplant variables that influence patient and graft survival in those children undergoing LTx (liver transplantion) for FHF (fulminant hepatic failure) compared to those patients transplanted for extrahepatic biliary atresia (EHBA), a chronic form of liver disease. The UNOS Liver Transplant Registry was examined for pediatric liver transplants performed for FHF and EHBA from 1987 to 2002. Variables that influenced patient and graft survival were assessed using univariate and multivariate analysis. Kaplan-Meier analysis of FHF and EHBA groups revealed that 5 year patient and graft survival were both significantly worse (P < 0.0001) in those patients who underwent transplantation for FHF. Multivariate analysis of 29 variables subsequently revealed distinct sets of factors that influenced patient and graft survival for both FHF and EHBA. These results confirm that separate prioritizing systems for LTx are needed for children with chronic liver disease and FHF; additionally, our findings illustrate that there are unique sets of variables which predict survival following LTx for these two groups. Liver Transpl 12:1347-1356, 2006. © 2006 AASLD. [source] Nitrergic,purinergic interactions in rat distal colon motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2004K. Van Crombruggen Abstract, Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5,-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic,purinergic pathways. Exogenous NO (10,6 to 10,4 mol L,1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+ -sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro- l -arginine methyl ester (l -NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10,3 mol L,1) but did not influence the amplitude. ODQ had no effect. TTX + l -NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP- , -S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5,4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l -NAME, ODQ or RB2. APA shortened the relaxations. l -NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l -NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3,,5,-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations. [source] Priming of plant innate immunity by rhizobacteria and ,-aminobutyric acid: differences and similarities in regulationNEW PHYTOLOGIST, Issue 2 2009Sjoerd Van der Ent Summary ,,Pseudomonas fluorescens WCS417r bacteria and ,-aminobutyric acid can induce disease resistance in Arabidopsis, which is based on priming of defence. ,,In this study, we examined the differences and similarities of WCS417r- and ,-aminobutyric acid-induced priming. ,,Both WCS417r and ,-aminobutyric acid prime for enhanced deposition of callose-rich papillae after infection by the oomycete Hyaloperonospora arabidopsis. This priming is regulated by convergent pathways, which depend on phosphoinositide- and ABA-dependent signalling components. Conversely, induced resistance by WCS417r and ,-aminobutyric acid against the bacterial pathogen Pseudomonas syringae are controlled by distinct NPR1-dependent signalling pathways. As WCS417r and ,-aminobutyric acid prime jasmonate- and salicylate-inducible genes, respectively, we subsequently investigated the role of transcription factors. A quantitative PCR-based genome-wide screen for putative WCS417r- and ,-aminobutyric acid-responsive transcription factor genes revealed distinct sets of priming-responsive genes. Transcriptional analysis of a selection of these genes showed that they can serve as specific markers for priming. Promoter analysis of WRKY genes identified a putative cis -element that is strongly over-represented in promoters of 21 NPR1-dependent, ,-aminobutyric acid-inducible WRKY genes. ,,Our study shows that priming of defence is regulated by different pathways, depending on the inducing agent and the challenging pathogen. Furthermore, we demon-strated that priming is associated with the enhanced expression of transcription factors. [source] |