Sulfur Tolerant Pd/Cu and Pd/Au Alloy Membranes for H2 Separation with High Pressure CO2 for Sequestration

The effect of H{sub 2}S poisoning on Pd, Pd/Cu, and Pd/Au alloy composite membranes prepared by the electroless deposition method on porous Inconel supports was investigated to provide a fundamental understanding of the durability and preparation of sulfur tolerant membranes. X-ray photoelectron spectroscopy (XPS) studies showed that the exposure of pure Pd to 50 ppm H{sub 2}S/H{sub 2} mixtures caused bulk sulfide formation at lower temperatures and surface sulfide formation at higher temperatures. Lower temperatures, longer exposure times, and higher H{sub 2}S concentrations resulted in a higher degree of sulfidation. In a Pd membrane, the bulk sulfide formation caused a drastic irrecoverable H{sub 2} permeance decline and an irreparable loss in selectivity. Pd/Cu and Pd/Au alloy membranes exhibited permeance declines due to surface sulfide formation upon exposure to 50 ppm H{sub 2}S/H{sub 2} gas mixtures. However in contrast to the pure Pd membrane, the permeances of the Pd/Cu and Pd/Au alloy membranes were mostly recovered in pure H{sub 2} and the selectivity of the Pd alloy layers remained essentially intact throughout the characterization in H{sub 2}, He and H{sub 2}S/H{sub 2} mixtures which lasted several thousand hours. The amount of irreversible sulfur poisoning decreased with increasing temperature due to the exothermicity of H{sub 2}S adsorption. Longer exposure times increased the amount of irreversible poisoning of the Pd/Cu membrane but not the Pd/Au membrane. Pd/Au coupon studies of the galvanic displacement method showed that higher Au{sup 3+} concentrations, lower pH values, higher bath temperatures and stirring the bath at a rate of 200 rpm yielded faster displacement rates, more uniform depositions, and a higher Au content within the layers. While 400 C was found to be sufficient to form a Pd/Au alloy on the surface, high temperature X-ray diffraction (HTXRD) studies showed that even after annealing between 500-600 C, the Pd/Cu alloys could have part or all of the surface in the less sulfur resistant {beta} phase

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle

<p>Abstract</p> <p>Background</p> <p>D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis.</p> <p>Methods</p> <p>By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels.</p> <p>Results</p> <p>IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited.</p> <p>Conclusion</p> <p>Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.</p

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

Objective: To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2). Design: We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-Analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-Analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as â € positive' and â € less-credible positive' were further validated in three large GWAS consortia conducted in populations of European origin. Results: We initially identified 18 independent variants at 16 loci that were classified as â € positive' polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as â € less-credible positive' SNPs; 72.2% of the â € positive' SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to â € less-credible' positive (reducing the â € positive' variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-Analyses found no evidence to support their associations with CRC risk. Conclusion: The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.</p

Increased Vascularity in Cervicovaginal Mucosa with Schistosoma haematobium Infection

Schistosomiasis is a fresh water parasite infection that affects millions of people, especially in Africa. Recent knowledge about the genital manifestations of schistosomiasis; especially its possible association with human immunodeficiency virus (HIV) infection, has led to increased focus on this neglected tropical disease. Millions of women remain undiagnosed for genital schistosomiasis, and may suffer from abnormal mucosal blood vessels, contact bleeding and lesions named sandy patches. This study analyses a unique selection of female genital biopsies containing parasite eggs. Protein detection and standard histopathological assessment are combined to quantify and study the characteristics of the mucosal blood vessels surrounding the eggs. Our results show that the genital mucosa with parasite eggs is more vascularised compared to healthy tissue, and that viable eggs tend to be surrounded by proliferating blood vessels. These findings have not yet been correlated directly to clinical manifestations. Further studies are needed in order to provide clinical advice on the risks and consequences of mucosal lesions particular to female genital schistosomiasis

Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy

It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000 CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816 CpGs) versus earlier loading (9,153 CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive to acute exercise demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/memory

Single Molecule Analysis of Replicated DNA Reveals the Usage of Multiple KSHV Genome Regions for Latent Replication

Kaposi's sarcoma associated herpesvirus (KSHV), an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA). Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD). Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR) plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA sequences

Advantage of Hole Stimulus in Rivalry Competition

Mounting psychophysical evidence suggests that early visual computations are sensitive to the topological properties of stimuli, such as the determination of whether the object has a hole or not. Previous studies have demonstrated that the hole feature took some advantages during conscious perception. In this study, we investigate whether there exists a privileged processing for hole stimuli during unconscious perception. By applying a continuous flash suppression paradigm, the target was gradually introduced to one eye to compete against a flashed full contrast Mondrian pattern which was presented to the other eye. This method ensured that the target image was suppressed during the initial perceptual period. We compared the initial suppressed duration between the stimuli with and without the hole feature and found that hole stimuli required less time than no-hole stimuli to gain dominance against the identical suppression noise. These results suggest the hole feature could be processed in the absence of awareness, and there exists a privileged detection of hole stimuli during suppressed phase in the interocular rivalry