Membrane repair against H. pylori promotes cancer cell proliferation

Membrane repair is a universal response against physical and biological insults and enables cell survival. Helicobacter pylori is one of the most common human pathogens and the first formally recognized bacterial carcinogen associated with gastric cancer. However, little is known about host membrane repair in the context of H. pylori infection. Here we show that H. pylori disrupts the host plasma membrane and induces Ca2+ influx, which triggers the translocation of annexin family members A1 and A4 to the plasma membrane. This in turn activates a membrane repair response through the recruitment of lysosomal membranes and the induction of downstream signaling transduction pathways that promote cell survival and proliferation. Based on our data, we propose a new model by which H. pylori infection activates annexin A1 and A4 for membrane repair and how annexin A4 over-expression induced signaling promotes cell proliferation. Continual activation of this membrane repair response signaling cascade may cause abnormal cellular states leading to carcinogenesis. This study links H. pylori infection to membrane repair, providing insight into potential mechanisms of carcinogenesis resulting from membrane damage

Minimal effect of sleep on the risk of age-related macular degeneration: a Mendelian randomization study

AimsObservational studies have shown that sleep pattern is associated with age-related macular degeneration (AMD), but whether sleep pattern is a causal factor for AMD remains unclear. This study aims to use Mendelian randomization (MR) analysis to investigate the potential causal relationship between sleep traits and AMD.MethodsThis is a two-sample MR study. The single-nucleotide polymorphisms associated with AMD and early AMD were selected as the outcome from two different genome-wide association studies (GWAS): the early AMD GWAS with 14,034 cases and 91,214 controls, and AMD GWAS with 3,553 cases and 147,089 controls. The datasets of sleep duration, daytime dozing, and sleeplessness were used as exposure, which comprised nearly 0.46 million participants. Inverse-variance weighted method was used as the main result, and comprehensive sensitivity analyses were conducted to estimate the robustness of identified associations and the impact of potential horizontal pleiotropy.ResultsThrough MR analysis, we found that sleep duration was significantly associated with AMD (OR = 0.983, 95% CI = 0.970–0.996, P-value = 0.01). We also found suggestive evidence for the association of genetically predicted sleep duration with early AMD, which showed a consistent direction of effect with a marginal significance (OR = 0.724, 95% CI = 0.503–1.041, P-value = 0.08). Sensitivity analyses further supported the robustness of the causal relationship between sleep duration and AMD. However, we were unable to determine the relationship between daytime dozing or sleeplessness and AMD (including early AMD) (P-value > 0.05).ConclusionSleep duration affects the causal risk for AMD; that is, longer sleep duration reduces the risk of AMD, while shorter sleep duration increases the risk of AMD. Although the influence is minimal, keeping adequate sleep duration is recommended, especially for patients with intermediate or advanced AMD

Mutagenesis of the fusion peptide-like domain of hepatitis C virus E1 glycoprotein: involvement in cell fusion and virus entry

<p>Abstract</p> <p>Background</p> <p>Envelope (E) glycoprotein E2 of the hepatitis C virus (HCV) mediates binding of the virus to target cell receptors. Nevertheless, the precise role of E1 in viral entry remains elusive.</p> <p>Methods</p> <p>To understand the involvement of the fusion peptide-like domain positioned at residues 264 to 290 within envelope glycoprotein E1 in HCV infection, mutants with Ala and Asn substitutions for residues conserved between HCV and E proteins of flaviviruses or the fusion proteins of paramyxoviruses were constructed by site-directed mutagenesis and their effects on membrane fusion and viral infectivity were examined.</p> <p>Results</p> <p>None of these mutations affected the synthesis or cell surface expression of envelope proteins, nor did they alter the formation of a non-covalent E1-E2 heterodimer or E2 binding to the large extracellular loop of CD81. The Cys residues located at positions 272 and 281 were unlikely involved in intra- or intermolecular disulfide bond formation. With the exception of the G267A mutant, which showed increased cell fusion, other mutants displayed reduced or marginally inhibited cell fusion capacities compared to the wild-type (WT) E1E2. The G267A mutant was also an exception in human immunodeficiency virus type 1 (HIV-1)/HCV E1E2 pseudotyping analyses, in that it showed higher one-cycle infectivity; all other mutants exhibited greatly or partially reduced viral entry versus the WT pseudotype. All but the G278A and D279N mutants showed a WT-like profile of E1E2 incorporation into HIV-1 particles. Since C272A, C281A, G282A, and G288A pseudotypes bound to Huh7 cells as effectively as did the WT pseudotype, the reduced infectivity of these pseudotypes was due to their ability to inhibit cell fusion.</p> <p>Conclusion</p> <p>Our results indicate that specific residues, but not the structure, of this fusion peptide-like domain are required for mediating cell fusion and viral entry.</p

Effect of Oral Administration of Enterococcus faecium Ef1 on Innate Immunity of Sucking Piglets

The objective of this study was to evaluate the effect of orally administered Enterococcus faecium EF1 on innate immune responses of jejunal mucosa in newborn piglets. Twenty-four commercial crossbred healthy newborn piglets were randomly divided into two groups, control (T0) and treatment (T1) group. Each group consists of 12 piglets. T1 was administered sterilized skim milk 2 ml piglet-1 day-1 with addition of E. faecium EF1 (5~6×108 cfu/ml) by oral gavage on alternative odd days (1st, 3rd and 5th) after birth. T0 fed with the same volume of sterilized skim milk without probiotics. The merciful killing of piglets at the 25th day after birth was performed to collect the samples of jejunal mucosa to measure the innate cytokine responses and the Toll-like receptors gene expression by quantitative real time PCR. The results showed that TGF-β1 and TNF-α concentrations increased and mRNA expression levels also improved significantly in T1 as compared to T0. While, the production of IFN-γ and IL-8 decreased significantly in T1 and gene expression modification was not observed. In addition, TLR (Toll-like receptor) 2 and TLR 9 transcription levels were up-regulated in treatment (T1) group. These findings revealed that oral administration of E. faecium EF1 was effective to activate innate immunity and could modulate the TLRs expression in jejunal mucosa of piglets

Semileptonic B(Bs,Bc)B(B_s, B_c) decays in the light-cone QCD sum rules

Semileptonic $B$($B_s, B_c$) decays are investigated systematically in the light-cone QCD sum rules. Special emphasis is put on the LCSR calculation on weak form factors with an adequate chiral current correlator, which turns out to be particularly effective to control the pollution by higher twist components of spectator mesons. The result for each channel depends on the distribution amplitude of the the producing meson. The leading twist distribution amplitudes of the related heavy mesons and charmonium are worked out by a model approach in the reasonable way. A practical scenario is suggested to understand the behavior of weak form factors in the whole kinematically accessible ranges. The decay widths and branching ratios are estimated for several $B$($B_c$) decay modes of current interest.Comment: 8 pages, talk given by the first arthur at 4th International Conference on Flavor Physics (ICFP 2007), Beijing, China, Sept 24-28, 200

Temporally Guided Music-to-Body-Movement Generation

This paper presents a neural network model to generate virtual violinist's 3-D skeleton movements from music audio. Improved from the conventional recurrent neural network models for generating 2-D skeleton data in previous works, the proposed model incorporates an encoder-decoder architecture, as well as the self-attention mechanism to model the complicated dynamics in body movement sequences. To facilitate the optimization of self-attention model, beat tracking is applied to determine effective sizes and boundaries of the training examples. The decoder is accompanied with a refining network and a bowing attack inference mechanism to emphasize the right-hand behavior and bowing attack timing. Both objective and subjective evaluations reveal that the proposed model outperforms the state-of-the-art methods. To the best of our knowledge, this work represents the first attempt to generate 3-D violinists' body movements considering key features in musical body movement

Investigating the Knowledge-Sharing Behavior ina Professional Virtual Community

This research aims at investigating the knowledge sharing-behaviors in a teachers’ professional virtual community. Logs data in the entire community and in special interest groups (SIGs) were analyzed. Some typical behaviors were identified by the clustering analysis in this study. The largest group of member belongs to inactive users. They rarely log in the system, are passive in uploading or downloading teaching materials, and almost never post or reply messages. Another group is active in receiving knowledge while reluctant to give knowledge or to respond. The third group frequently login the system, is the most active in sharing knowledge, and actively searching knowledge. However, the third group contains only a small number of members. Furthermore, fifty-five members of the knowledge-sharing group were interviewed using focus group technique to find out qualitative information as to why they are willing to share information and what are their concerns in sharing information. The results indicated that knowledge sharing is not a common behavior in professional virtual community, and knowledge-sharing culture is difficult to promote even in non-competitive professional communities. Secondly, knowledge cannot flow easily throughout the community even when certain knowledge flow promoting mechanism is provided. Thirdly, professional autonomy may hinder the frequency of interactions with others in professional virtual community. Fourthly, attitudes regarding information ownership are important factors in knowledge sharing of a professional virtual community. Finally, teaching and IT usage experiences are not major factors affecting knowledge-sharing behavior in pro fessional virtual communities