Vibrio parahaemolyticus is a renowned enteropathogen known for infecting humans. The infection usually involves various genes which help bacterium bypass the immune system of the host. Type III secretion system (T3SS) is an essential factor for the infection. The present study introduces the probable structure of VopJ, a T3SS effector of V. parahaemolyticus. The vopJ gene was amplified and sequenced from V. parahaemolyticus. The model generated through homology modelling showed a Z score of around 2.5, which fits quite near in the standard model available in the databases. The model has only a couple of outlier amino acids, which indicate a good fit of the model. Docking studies with small molecules like Acetyl-CoA, Inositol hexakisphosphate, GTP, and AMP have shown negative ΔG - 10.49, -52.80, -8.36 and -9.02, respectively, which indicates spontaneous binding. The molecular simulation studies have also supported the binding with a low RMSD value of less than 0.5 nm. The RMSF values obtained using the modelling were also quite low (>0.35 nm), which indicates the consistency achieved using the docking studies. These small molecules are very crucial in the MAPK pathways, which is essential for the immune response from the host cell. This effector can thus have an ability to highjack the immune system and help the bacterium in the potent infection. Up to our understanding, this is the first report which describes the in-silico model to understand the mode of infection of T3SS in enteropathogen V. parahaemolyticus. Communicated by Ramaswamy H. Sarma.Heterosexual sex, foremost its gender-power dynamics, is embedded in and informed by the socio-historical context in which it occurs. While safer sexual communication skills are well documented as key to the success of sexual and reproductive health programming and education, communication skills about the positive aspects of sexuality such as sexual pleasure are often limited if not absent. Using data from in-depth qualitative interviews with men and women aged 26-39 from a diverse set of backgrounds in Cape Town, South Africa, this study examines the ways in which gender-power dynamics manifest in negotiations of HIV and pregnancy prevention and sexual pleasure in the intimate spaces of heterosex. Findings fall under three themes 1) condom negotiation as a replacement for other aspects of sexual communication; 2) self-efficacy in negotiating prevention and negotiating one’s own sexual pleasure; and 3) the integral role men play in heterosexual encounters in the facilitation of women’s sexual autonomy and women’s sexual pleasure. This study contributes to research not only examining the positive and more nuanced realities of heterosex in the South African context, but also argues for the need to integrate positive aspects of sexuality into sexual and reproductive health programming in general.Cyclic adenosine monophosphate-response element (CREB)-binding protein (CBP) and EP300E1A-binding protein (p300) are members of the bromodomain and extraterminal motif (BET) family. These highly homologous proteins have a key role in modulating transcription, including altering the status of chromatin or through interactions with or posttranslational modifications of transcription factors. As CBP and p300 have known roles for stimulating c-Myc oncogenic activity, a small-molecule inhibitor, GNE-781, was developed to selectively and potently inhibit the CBP/p300 bromodomains (BRDs). Genetic models have been challenging to develop due to embryonic lethality arising from germline homozygous mutations in either CBP or P300. Hence, the purpose of this study was to characterize the role of dual inhibition of these proteins in adult rats and dogs. Repeat dose toxicity studies were conducted, and toxicologic and pathologic end points were assessed. GNE-781 was generally tolerated; however, marked effects on thrombopoiesis occurred in both species. Evidence of inhibition of erythroid, granulocytic, and lymphoid cell differentiation was also present, as well as deleterious changes in gastrointestinal and reproductive tissues. These findings are consistent with many preclinical (and clinical) effects reported with BET inhibitors targeting BRD proteins; thus, the current study findings indicate a likely important role for CBP/p300 in stem cell differentiation.Background The proportion of frailty in older adults is increasing in many countries. This is predicted to result in an increased demand rapidly for long-term care. Demand for institutional long-term care followed by an increasing globally.Aims This study was to review the evidence regarding the effects of leisure-time physical activity (LTPA) interventions on frail older adults in long-term care facilities (LTCFs) with regard to frailty-related characteristics of randomized controlled trials.Design A literature searches of the published articles indexed in CINAHL, MEDLINE, PsycINFO, ProQuest, and Google Scholar between 2000 and 2017 was conducted, and seven articles were included in this investigation.Methods The inclusion criteria were divided into four sections (1) design randomized controlled trials (RCTs); (2) sample population LTCF adults aged 60 years or over with frailty; (3) intervention LTPA; and (4) body composition physical, functional or neuropsychological tests as either the primary or the seconuration and frequency is crucial. This review provides support for frail older adults in LTCFs to develop suitable and safe LTPA.In this study, we investigated the effects of modeling type and reflection on the acquisition of dart-throwing skills, self-efficacy beliefs and self-reaction scores by conceptually replicating a study by Kitsantas, Zimmerman, and Cleary (2000). Participants observing a novice model were expected to surpass participants observing an expert model who in turn were expected to outperform participants who learned without a model. Reflection was hypothesized to have a positive effect. 156 High school and university students were tested three times in a pretest, after a modeling intervention, and after a practice round. Contrary to what was expected, we found no main effects of modeling type and reflection. No interaction effects were found either. There was an effect of testing moment, indicating that participants improved dart-throwing skills, self-efficacy beliefs, and self-reaction scores over time. With these findings, we are not able to replicate Kitsantas et al. From our study, we conclude that observational learning, irrespective of the model’s skill level, combined with physical practice, yields similar results as mere physical practice.The epithelium adjacent to an oral squamous cell carcinoma is at risk of undergoing precancerous changes. Even after such changes occur, however, the adjacent epithelium remains histologically similar to normal mucosa. We investigated five argyrophilic nucleolar organizer region (AgNOR)-related features in samples of oral verrucous carcinoma (VeCa) and their corresponding adjacent lining epithelium (adj. VeCa). Morphometric characteristics of AgNORs in oral adj. VeCa and oral VeCa were compared to normal mucosa epithelium, squamous cell carcinoma and oral mucosa epithelium adjacent to squamous cell carcinoma findings that we published earlier. Although adj. VeCa and normal oral mucosa were histologically similar, total AgNOR volume differentiated adj. VeCa from normal oral mucosa, but revealed no significant difference between VeCa and adj. VeCa. Total AgNOR volume/nuclear volume discriminated VeCa from adj. VeCa and normal oral mucosa. Certain AgNOR parameters provide a complementary tool for discriminating VeCa from adj. VeCa and normal oral mucosa, and also for detecting incipient malignant changes in epithelium adjacent to VeCa. Use of the AgNOR technique is cost-effective, because it can be performed on paraffin sections.Common wisdom suggests that older is wiser. Consequently, people rarely give advice to older individuals-even when they are relatively more expert-leading to missed learning opportunities. Across six studies (N = 3,445), we explore the psychology of advisers when they are younger (reverse advising), the same age (peer advising), or older (traditional advising) than their advisees. Study 1 shows that advisers avoid reverse-advising interactions because they perceive that their relative youth makes them less effective. However, when compared to advisees’ actual perceptions, reverse advisers are misguided, as they underestimate their effectiveness when giving general life advice (Study 2a-2b) as well as tactical advice (Studies 3-4). This misperception is in part driven by advisers’ beliefs about their own competence and others’ receptivity. Finally, we demonstrate an intervention that mitigates advisers’ misguided beliefs (Study 5). Contrary to advisers’ own perceptions and popular belief, these findings illustrate that being relatively young can also mean being an impactful adviser.Nonclinical immunotoxicity evaluation is an important component of safety assessment for pharmaceuticals. One in vitro assay that can be applied in a weight of evidence assessment is the human lymphocyte activation (HuLA) assay, an antigen recall assay, similar in many respects to the in vivo T-cell-dependent antibody response (TDAR) in that cooperation of multiple immune cell types are needed to produce responses. This assay uses human cells and is more amenable than the TDAR to compound ranking and mechanistic studies. The HuLA assay requires less time and drug than TDAR assays, uses a relevant antigen (influenza), reflects a human immune response, and applies principles of the 3Rs to non-clinical safety assessment. Peripheral blood mononuclear cells (PBMC) from flu-immunized donors are re-stimulated with flu-vaccine in the presence of test articles, and proliferation is measured. Published data demonstrate the applicability of the HuLA assay, but it has not been evaluated for reproducibility across testing sites. To evaluate assay reproducibility, scientists from a consortium of institutions conducted the assay in parallel, using a common pool of donor PBMC, influenza vaccine, and known immunosuppressant compounds (cyclosporine A and mycophenolic acid). The HuLA assay was highly reproducible in identification of inhibition of antigen-specific responses, and there was significant agreement across testing sites in the half maximal inhibitory concentration (IC50) values. Intra-site variability was the largest contributor to the variability observed within the assay. The HuLA assay was demonstrated to be ideally suited to comparing multiple compounds (i.e. compound ranking or benchmarking) within the same assay. Overall, the data reported herein support the HuLA assay as a useful tool in mechanistic evaluations of antigen-specific immune responses.Introduction Epigenetic modification is a type of gene expression and regulation that does not involve changes in DNA sequences. An increasing number of studies have proven that epigenetic modifications play an important role in the occurrence and progression of liver diseases through the gene regulation and protein expressions of hepatocellular lipid metabolism, inflammatory reaction, cell proliferation, and activation, etc.Areas covered In this study, we elaborated and analyzed the underlying functional mechanism of epigenetic modification in alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver fibrosis (LF), viral hepatitis, hepatocellular carcinoma (HCC), and research progress of recent years.Expert opinion The further understanding of epigenetic mechanisms that can regulate gene expression and cell phenotype leads to new insights in epigenetic control of chronic liver disease. Currently, hepatologists are exploring the role of DNA methylation, histone/chromatin modification, and non-coding RNA in specific liver pathology.