Contacts between the endoplasmic reticulum and other membranes in neurons

The cytoplasm of eukaryotic cells is compartmentalized by intracellular membranes that define subcellular organelles. One of these organelles, the endoplasmic reticulum, forms a continuous network of tubules and cisternae that extends throughout all cell compartments, including neuronal dendrites and axons. This network communicates with most other organelles by vesicular transport, and also by contacts that do not lead to fusion but allow cross-talk between adjacent bilayers. Though these membrane contacts have previously been observed in neurons, their distribution and abundance has not been systematically analyzed. Here, we have carried out such analysis. Our studies reveal new aspects of the internal structure of neurons and provide a critical complement to information about interorganelle communication emerging from functional and biochemical studies

How do organisms affect and respond to climate change?

Life on Earth is diverse at many levels, meaning there is a lot of variety within species and there are many different kinds of species. This biodiversity provides many of the resources that humans need and enhances our quality of life. All of Earth’s organisms are affected by Earth’s climate, but they also influence Earth’s climate. In this article, we show how research on plants, animals, and microbes helps us better understand how living things can both impact and respond to climate change. This research also gives us insight into what the future might be like for life on Earth. Such knowledge will help us to protect our planet—and the living things on it—from the harmful effects of future climate change

Anti-HIV Activity in Cervical-Vaginal Secretions from HIV-Positive and -Negative Women Correlate with Innate Antimicrobial Levels and IgG Antibodies

We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(−) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (−) women inhibit HIV infection. indicated that each was present in CVL from HIV(+) and HIV(−) women. HBD2 and MIP3α correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+) women.These findings indicate that CVL from healthy HIV(+) and HIV(−) women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women

Anti-HIV Activity in Cervical-Vaginal Secretions from HIV-Positive and -Negative Women Correlate with Innate Antimicrobial Levels and IgG Antibodies

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection. Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti- HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti- gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+) women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(2) controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5- tropic, mucosally-transmitted founder virus) viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3a indicated that each was present in CVL from HIV(+) and HIV(2) women. HBD2 and MIP3a correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+) women. Conclusions/Significance: These findings indicate that CVL from healthy HIV(+) and HIV(2) women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV- specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women

Crowdsourcing to develop open-access learning resources on antimicrobial resistance

Objectives Antimicrobial resistance (AMR) is a significant threat to global public health. Many medical curricula have limited clinical cases and materials focused on AMR, yet enhanced AMR education and training are needed to support antimicrobial stewardship programmes. We used crowdsourcing methods to develop open-access, learner-centred AMR resources. Crowdsourcing is the process of having a large group, including experts and non-experts, solve a problem and then share solutions with the public. Methods We organised a global crowdsourcing contest soliciting AMR-related multiple-choice questions, infographics, and images. First, we convened a diverse steering committee group to finalise a call for entries. Second, we launched the contest and disseminated the call for entries using social media, blog posts, email, and an in-person event. Partner institutions included two digital healthcare platforms: Figure 1® and Ding Xiang Yuan. Both organizations serve as online communities for healthcare specialists and professionals to report and comment on clinical information. At the end of the call, solicited entries were screened for eligibility and judged on merit and relevance to AMR learning and education. Exceptional entries were recognised, awarded prizes, and further reviewed for sharing with the public via open-access platforms. Results We received 59 entries from nine countries. These included 54 multiple-choice questions, four infographics, and one image. Eligible entries (n = 56) were reviewed and assigned a score on a 1-10 scale. Eight entries received mean scores greater than 6.0 and were selected as finalists. The eight finalist entries consisted of three infographics and five multiple-choice questions. They were disseminated through open-access publications and online medical communities. Although we launched a global call, we relied heavily on medical student groups and the entries received were not entirely globally representative. Conclusions We demonstrate that crowdsourcing challenge contests can be used to identify infectious disease teaching materials. Medical educators and curriculum developers can adapt this method to solicit additional teaching content for medical students

Inflammatory Bowel Diseases Phenotype, C. difficile and NOD2 Genotype Are Associated with Shifts in Human Ileum Associated Microbial Composition

We tested the hypothesis that Crohn’s disease (CD)-related genetic polymorphisms involved in host innate immunity are associated with shifts in human ileum–associated microbial composition in a cross-sectional analysis of human ileal samples. Sanger sequencing of the bacterial 16S ribosomal RNA (rRNA) gene and 454 sequencing of 16S rRNA gene hypervariable regions (V1–V3 and V3–V5), were conducted on macroscopically disease-unaffected ileal biopsies collected from 52 ileal CD, 58 ulcerative colitis and 60 control patients without inflammatory bowel diseases (IBD) undergoing initial surgical resection. These subjects also were genotyped for the three major NOD2 risk alleles (Leu1007fs, R708W, G908R) and the ATG16L1 risk allele (T300A). The samples were linked to clinical metadata, including body mass index, smoking status and Clostridia difficile infection. The sequences were classified into seven phyla/subphyla categories using the Naïve Bayesian Classifier of the Ribosome Database Project. Centered log ratio transformation of six predominant categories was included as the dependent variable in the permutation based MANCOVA for the overall composition with stepwise variable selection. Polymerase chain reaction (PCR) assays were conducted to measure the relative frequencies of the Clostridium coccoides – Eubacterium rectales group and the Faecalibacterium prausnitzii spp. Empiric logit transformations of the relative frequencies of these two microbial groups were included in permutation-based ANCOVA. Regardless of sequencing method, IBD phenotype, Clostridia difficile and NOD2 genotype were selected as associated (FDR ≤0.05) with shifts in overall microbial composition. IBD phenotype and NOD2 genotype were also selected as associated with shifts in the relative frequency of the C. coccoides – E. rectales group. IBD phenotype, smoking and IBD medications were selected as associated with shifts in the relative frequency of F. prausnitzii spp. These results indicate that the effects of genetic and environmental factors on IBD are mediated at least in part by the enteric microbiota