Functional Plasticity in Oyster Gut Microbiomes along a Eutrophication Gradient in an Urbanized Estuary

Background Oysters in coastal environments are subject to fluctuating environmental conditions that may impact the ecosystem services they provide. Oyster-associated microbiomes are responsible for some of these services, particularly nutrient cycling in benthic habitats. The effects of climate change on host-associated microbiome composition are well-known, but functional changes and how they may impact host physiology and ecosystem functioning are poorly characterized. We investigated how environmental parameters affect oyster-associated microbial community structure and function along a trophic gradient in Narragansett Bay, Rhode Island, USA. Adult eastern oyster, Crassostrea virginica, gut and seawater samples were collected at 5 sites along this estuarine nutrient gradient in August 2017. Samples were analyzed by 16S rRNA gene sequencing to characterize bacterial community structures and metatranscriptomes were sequenced to determine oyster gut microbiome responses to local environments. Results There were significant differences in bacterial community structure between the eastern oyster gut and water samples, suggesting selection of certain taxa by the oyster host. Increasing salinity, pH, and dissolved oxygen, and decreasing nitrate, nitrite and phosphate concentrations were observed along the North to South gradient. Transcriptionally active bacterial taxa were similar for the different sites, but expression of oyster-associated microbial genes involved in nutrient (nitrogen and phosphorus) cycling varied throughout the Bay, reflecting the local nutrient regimes and prevailing environmental conditions. Conclusions The observed shifts in microbial community composition and function inform how estuarine conditions affect host-associated microbiomes and their ecosystem services. As the effects of estuarine acidification are expected to increase due to the combined effects of eutrophication, coastal pollution, and climate change, it is important to determine relationships between host health, microbial community structure, and environmental conditions in benthic communities

Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: An open-label, non-randomised controlled study

OBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D

Variable responses of human and non-human primate gut microbiomes to a Western diet

BACKGROUND: The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. RESULTS: Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. CONCLUSIONS: These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.P40 OD010965 - NIH HHS; P40 RR019963 - NCRR NIH HHS; P51 OD011132 - NIH HHS; R01 RR016300 - NCRR NIH HHS; 5R01RR016300 - NCRR NIH HH

CYK-4 functions independently of its centralspindlin partner ZEN-4 to cellularize oocytes in germline syncytia

International audienceThroughout metazoans, germ cells undergo incomplete cytokinesis to form syncytia connected by intercellular bridges. Gamete formation ultimately requires bridge closure, yet how bridges are reactivated to close is not known. The most conserved bridge component is centralspindlin, a complex of the Rho family GTPase-activating protein (GAP) CYK-4/MgcRacGAP and the microtubule motor ZEN-4/kinesin-6. Here, we show that oocyte production by the syncytial Caenorhabditis elegans germline requires CYK-4 but not ZEN-4, which contrasts with cytokinesis, where both are essential. Longitudinal imaging after conditional inactivation revealed that CYK-4 activity is important for oocyte cellularization, but not for the cytokinesis-like events that generate syncytial compartments. CYK-4's lipid-binding C1 domain and the GTPase-binding interface of its GAP domain were both required to target CYK-4 to intercellular bridges and to cellularize oocytes. These results suggest that the conserved C1-GAP region of CYK-4 constitutes a targeting module required for closure of intercellular bridges in germline syncytia

Translating Evidence-Based Policy to Practice: A Multilevel Partnership Using the Interactive Systems Framework

This is the published version, made available with the permission of the publisher.Despite increases in federal allocations, little is known about how to ensure successful implementation of evidence-based programs. This descriptive case study using the Interactive Systems Framework for Dissemination and Implementation illustrates the Prevention Support System (PSS) implemented for one federal evidence-based policy initiative. Exploring perspectives of intermediary organizations, the article describes the impetus for promoting evidence-based programming, multilevel systemic change, and the collaborations to develop strategic partnerships between national and state entities. Two early adopters, Kansas and Nebraska, illustrate the general capacity-building technical assistance activities conducted to build a multilevel PSS. The article concludes with outcomes, lessons learned, and recommendations for building stronger implementation capacity

Mechanism of Ad5 Vaccine Immunity and Toxicity: Fiber Shaft Targeting of Dendritic Cells

Recombinant adenoviral (rAd) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5) vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs) was independent of the coxsackievirus and adenovirus receptor (CAR), its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines

Establishing intra- and inter-rater agreement of the Face, Legs, Activity, Cry, Consolability scale for evaluating pain in toddlers during immunization

BACKGROUND: The Face, Legs, Activity, Cry, Consolability (FLACC) scale is a five-item tool that was developed to assess postoperative pain in young children. The tool is frequently used as an outcome measure in studies investigating acute procedural pain in young children; however, there are limited published psychometric data in this context. OBJECTIVE: To establish inter-rater and intrarater agreement of the FLACC scale in toddlers during immunization. METHODS: Participants comprised a convenience sample of toddlers recruited from an immunization drop-in service, who were part of a larger pilot randomized controlled trial. Toddlers were video- and audiotaped during immunization procedures. The first rater scored each video twice in random order over a period of three weeks (intrarater agreement), while the second rater scored each video once and was blinded to the first rater\u27s scores (inter-rater agreement). The FLACC scale was scored at four timepoints throughout the procedure. Intraclass correlation coefficients were used to assess agreement of the FLACC scale. RESULTS: Thirty toddlers between 12 and 18 months of age were recruited, and video data were available for 29. Intrarater agreement coefficients were 0.88 at baseline, 0.97 at insertion of first needle, and 0.80 and 0.81 at 15 s and 30 s following the final injection, respectively. Inter-rater coefficients were 0.40 at baseline, 0.95 at insertion of first needle, and 0.81 and 0.78 at 15 s and 30 s following the final injection, respectively. CONCLUSIONS: The FLACC scale has sufficient agreement in assessing pain in toddlers during immunizations, especially during the most painful periods of the procedure

Cytological and transcript analyses reveal fat and lazy persister-like bacilli in tuberculous sputum

As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis

Biodiversity of protists and nematodes in the wild nonhuman primate gut

Documenting the natural diversity of eukaryotic organisms in the nonhuman primate (NHP) gut is important for understanding the evolution of the mammalian gut microbiome, its role in digestion, health and disease, and the consequences of anthropogenic change on primate biology and conservation. Despite the ecological significance of gut-associated eukaryotes, little is known about the factors that influence their assembly and diversity in mammals. In this study, we used an 18S rRNA gene fragment metabarcoding approach to assess the eukaryotic assemblage of 62 individuals representing 16 NHP species. We find that cercopithecoids, and especially the cercopithecines, have substantially higher alpha diversity than other NHP groups. Gut-associated protists and nematodes are widespread among NHPs, consistent with their ancient association with NHP hosts. However, we do not find a consistent signal of phylosymbiosis or host-species specificity. Rather, gut eukaryotes are only weakly structured by primate phylogeny with minimal signal from diet, in contrast to previous reports of NHP gut bacteria. The results of this study indicate that gut-associated eukaryotes offer different information than gut-associated bacteria and add to our understanding of the structure of the gut microbiome.Fil: Mann, Allison E.. University of British Columbia; CanadáFil: Mazel, Florent. University of British Columbia; CanadáFil: Lemay, Matthew A.. University of British Columbia; CanadáFil: Morien, Evan. University of British Columbia; CanadáFil: Billy, Vincent. University of British Columbia; CanadáFil: Kowalewski, Miguel Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Biológica de Usos Múltiples (Sede Corrientes); ArgentinaFil: Di Fiore, Anthony. University of Texas at Austin; Estados UnidosFil: Link, Andrés. Universidad de los Andes; ColombiaFil: Goldberg, Tony L.. University of Wisconsin; Estados UnidosFil: Tecot, Stacey. University of Arizona; Estados UnidosFil: Baden, Andrea L.. City University Of New York. Hunter College; Estados UnidosFil: Gomez, Andres. University of Minnesota; Estados UnidosFil: Sauther, Michelle L.. State University of Colorado at Boulder; Estados UnidosFil: Cuozzo, Frank P.. Lajuma Research Centre; SudáfricaFil: Rice, Gillian A. O.. Dartmouth College; Estados UnidosFil: Dominy, Nathaniel J.. Dartmouth College; Estados UnidosFil: Stumpf, Rebecca. University of Illinois at Urbana; Estados UnidosFil: Lewis, Rebecca J.. University of Texas at Austin; Estados UnidosFil: Swedell, Larissa. University of Cape Town; Sudáfrica. City University of New York; Estados UnidosFil: Amato, Katherine. Northwestern University; Estados UnidosFil: Wegener Parfrey, Laura. University of British Columbia; Canad