Gene Loss and Adaptation to Hominids Underlie the Ancient Origin of HIV-1

SummaryHIV-1 resulted from cross-species transmission of SIVcpz, a simian immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a recombinant between two SIV lineages from Old World monkeys. Lentiviral interspecies transmissions are partly driven by the evolution and capacity of viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz. This genomic deletion resulted in the reconstruction of the overlapping vif gene by “overprinting,” creating a unique vif that overlaps in its 3′ end with the vpr gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1 originated through a series of gene loss and adaptation events that generated its chimpanzee precursor and lowered the species barrier to human infection

Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the human Gastrointestinal Tract

Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis

Virtual reality and psychoeducation to reduce preoperative anxiety in oncology patients: Protocol of a randomized controlled trial

peer reviewedBackground. Many women with breast cancer who are scheduled for surgery suffer from preoperative anxiety (Majumdar et al., 2019). Unmanaged preoperative anxiety can have a negative impact on the intra- and postoperative periods (e.g., pain, increased use of analgesics and anesthetics) (Kulkarni et al., 2017; Stamenkovic et al., 2018). The present study aims to examine the benefit of the combination of two psychological tools during the preoperative phase: psychoeducation on relaxation and relaxing environments through virtual reality (VR). Methods. One hundred and twenty women with breast cancer undergoing initial surgery will be enrolled in this single-center, three-arm randomized controlled trial. Patients will be randomized at 1:1:1 ratio to one of the following groups: psychoeducation + VR; only psychoeducation; control group receiving standard treatment. Primary outcomes are preoperative anxiety, worries, and relaxation's indicators measured by visual analog scales. Secondary clinical outcomes are perioperative experience (e.g., pain, comfort), heart rate, anesthesic and surgical data (e.g., anesthesia and analgesia requirement). Data will be collected at baseline, 21 days before surgery (T1), 14 days before surgery (T2), 7 days before surgery (T3), the day of surgery (T4), the day after surgery (T5), and ∼1 month after surgery (T6). Expected results. We should observe a significant difference between the outcomes of the two experimental groups and those of the control group (i.e., decrease in preoperative anxiety and worry, improvement in relaxation and perioperative experience). Furthermore, VR immersions could enhance the relaxation learning. Thus, we should also observe a significant difference between the results of this group and the group receiving psychoeducation only. Discussion. The combined action of psychoeducation and VR could become a real alternative to reduce anxiety in women awaiting for breast cancer surgery. This new proactive approach may provide a much-needed, easy-to-use, non-pharmacological relaxation intervention to improve the health of surgical patients

Interactions with M Cells and Macrophages as Key Steps in the Pathogenesis of Enterohemorragic Escherichia coli Infections

Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause serious infections ranging from diarrhea to hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut lumen to underlying tissues is a decisive step in the development of the infection, but the mechanisms involved remain unclear. Many bacterial pathogens target the follicle-associated epithelium, which overlies Peyer's patches (PPs), cross the intestinal barrier through M cells and are captured by mucosal macrophages. Here, translocation across M cells, as well as survival and proliferation of EHEC strains within THP-1 macrophages were investigated using EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains are able to interact in vivo with murine PPs, to translocate ex vivo through murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC strains are also able to survive and to produce Stx in macrophages, which induce cell apoptosis and Stx release. In conclusion, our results suggest that the uptake of EHEC by M cells and underlying macrophages in the PP may be a critical step in Stx translocation and release in vivo. A new model for EHEC infection in humans is proposed that could help in a fuller understanding of EHEC-associated diseases

Using metabarcoding to reveal and quantify plant-pollinator interactions.

12 pagesInternational audienceGiven the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole

Experimental models to study intestinal microbes-mucus interactions in health and disease

A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the gut microbiota and protects the intestinal epithelium. The review starts by setting up the biological context underpinning the need for experimental models to study gut bacteria-mucus interactions in the digestive environment. We provide an overview of the structure and function of intestinal mucus and mucins, their interactions with intestinal bacteria (including commensal, probiotics and pathogenic microorganisms) and their role in modulating health and disease states. We then describe the characteristics and potentials of experimental models currently available to study the mechanisms underpinning the interaction of mucus with gut microbes, including in vitro, ex vivo and in vivo models. We then discuss the limitations and challenges facing this field of research

Effectiveness and Acceptance of a Smartphone-Based Virtual Agent Screening for Alcohol and Tobacco Problems and Associated Risk Factors During COVID-19 Pandemic in the General Population

Background: During the current COVID-19 pandemic, alcohol, and tobacco are the most available substances for managing stress and can induce a risk of addiction. KANOPEE is a smartphone application available to the general population using an embodied conversational agent (ECA) to screen for experiences of problems with alcohol/tobacco use and to provide follow-up tools for brief intervention.Objectives: This study aimed to determine if the smartphone KANOPEE application could identify people at risk for alcohol and/or tobacco use disorders in the context of the current COVID-19 pandemic, to assess adherence to a 7-day follow-up use diary, and to evaluate trust and acceptance of the application.Methods: The conversational agent, named Jeanne, interviewed participants about perceived problems with the use of alcohol and tobacco since the pandemic and explored risk for tobacco and alcohol use disorder with the five-item Cigarette Dependence Scale (CDS-5) and “Cut Down, Annoyed, Guilty, Eye-opener” (CAGE) questionnaire and experience of craving for each substance. Descriptive, univariate, and multivariate analyses were performed to specify personalized associations with reporting a problem with alcohol/tobacco use; descriptive analysis reported the experience with the intervention and acceptance and trust in the application.Results: From April 22 to October 26, 2020, 1,588 French participants completed the KANOPEE interview, and 318 answered the acceptance and trust scales. Forty-two percent of tobacco users and 27% of alcohol users reported problem use since the pandemic. Positive screening with CDS-5 and CAGE and craving were associated with reported problem use (p < 0.0001). Lockdown period influenced alcohol (p < 0.0005) but not tobacco use (p > 0.05). Eighty-eight percent of users reported that KANOPEE was easy to use, and 82% found Jeanne to be trustworthy and credible.Conclusion: KANOPEE was able to screen for risk factors for substance use disorder (SUD) and was acceptable to users. Reporting craving and being at risk for SUD seem to be early markers to be identified. Alcohol problem use seems to be more reliant on contextual conditions such as confinement. This method is able to offer acceptable, brief, and early intervention with minimal delay for vulnerable people.Bordeaux Region Aquitaine Initiative for NeurosciencePhénotypage humain et réalité virtuell

The Identification of CELSR3 and Other Potential Cell Surface Targets in Neuroendocrine Prostate Cancer.

UNLABELLED Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.g., HMMR and CESLR3). We further showed that cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) knockdown results in reduced NEPC tumor cell proliferation and migration in vitro. We provide in vivo data including laser capture microdissection followed by RNA-seq data supporting a causal role of CELSR3 in the development and/or maintenance of the phenotype associated with NEPC. Finally, we provide initial data that suggests CELSR3 is a target for T-cell redirection therapeutics. Further work is now needed to fully evaluate the utility of targeting CELSR3 with T-cell redirection or other similar therapeutics as a potential new strategy for patients with NEPC. SIGNIFICANCE The development of effective treatment for patients with NEPC remains an unmet clinical need. We have identified specific surface proteins, including CELSR3, that may serve as novel biomarkers or therapeutic targets for NEPC

First description of in situ chlorophyll fluorescence signal within East Antarctic coastal polynyas during fall and winter

Antarctic coastal polynyas are persistent and recurrent regions of open water located between the coast and the drifting pack-ice. In spring, they are the first polar areas to be exposed to light, leading to the development of phytoplankton blooms, making polynyas potential ecological hotspots in sea-ice regions. Knowledge on polynya oceanography and ecology during winter is limited due to their inaccessibility. This study describes i) the first in situ chlorophyll fluorescence signal (a proxy for chlorophyll-a concentration and thus presence of phytoplankton) in polynyas between the end of summer and winter, ii) assesses whether the signal persists through time and iii) identifies its main oceanographic drivers. The dataset comprises 698 profiles of fluorescence, temperature and salinity recorded by southern elephant seals in 2011, 2019-2021 in the Cape-Darnley (CDP;67˚S-69˚E) and Shackleton (SP;66˚S-95˚E) polynyas between February and September. A significant fluorescence signal was observed until April in both polynyas. An additional signal occurring at 130m depth in August within CDP may result from in situ growth of phytoplankton due to potential adaptation to low irradiance or remnant chlorophyll-a that was advected into the polynya. The decrease and deepening of the fluorescence signal from February to August was accompanied by the deepening of the mixed layer depth and a cooling and salinification of the water column in both polynyas. Using Principal Component Analysis as an exploratory tool, we highlighted previously unsuspected drivers of the fluorescence signal within polynyas. CDP shows clear differences in biological and environmental conditions depending on topographic features with higher fluorescence in warmer and saltier waters on the shelf compared with the continental slope. In SP, near the ice-shelf, a significant fluorescence signal in April below the mixed layer (around 130m depth), was associated with fresher and warmer waters. We hypothesize that this signal could result from potential ice-shelf melting from warm water intrusions onto the shelf leading to iron supply necessary to fuel phytoplankton growth. This study supports that Antarctic coastal polynyas may have a key role for polar ecosystems as biologically active areas throughout the season within the sea-ice region despite inter and intra-polynya differences in environmental conditions