De novo mutations in CHD8 are strongly associated with autism spectrum disorder (ASD), however the basic biology of CHD8 remains poor understood. Here we report that Chd8 knockdown during cortical development results in defective neural progenitor proliferation and differentiation that ultimately manifests in abnormal neuronal morphology and behaviors in adult mice. Transcriptome analysis revealed that while Chd8 stimulates the transcription of cell cycle genes, it also precludes the induction of neural specific genes by regulating the expression of PRC2 complex components. Furthermore, knockdown of Chd8 disrupts the expression of key transducers of Wnt signaling, and enhancing Wnt signaling rescues the transcriptional and behavioral deficits caused by Chd8 knockdown. We propose that these roles of Chd8 and the dynamics of Chd8 expression during development help negotiate the fine balance between neural progenitor proliferation and differentiation. Together, these observations provide new insights into the neurodevelopmental role of Chd8.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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In response to the COVID-19 pandemic, institutions of higher education in almost every nation closed in the first half of 2020. University administrators are now facing decisions about how to safely return students, staff and faculty to campus. To provide a framework to evaluate various strategies, we developed a susceptible-exposed-infectious-recovered (SEIR) type of deterministic compartmental transmission model of SARS-CoV-2 among students, staff and faculty. Our goals were to support the immediate pandemic planning at our own university, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. We parameterized the model for our institution, Emory University, a medium-size private university in Atlanta, Georgia. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explore a range of screening and testing frequencies and perform a probabilistic sensitivity analysis of input parameters. We find that monthly and weekly screening can reduce cumulative incidence by 42% and 80% in students, respectively, while testing with a 2-, 4- and 7-day delay results in an 88%, 79% and 67% reduction in cumulative incidence in students over the semester, respectively. Similar reductions are observed among staff and faculty. A testing strategy requires far fewer diagnostic assays to be implemented than a screening assay. Our intervention model is conservative in that we assume a fairly high reproductive number that is not reduced through social distancing measures. We find that community-introduction of SARS-CoV-2 infection onto campus can be controlled with effective testing, isolation, contract tracing and quarantine, but that cases, hospitalization, and (in some scenarios) deaths may still occur. In addition to estimating health impacts, this model can help to predict the resource requirements in terms of diagnostic capacity and isolation/quarantine facilities associated with different strategies.

University administrators face decisions about how to safely return and maintain students, staff and faculty on campus throughout the 2020–21 school year. We developed a susceptible-exposed-infectious-recovered (SEIR) deterministic compartmental transmission model of SARS-CoV-2 among university students, staff, and faculty. Our goals were to inform planning at our own university, Emory University, a medium-sized university with around 15,000 students and 15,000 faculty and staff, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explored a range of screening and testing frequencies and performed a probabilistic sensitivity analysis. We found that among students, monthly and weekly screening can reduce cumulative incidence by 59% and 87%, respectively, while testing with a 2-, 4- and 7-day delay between onset of infectiousness and testing results in an 84%, 74% and 55% reduction in cumulative incidence. Smaller reductions were observed among staff and faculty. Community-introduction of SARS-CoV-2 onto campus may be controlled with testing, isolation, contract tracing and quarantine. Screening would need to be performed at least weekly to have substantial reductions beyond disease surveillance. This model can also inform resource requirements of diagnostic capacity and isolation/quarantine facilities associated with different strategies.

Background: Physical distancing measures aim to reduce person-to-person contact, a key driver of transmission of respiratory infections such as SARS-CoV-2. In response to unprecedented restrictions on human contact during the COVID-19 pandemic, a number of studies measured social contact patterns under the implementation of physical distancing measures. This rapid review aims to synthesize empirical data on the changing social contact patterns during the COVID-19 pandemic. Method: We conducted a systematic review using PubMed, Medline, Embase and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We descriptively compared the distribution of contacts observed during the pandemic to pre-COVID data across countries to explore changes in contact patterns during physical distancing measures. Results: We identified 12 studies that reported social contact patterns during the COVID-19 pandemic. The majority of studies (11/12) collected data during the initial mitigation period in the spring of 2020 marked by government-declared lockdowns and the most stringent physical distancing measures. Some studies collected additional data after relaxation of initial mitigation. Most study settings reported a mean of between 2-5 contacts per person per day, a substantial reduction compared to pre-COVID rates which ranged from 7-26 contacts per day in similar settings. This reduction was particularly pronounced for contacts outside of the home. Consequently, levels of assortative mixing by age substantially declined. After relaxation of initial mitigation, mean contact rates subsequently increased but did not return to pre-COVID levels. Increases in contacts post-relaxation were driven by working-age adults. Conclusion: Information on changes in contact patterns during physical distancing measures can guide more realistic representations of contact patterns in mathematical models for SARS-CoV-2 transmission.

We measured contact patterns using online diaries for 304 employees of 3 U.S. companies working remotely. The median number of daily contacts was 2 (IQR 1–4); majority were conversation (55 %), occurred at home (64 %) and lasted >4 h (38 %). These data are crucial for modeling outbreak control among the workforces.

C3 is a predatory strain of Gram-negative gliding bacteria that produces antifungal antibiotics by the polyketide synthetic pathway. Outer membrane vesicles (OMV) are formed as a stress response and can deliver virulence factors to host cells. The production of OMV by C3 and their role in antifungal activity are reported here. Vesicles in the range of 130 to 150 nm in diameter were discovered in the cell-free supernatants of C3 cultures. These OMV contain molecules characteristic of bacterial outer membranes, such as lipopolysaccharide and phospholipids. In addition, they contain chitinase activity and essentially all of the heat-stable antifungal activity in cell supernatants. We show here that C3 OMV can directly inhibit growth of the yeast as well as that of the filamentous fungus The activity is dependent on physical contact between OMV and the cells. Furthermore, fluorescent lipid labeling of C3 OMV demonstrated transfer of the membrane-associated probe to yeast cells, suggesting the existence of a mechanism of delivery for membrane-associated molecules. Mass spectrometric analysis of C3 OMV extracts indicates the presence of molecules with molecular weights identical to some of the previously identified antifungal products of C3. These data together suggest that OMV act as an important remote mobile component of predation by The data presented here suggest a newly discovered function of outer membrane vesicles (OMV) that are produced from the outer membrane of the bacterial species strain C3. We show that these OMV can be released from the surface of the cells to deliver antibiotics to target fungal organisms as a mechanism of killing or growth inhibition. Understanding the role of OMV in antibiotic delivery can generally lead to improved strategies for dealing with antibiotic-resistant organisms. These results also add to the evidence that some bacterially produced antibiotics can be discovered and purified using methods designed for isolation of nanoscale vesicles. Information on these systems can lead to better identification of active molecules or design of delivery vehicles for these molecules.

ObjectivesWe analysed data collected during programmatic screening activities conducted in 2017 to describe hepatitis C virus (HCV) seroprevalence in the general population and identify associated factors.DesignWe analysed data collected between June and September 2017. For both seroprevalence and viraemia, variations across demographic and geographic factors were assessed and multivariate regression models were fit to identify factors independently associated with each marker. Geospatial data were examined for visualisation.SettingHCV screening was organised within each of the 30 districts in Rwanda. One designated location in each district was selected as the screening site and screening took place for 1 week at each site.ParticipantsThis study included 124 223 male and female volunteers. Anti-HCV-positive individuals were followed up with HCV RNA viral load (VL) testing for infection confirmation.Main outcome measuresTwo markers were examined: the presence of HCV antibodies and HCV RNA VL.ResultsAmong 124 223 individuals screened, 11 003 (8.86%, 95% CIs: 8.70% to 9.02%) were positive for anti-HCV. Anti-HCV prevalence varied by age with the oldest age group (>55 year olds) having a prevalence of 16.46% (95% CIs: 16.14% to 16.80%) and the youngest age group (<25 year olds) having a prevalence of 2.20% (95% CIs: 1.93% to 2.50%) (crude OR=8.78). After adjustment for covariates, an association remained between anti-HCV prevalence and age (p<0.001), province (p<0.001) and socioeconomic status (p<0.001). Of the 3771 anti-HCV-positive individuals who had an available HCV RNA VL result, 2099 (55.66%, 95% CI: 54.06% to 57.25%) had a detectable HCV RNA VL. Age was also associated with HCV viraemia (p<0.001).ConclusionResults suggest that over 55% of individuals who screened positive for HCV-antibodies were chronically infected. Targeted screening for HCV among older individuals is recommended, given the association between age and infection. Further geographical hotspots of HCV infection can also inform targeted screening as Rwanda moves towards HCV elimination.