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Eriksen Buchanan posted an update 6 months ago
IMPORTANCE When facing a viral infection, the organism has to put in place a number of defense mechanisms in order to clear the pathogen from the cell. At the early phase of this preparation for fighting against the invader, the innate immune response is triggered by the sensing of danger signals. Among those molecular cues, double-stranded RNA (dsRNA) is a very potent inducer of different reactions at the cellular level that can ultimately lead to cell death. Using a genome-wide screening approach, we set to identify genes involved in dsRNA entry, sensing, and apoptosis induction in human cells. This allowed us to determine that the heparan sulfate pathway and the conserved oligomeric Golgi complex are key determinants allowing entry of both dsRNA and viral nucleic acid leading to cell death.Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. click here High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14+ CD16+ monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocive responses, which already begin to decline a few months after the resolution of symptoms.After the first case of coronavirus disease 2019 (COVID-19) in Japan on 15 January 2020, multiple nationwide COVID-19 clusters were identified by the end of February. The Japanese government focused on mitigating the emerging COVID-19 clusters by conducting active nationwide epidemiological surveillance. However, an increasing number of cases continued to appear until early April 2020, many with unclear infection routes and no recent history of travel outside Japan. We aimed to evaluate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from the COVID-19 cases that appeared until early April 2020 and to characterize their genealogical networks in order to demonstrate possible routes of spread in Japan. Nasopharyngeal specimens were collected from patients, and reverse transcription-quantitative PCR tests for SARS-CoV-2 were performed. Positive RNA samples were subjected to whole-genome sequencing, and a haplotype network analysis was performed. Some of the primary clusters idententered Japan and contribute to increased knowledge of SARS-CoV-2 in Asia and its association with implemented stay-at-home/shelter-in-place/self-restraint/lockdown measures. This study suggested that it is necessary to formulate a more efficient containment strategy using real-time genome surveillance to support epidemiological field investigations in order to highlight potential infection linkages and mitigate the next wave of COVID-19 in Japan.Pluripotent stem-cell-derived human intestinal organoids (HIOs) are three-dimensional, multicellular structures that model a naive intestinal epithelium in an in vitro system. Several published reports have investigated the use of HIOs to study host-microbe interactions. We recently demonstrated that microinjection of the nonpathogenic Escherichia coli strain ECOR2 into HIOs induced morphological and functional maturation of the HIO epithelium, including increased secretion of mucins and cationic antimicrobial peptides. In the current work, we use ECOR2 as a biological probe to further characterize the environment present in the HIO lumen. We generated an isogenic mutant in the general stress response sigma factor RpoS and employed this mutant to compare challenges faced by a bacterium during colonization of the HIO lumen relative to the germ-free mouse intestine. We demonstrate that the loss of RpoS significantly decreases the ability of ECOR2 to colonize HIOs, although it does not prevent colonization of germ-free mice. These results indicate that the HIO lumen is a more restrictive environment to E. coli than the germ-free mouse intestine, thus increasing our understanding of the HIO model system as it pertains to studying the establishment of intestinal host-microbe symbioses.IMPORTANCE Technological advancements have driven and will continue to drive the adoption of organotypic systems for investigating host-microbe interactions within the human intestinal ecosystem. Using E. coli deficient in the RpoS-mediated general stress response, we demonstrate that the type or severity of microbial stressors within the HIO lumen is more restrictive than those of the in vivo environment of the germ-free mouse gut. This study provides important insight into the nature of the HIO microenvironment from a microbiological standpoint.
This study examined the impact of a San Francisco City and County ban on all flavoured tobacco products, including menthol cigarettes, among clients in residential substance use disorder (SUD) treatment.
We conducted cross-sectional surveys of clients at two residential SUD programmes before the County began enforcing the ban (n=160) and twice after enforcement began (n=102, n=120). The samples were compared on demographic characteristics, smoking status, smoking behaviours and the proportion reporting menthol as their usual cigarette. Menthol smokers were asked whether they smoked only menthol cigarettes, mostly menthol, both menthol and non-menthol or mostly non-menthol. Post-ban samples were asked about awareness of the ban and access to menthol cigarettes.
In multivariate analyses, we found no evidence that the ban was associated with decreased number of cigarettes per day or increased readiness to quit among current smokers. However, odds were lower post-ban for reporting menthol as the usual cigarette (OR=0.
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