Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021

OBJECTIVE: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021. METHODS: We conducted a prospective cohort study of COVID-19 cases and close contacts among students and staff (n = 65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. The projected number of school-based transmission events among untested close contacts was extrapolated from the percentage of events detected among tested asymptomatic close contacts and summed with the number of detected events for a projected total. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy. RESULTS: From January-March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio = 1.00; 95% confidence interval: 0.97-1.03). DISCUSSION: School-based SARS-CoV-2 transmission was rare in 103 K-12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K-12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence

A diagnosis on torque reversals in 4U 1626-67

Several X-ray pulsars have been observed to experience torque reversals, which provide important observational clues to the interaction between the neutron star magnetic field and the accretion disk. We review the current models proposed for the torque reversals and discuss their viability based on the observations of the quasi-periodic oscillations (QPOs) in 4U 1626-67. Most of these models seem to be incompatible with the evolution of the QPO frequencies if they are interpreted in terms of the beat frequency model. We suggest that winds or outflows from the neutron star and the accretion disk may play an important role in accounting for the spin-down in disk-fed neutron stars.Comment: 7 pages, accepted for publication in A&

Ring closing reaction in diarylethene captured by femtosecond electron crystallography

The photoinduced ring-closing reaction in diarylethene, which serves as a model system for understanding reactive crossings through conical intersections, was directly observed with atomic resolution using femtosecond electron diffraction. Complementary ab initio calculations were also performed. Immediately following photoexcitation, subpicosecond structural changes associated with the formation of an open-ring excited-state intermediate were resolved. The key motion is the rotation of the thiophene rings, which significantly decreases the distance between the reactive carbon atoms prior to ring closing. Subsequently, on the few picosecond time scale, localized torsional motions of the carbon atoms lead to the formation of the closed-ring photoproduct. These direct observations of the molecular motions driving an organic chemical reaction were only made possible through the development of an ultrabright electron source to capture the atomic motions within the limited number of sampling frames and the low data acquisition rate dictated by the intrinsically poor thermal conductivity and limited photoreversibility of organic materials

High impact = high statistical standards? Not necessarily so.

What are the statistical practices of articles published in journals with a high impact factor? Are there differences compared with articles published in journals with a somewhat lower impact factor that have adopted editorial policies to reduce the impact of limitations of Null Hypothesis Significance Testing? To investigate these questions, the current study analyzed all articles related to psychological, neuropsychological and medical issues, published in 2011 in four journals with high impact factors: Science, Nature, The New England Journal of Medicine and The Lancet, and three journals with relatively lower impact factors: Neuropsychology, Journal of Experimental Psychology-Applied and the American Journal of Public Health. Results show that Null Hypothesis Significance Testing without any use of confidence intervals, effect size, prospective power and model estimation, is the prevalent statistical practice used in articles published in Nature, 89%, followed by articles published in Science, 42%. By contrast, in all other journals, both with high and lower impact factors, most articles report confidence intervals and/or effect size measures. We interpreted these differences as consequences of the editorial policies adopted by the journal editors, which are probably the most effective means to improve the statistical practices in journals with high or low impact factors

Assessing COVID-19 testing strategies in K-12 schools in underserved populations: Study protocol for a cluster-randomized trial

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Formation of Mobile Chromatin-Associated Nuclear Foci Containing HIV-1 Vpr and VPRBP Is Critical for the Induction of G2 Cell Cycle Arrest

HIV-1 Viral protein R (Vpr) induces a cell cycle arrest at the G2/M phase by activating the ATR DNA damage/stress checkpoint. Recently, we and several other groups showed that Vpr performs this activity by recruiting the DDB1-CUL4A (VPRBP) E3 ubiquitin ligase. While recruitment of this E3 ubiquitin ligase complex has been shown to be required for G2 arrest, the subcellular compartment where this complex forms and functionally acts is unknown. Herein, using immunofluorescence and confocal microscopy, we show that Vpr forms nuclear foci in several cell types including HeLa cells and primary CD4+ T-lymphocytes. These nuclear foci contain VPRBP and partially overlap with DNA repair foci components such as γ-H2AX, 53BP1 and RPA32. While treatment with the non-specific ATR inhibitor caffeine or depletion of VPRBP by siRNA did not inhibit formation of Vpr nuclear foci, mutations in the C-terminal domain of Vpr and cytoplasmic sequestration of Vpr by overexpression of Gag-Pol resulted in impaired formation of these nuclear structures and defective G2 arrest. Consistently, we observed that G2 arrest-competent sooty mangabey Vpr could form these foci but not its G2 arrest-defective paralog Vpx, suggesting that formation of Vpr nuclear foci represents a critical early event in the induction of G2 arrest. Indeed, we found that Vpr could associate to chromatin via its C-terminal domain and that it could form a complex with VPRBP on chromatin. Finally, analysis of Vpr nuclear foci by time-lapse microscopy showed that they were highly mobile and stable structures. Overall, our results suggest that Vpr recruits the DDB1-CUL4A (VPRBP) E3 ligase to these nuclear foci and uses these mobile structures to target a chromatin-bound cellular substrate for ubiquitination in order to induce DNA damage/replication stress, ultimately leading to ATR activation and G2 cell cycle arrest

Innate Signaling in Otitis Media: Pathogenesis and Recovery

Otitis media (OM) is the most prevalent childhood disease in developed countries. Involvement of innate immunity mediated by Toll-like receptors (TLRs) in OM has been implicated primarily in cell lines and by association studies of innate immune gene polymorphisms with OM prevalence. However, the precise role of innate immunity in OM is incompletely understood. We review recent research that has advanced our understanding of how innate immunity in the middle ear is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and production of proinflammatory cytokines. TLR genes and signaling molecules are upregulated in OM in a murine model. Deletion of several key innate immune genes results in persistent OM in mice, coupled with an inability to clear bacterial infection from the middle ear. It is concluded that an intact innate immune signaling system is critical to recovery from bacterial OM

Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children