Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses.

Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known.

Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics.

Pathogen-driven CRISPR screens identify TREX1 as a regulator of DNA self-sensing during influenza virus infection.

Host:pathogen interactions dictate the outcome of infection, yet the limitations of current approaches leave large regions of this interface unexplored. Here, we develop a novel fitness-based screen that queries factors important during the middle to late stages of infection. This is achieved by engineering influenza virus to direct the screen by programming dCas9 to modulate host gene expression.

Sleep and Infantry Battle Drill Performance in Special Operations Soldiers.

Although multiple studies have documented the impact of insufficient sleep on soldier performance, most studies have done so using artificial measures of performance (e.g., tablet or simulator tests).

Human Cytomegalovirus UL138 Protein Inhibits the STING Pathway and Reduces Interferon Beta mRNA Accumulation during Lytic and Latent Infections.

The cGAS/STING/TBK1 (cyclic guanine monophosphate-AMP synthase/stimulator of interferon genes/Tank-binding kinase 1) innate immunity pathway is activated during human cytomegalovirus (HCMV) productive (lytic) replication in fully differentiated cells and during latency within incompletely differentiated myeloid cells. While multiple lytic-phase HCMV proteins neutralize steps along this pathway, none of them are expressed during latency. Here, we show that the latency-associated protein UL138 inhibits the cGAS/STING/TBK1 innate immunity pathway during transfections and infections, in fully differentiated cells and incompletely differentiated myeloid cells, and with loss of function and restoration of function approaches.

Genetic ancestry effects on the response to viral infection are pervasive but cell type specific.

Humans differ in their susceptibility to infectious disease, partly owing to variation in the immune response after infection. We used single-cell RNA sequencing to quantify variation in the response to influenza infection in peripheral blood mononuclear cells from European- and African-ancestry males. Genetic ancestry effects are common but highly cell type specific.

Mice with diverse microbial exposure histories as a model for preclinical vaccine testing.

Laboratory mice comprise an expeditious model for preclinical vaccine testing; however, vaccine immunogenicity in these models often inadequately translates to humans. Reconstituting physiologic microbial experience to specific pathogen-free (SPF) mice induces durable immunological changes that better recapitulate human immunity. We examined whether mice with diverse microbial experience better model human responses post vaccination.

Physical sleeping environment is related to insomnia risk and measures of readiness in US army special operations soldiers.

Background: US military service members have characteristically poor sleep, even when '' or at one's home base. The physical sleeping environment, which is often poor in military-provided housing or barracks, may contribute to poor sleep quality in soldiers. The current study aimed to assess whether the sleeping environment in garrison is related to sleep quality, insomnia risk and military readiness.

Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants.

Nucleocapsid vaccine elicits spike-independent SARS-CoV-2 protective immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing antibodies target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants.

Sleep and high-risk behavior in military service members: a mega-analysis of four diverse U.S. Army units.

Experimental sleep restriction and deprivation lead to risky decision-making. Further, in naturalistic settings, short sleep duration and poor sleep quality have been linked to real-world high-risk behaviors (HRB), such as reckless driving or substance use. Military populations, in general, tend to sleep less and have poorer sleep quality than nonmilitary populations due to a number of occupational, cultural, and psychosocial factors (e.

Competing mechanisms of plasticity impair compensatory responses to repetitive apnoea.

Key Points: Intermittent reductions in respiratory neural activity, a characteristic of many ventilatory disorders, leads to inadequate ventilation and arterial hypoxia. Both intermittent reductions in respiratory neural activity and intermittent hypoxia trigger compensatory enhancements in inspiratory output when experienced separately, forms of plasticity called inactivity-induced inspiratory motor facilitation (iMF) and long-term facilitation (LTF), respectively. Reductions in respiratory neural activity that lead to moderate, but not mild, arterial hypoxia occludes plasticity expression, indicating that concurrent induction of iMF and LTF impairs plasticity through cross-talk inhibition of their respective signalling pathways.

Early exposure to anesthesia and learning disabilities in a population-based birth cohort.

Background: Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. The authors studied association between anesthetic exposure before age 4 yr and the development of reading, written language, and math learning disabilities (LD).

Methods: This was a population-based, retrospective birth cohort study.

The evolution of public review and oversight mechanisms in human gene transfer research: joint roles of the FDA and NIH.

The federal government is critically examining its responsibilities and opportunities for bringing the new field of gene therapy to fruition and for assuring public confidence in this new area of biomedicine. The evolving mechanisms for review and regulation in human gene transfer studies in the United States are being enhanced by increasingly effective interactions between the Food and Drug Administration and the National Institutes of Health.

Isolation of the CD7 gene from the DNA of transfected L cells.

Using DNA from L cells which expressed high levels of the CD7 (Leu-9 or HuLy-m2) antigen obtained after two cycles of transfection, a genomic library was constructed in the lambda phage Charon 4A. Recombinant clones containing the gene coding for this antigen were identified by first screening the library with both the HSV-tk gene and a probe detecting the human repetitive (Alu) sequences. DNA from 10 tk+ and 12 Alu+ recombinant clones was used to transfect L cells which were analyzed for the cell-surface expression of CD7 either early (48-72 h posttransfection) or later when hypoxanthine aminopterin thymidine-resistant colonies were obtained.

Identification of two forms of the Ly-6.2 antigen showing differential expression.

A monoclonal antibody to the Ly-6.2 specificity, defined by strain and tissue distribution, was used to identify the cellular antigens of lymphocytes and tumor cell lines. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immune precipitates demonstrated that the Ly-6.

Genetic and amber fragment maps of genes 46 and 47 of bacteriophage T4D.

We constructed genetic recombinational maps of genes 46 and 47 by using five amber mutants in gene 46, nine amber mutants in gene 47, and two-factor crosses. Two different amber fragments in gene 46 and three different amber fragments in gene 47 were detected on polyacrylamide slab gels in the presence of sodium dodecyl sulfate. The genetic maps agreed with the amber fragment maps; taken together, the data oriented all of the sites in both genes with respect to each other.

Membrane-associated DNase activity controlled by genes 46 and 47 of bacteriophage T4D and elevated DNase activity associated with the T4 das mutation.

Lethal, amber mutations in T4 genes 46 and 47 cause incomplete degradation of host DNA, premature arrest of phage DNA synthesis, accumulation of abnormal DNA replication intermediates, and defective recombination. These phenotypes can be explained by the hypothesis that genes 46 and 47 control a DNA exonuclease, but in vitro demonstration of such a nuclease has not yet been reported. Membrane and supernatant fractions from 46- and 47- mutant-infected and 46+ 47+ control-infected cells were assayed for the presence of the protein products of these genes (i.