Plasma cells (PCs) constitute a significant fraction of colonic mucosal cells and contribute to inflammatory infiltrates in ulcerative colitis (UC). While gut PCs secrete bacteria-targeting IgA ...antibodies, their role in UC pathogenesis is unknown. We performed single-cell V(D)J- and RNA-seq on sorted B cells from the colon of healthy individuals and patients with UC. A large fraction of B cell clones is shared between different colon regions, but inflammation in UC broadly disrupts this landscape, causing transcriptomic changes characterized by an increase in the unfolded protein response (UPR) and antigen presentation genes, clonal expansion, and isotype skewing from IgA1 and IgA2 to IgG1. We also directly expressed and assessed the specificity of 152 mAbs from expanded PC clones. These mAbs show low polyreactivity and autoreactivity and instead target both shared bacterial antigens and specific bacterial strains. Altogether, our results characterize the microbiome-specific colon PC response and how its disruption might contribute to inflammation in UC.
What is already known about this topic? COVID-19 vaccination began in the United States in December 2020, and adults aged ≥65 years were prioritized in early phases. What is added by this report? By ...May 1, 2021, 82%, 63%, and 42% of adults aged ≥65, 50–64, and 18–49 years, respectively, had received ≥1 vaccine dose. From November 29–December 12, 2020 to April 18–May 1, 2021, the rate ratios of COVID-19 incidence, emergency department visits, hospital admissions, and deaths among adults aged ≥65 years (≥70 years for hospitalizations) to adults aged 18–49 years declined 40%, 59%, 65%, and 66%, respectively. What are the implications for public health practice? The greater decline in COVID-19 morbidity and mortality in older adults, the age group with the highest vaccination rates, demonstrates the potential impact of increasing population-level vaccination coverage.
Purpose
Despite decades of studies on high-involvement human resource management (HRM) systems, questions remain of whether high-involvement HRM systems can increase the commitment of women. This ...study aims to contribute to the growing body of research on the cross-level effect of HRM systems and practices on employee affective commitment by considering the moderating role of gender.
Design/methodology/approach
Integrating social exchange theory with gender role theory, this paper proposes that gender responses to HRM practices can be different. The hypotheses were tested using data from 104 small- and medium-sized retail enterprises and 6,320 employees from Spain.
Findings
The findings generally support the study’s hypotheses, with women’s affective commitment responding more strongly and positively to employees’ aggregated perceptions of a shop-level high-involvement HRM system. The findings imply that a high-involvement HRM system can promote the affective commitment of women.
Originality/value
This study investigates the impact of both an overall HRM system and function-specific HRM sub-systems (e.g. training, information, participation and autonomy). By showing that women can be more positively affected by high-involvement HRM systems, this paper suggests that high-involvement HRM systems can be used to encourage the involvement and participation of women.
The Semanticscience Integrated Ontology (SIO) is an ontology to facilitate biomedical knowledge discovery. SIO features a simple upper level comprised of essential types and relations for the rich ...description of arbitrary (real, hypothesized, virtual, fictional) objects, processes and their attributes. SIO specifies simple design patterns to describe and associate qualities, capabilities, functions, quantities, and informational entities including textual, geometrical, and mathematical entities, and provides specific extensions in the domains of chemistry, biology, biochemistry, and bioinformatics. SIO provides an ontological foundation for the Bio2RDF linked data for the life sciences project and is used for semantic integration and discovery for SADI-based semantic web services. SIO is freely available to all users under a creative commons by attribution license. See website for further information: http://sio.semanticscience.org.
When the U.S. COVID-19 public health emergency declaration expires on May 11, 2023, national reporting of certain categories of COVID-19 public health surveillance data will be transitioned to other ...data sources or will be discontinued; COVID-19 hospitalization data will be the only data source available at the county level (1). In anticipation of the transition, national COVID-19 surveillance data sources and indicators were evaluated for purposes of ongoing monitoring. The timeliness and correlations among surveillance indicators were analyzed to assess the usefulness of COVID-19-associated hospital admission rates as a primary indicator for monitoring COVID-19 trends, as well as the suitability of other replacement data sources. During April 2022-March 2023, COVID-19 hospital admission rates from the National Healthcare Safety Network (NHSN)
lagged 1 day behind case rates and 4 days behind percentages of positive test results and COVID-19 emergency department (ED) visits from the National Syndromic Surveillance Program (NSSP). In the same analysis, National Vital Statistics System (NVSS) trends in the percentage of deaths that were COVID-19-associated, which is tracked by date of death rather than by report date, were observable 13 days earlier than those from aggregate death count data, which will be discontinued (1). During October 2020-March 2023, strong correlations were observed between NVSS and aggregate death data (0.78) and between the percentage of positive SARS-CoV-2 test results from the National Respiratory and Enteric Viruses Surveillance System (NREVSS) and COVID-19 electronic laboratory reporting (CELR) (0.79), which will also be discontinued (1). Weekly COVID-19 Community Levels (CCLs) will be replaced with levels of COVID-19 hospital admission rates (low, medium, or high) which demonstrated >99% concordance by county during February 2022-March 2023. COVID-19-associated hospital admission levels are a suitable primary metric for monitoring COVID-19 trends, the percentage of COVID-19 deaths is a timely disease severity indicator, and the percentages of positive SARS-CoV-2 test results from NREVSS and ED visits serve as early indicators for COVID-19 monitoring. Collectively, these surveillance data sources and indicators can support monitoring of the impact of COVID-19 and related prevention and control strategies as ongoing public health priorities.
On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a ...novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4).
The higher prevalence of metopic and sagittal suture synostosis in male infants suggests a role for androgens in early craniofacial development. These experiments characterize the influence of ...androgen stimulation on growth and differentiation of fetal dural and calvarial bone cells and on cranial suture fusion.
Primary murine fetal (E18) dural cells and calvarial osteoblasts were isolated and cultured. Cells were treated for 48 hours with 5alpha-dihydrotestosterone (0 to 1000 nM). Cell proliferation was examined by nonradioactive proliferation assay; mRNA expression of alkaline phosphatase, transforming growth factor (TGF)-beta1, and the bone matrix proteins osteopontin, osteocalcin, and type 1 collagen was determined by reverse-transcriptase polymerase chain reaction. In separate experiments, intact fetal calvariae were grown in tissue culture with 10 nM 5alpha-dihydrotestosterone for 7 and 14 days and then examined histologically.
Androgen stimulation at 5 nM increased proliferation of fetal dural cells by 46.0 percent and of fetal calvarial osteoblasts by 20.5 percent. Dural expression of osteopontin, osteocalcin, and type 1 collagen was enhanced by 5alpha-dihydrotestosterone, as was that of TGF-beta1 and alkaline phosphatase. Androgen stimulation increased calvarial osteoblast expression of alkaline phosphatase and TGF-beta1 but induced little change in expression of osteocalcin, osteopontin, and type 1 collagen. In tissue culture, 5alpha-dihydrotestosterone stimulated osteoid formation and fusion of sagittal sutures.
Androgen stimulation of dural cells and osteoblasts isolated from fetal calvaria promotes cell proliferation and osteoblastic differentiation and can induce cranial suture fusion. These results suggest that sex steroid hormone signaling may stimulate sutural osteogenesis by means of osteodifferentiation of dural cells, thus explaining the male prevalence of nonsyndromic craniosynostosis.
Previously, we reported the phosphorylation of a 36 kDa protein, p36, in crude membranes from the amoeba Dictyostelium discoideum (Anschutz, A.L., Howlett, A. and Klein, C. (1989) Proc. Natl. Acad. ...Sci. USA 86, 3665-3668). Here, we report the purification and identification of p36. The protein was purified approximately 35-40-fold with a yield of 8-10%. This material was then separated on 10% SDS-polyacrylamide gels and the band corresponding to p36 was isolated. Partial peptide sequencing of this band revealed p36 to be homologous to the alpha-subunit of succinyl-CoA synthetase. This identification of the protein was supported by the results of phosphorylation studies which examined the effects of substrates of succinyl-CoA synthetase on p36 phosphorylation. In crude sample preparations, p36 could be phosphorylated by both ATP or GTP and in either case, its phosphorylation was stimulated by low concentrations of GDP. Partially purified p36 retained its ability to be phosphorylated with GTP while exhibiting little or no phosphorylation with ATP. GDP still enhanced the rate of p36 phosphorylation with GTP. Therefore, the stimulation of p36 phosphorylation by GDP is not due to substrate conversion and is best explained by a regulatory mechanism.
We have examined the phosphorylation of the cyclic adenosine 3':5' monophosphate (cAMP) cell surface chemotactic receptor and a 36 kDa membrane-associated protein (p36) in Dictyostelium discoideum. ...The activity of CAR-kinase, the enzyme responsible for the phosphorylation of the cAMP receptor, was studied in plasma membrane preparations. It was found that, as in intact cells, the receptor was rapidly phosphorylated in membranes incubated with gamma 32P adenosine triphosphate (ATP) but only in the presence of cAMP. This phosphorylation was not observed in membranes prepared from cells which did not display significant cAMP binding activity. cAMP could induce receptor phosphorylation at low concentrations, while cyclic guanosine 3':5' monophosphate (cGMP) could elicit receptor phosphorylation only at high concentrations. Neither ConA, Ca2+, or guanine nucleotides had an effect on CAR-kinase. It was also observed that 2-deoxy cAMP but not dibutyryl cAMP induced receptor phosphorylation. The data suggest that the ligand occupied form of the cAMP receptor is required for CAR-kinase activity. Although the receptor is rapidly dephosphorylated in vivo, we were unable to observe its dephosphorylation in vitro. In contrast, p36 was rapidly dephosphorylated. Also, unlike the cAMP receptor, the phosphorylation of p36 was found to be regulated by the addition of guanine nucleotides. Guanosine diphosphate (GDP) enhanced the phosphorylation while guanosine triphosphate (GTP) decreased the radiolabeling of p36 indicating that GTP can compete with ATP for the nucleotide triphosphate binding site of p36 kinase. Thus was verified using radiolabeled GTP as the phosphate donor. Competition experiments with GTP gamma S, ATP, GTP, CTP, and uridine triphosphate (UTP) indicated that the phosphate donor site of p36 kinase is relatively non-specific.
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