Helping the helpers: Tending to Kansas educators’ social-emotional needs and self-care during a pandemic

On a typical day, pre-COVID 19, educators are pulled in many directions, making hundreds, if not thousands, of quick decisions. Today those dynamics are heightened with varied and additional competing needs. However, what has not changed is the essential role of an educator. Caring for students in a time of such uncertainty seems critical. However, while there is serious and necessary demand for caring for the students and families, one population that is gravely being overlooked are the helpers. The educators. Less emphasis is being placed on the wellness and self-care of those who are offering those needed social-emotional supports. For a myriad of reasons, it is clear that emphasis must be placed on tending to the needs of Kansas educators’ well-being. In an effort to maintain educator passion and performance, messages around self-care, building social-emotionally competent classrooms and school climates are addressed

CSF1R mosaicism in a family with hereditary diffuse leukoencephalopathy with spheroids

Mutations in the colony stimulating factor 1 receptor

Historically unprecedented Northern Gulf of Mexico hurricane activity from 650 to 1250 CE

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Rodysill, J. R., Donnelly, J. P., Sullivan, R., Lane, P. D., Toomey, M., Woodruff, J. D., Hawkes, A. D., MacDonald, D., d'Entremont, N., McKeon, K., Wallace, E., & van Hengstum, P. J. Historically unprecedented Northern Gulf of Mexico hurricane activity from 650 to 1250 CE. Scientific Reports, 10(1), (2020): 19092. doi:10.1038/s41598-020-75874-0.Hurricane Michael (2018) was the first Category 5 storm on record to make landfall on the Florida panhandle since at least 1851 CE (Common Era), and it resulted in the loss of 59 lives and $25 billion in damages across the southeastern U.S. This event placed a spotlight on recent intense (exceeding Category 4 or 5 on the Saffir-Simpson Hurricane Wind Scale) hurricane landfalls, prompting questions about the natural range in variability of hurricane activity that the instrumental record is too short to address. Of particular interest is determining whether the frequency of recent intense hurricane landfalls in the northern Gulf of Mexico (GOM) is within or outside the natural range of intense hurricane activity prior to 1851 CE. In this study, we identify intense hurricane landfalls in northwest Florida during the past 2000 years based on coarse anomaly event detection from two coastal lacustrine sediment archives. We identified a historically unprecedented period of heightened storm activity common to four Florida panhandle localities from 650 to 1250 CE and a shift to a relatively quiescent storm climate in the GOM spanning the past six centuries. Our study provides long-term context for events like Hurricane Michael and suggests that the observational period 1851 CE to present may underrepresent the natural range in landfalling hurricane activity.Funding for this project was provided by the Strategic Environmental Research and Development Program (SERDP) grant and NSF awards 0903020, 1902463, and 1854980 awarded to Jeffrey Donnelly, and the USGS Land Change Science Program

Evaluation and extension of the two-site, two-step model for binding and activation of the chemokine receptor CCR1

© 2019 Sanchez et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Interactions between secreted immune proteins called chemokines and their cognate G protein– coupled receptors regulate the trafficking of leukocytes in inflammatory responses. The two-site, two-step model describes these interactions. It involves initial binding of the chemokine N-loop/3 region to the receptor’s N-terminal region and subsequent insertion of the chemokine N-terminal region into the transmembrane helical bundle of the receptor concurrent with receptor activation. Here, we test aspects of this model with C-C motif chemokine receptor 1 (CCR1) and several chemokine ligands. First, we compared the chemokine-binding affinities of CCR1 with those of peptides corresponding to the CCR1 N-terminal region. Relatively low affinities of the peptides and poor correlations between CCR1 and peptide affinities indicated that other regions of the receptor may contribute to binding affinity. Second, we evaluated the contributions of the two CCR1-interacting regions of the cognate chemokine ligand CCL7 (formerly monocyte chemoattractant protein-3 (MCP-3)) using chimeras between CCL7 and the non-cognate ligand CCL2 (formerly MCP-1). The results revealed that the chemokine N-terminal region contributes significantly to binding affinity but that differences in binding affinity do not completely account for differences in receptor activation. On the basis of these observations, we propose an elaboration of the two-site, two-step model—the “three-step” model—in which initial interactions of the first site result in low-affinity, nonspecific binding; rate-limiting engagement of the second site enables high-affinity, specific binding; and subsequent conformational rearrangement gives rise to receptor activation

GeneMatch: A novel recruitment registry using at‐home APOE genotyping to enhance referrals to Alzheimer’s prevention studies

IntroductionRecruitment for Alzheimer’s disease (AD) prevention research studies is challenging because of lack of awareness among cognitively healthy adults coupled with the high screen fail rate due to participants not having a genetic risk factor or biomarker evidence of the disease. Participant recruitment registries offer one solution for efficiently and effectively identifying, characterizing, and connecting potential eligible volunteers to studies.MethodsIndividuals aged 55‐75 years who live in the United States and self‐report not having a diagnosis of cognitive impairment such as MCI or dementia are eligible to join GeneMatch. Participants enroll online and are provided a cheek swab kit for DNA extraction and apolipoprotein E (APOE) genotyping. Participants are not told their APOE results, although the results may be used in part to help match participants to AD prevention studies.ResultsAs of August 2018, 75,351 participants had joined GeneMatch. Nearly 30% of participants have one APOE4 allele, and approximately 3% have two APOE4 alleles. The percentages of APOE4 heterozygotes and homozygotes are inversely associated with age (P < .001).DiscussionGeneMatch, the first trial‐independent research enrollment program designed to recruit and refer cognitively healthy adults to AD prevention studies based in part on APOE test results, provides a novel mechanism to accelerate prescreening and enrollment for AD prevention trials.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152681/1/alzjjalz201812007.pd

The Value Proposition of the Global Health Security Index

Infectious disease outbreaks pose major threats to human health and security. Countries with robust capacities for preventing, detecting and responding to outbreaks can avert many of the social, political, economic and health system costs of such crises. The Global Health Security Index (GHS Index)—the first comprehensive assessment and benchmarking of health security and related capabilities across 195 countries—recently found that no country is sufficiently prepared for epidemics or pandemics. The GHS Index can help health security stakeholders identify areas of weakness, as well as opportunities to collaborate across sectors, collectively strengthen health systems and achieve shared public health goals. Some scholars have recently offered constructive critiques of the GHS Index’s approach to scoring and ranking countries; its weighting of select indicators; its emphasis on transparency; its focus on biosecurity and biosafety capacities; and divergence between select country scores and corresponding COVID-19-associated caseloads, morbidity, and mortality. Here, we (1) describe the practical value of the GHS Index; (2) present potential use cases to help policymakers and practitioners maximise the utility of the tool; (3) discuss the importance of scoring and ranking; (4) describe the robust methodology underpinning country scores and ranks; (5) highlight the GHS Index’s emphasis on transparency and (6) articulate caveats for users wishing to use GHS Index data in health security research, policymaking and practice

Mutations in the Satellite Cell Gene MEGF10 Cause a Recessive Congenital Myopathy with Minicores

We ascertained a nuclear family in which three of four siblings were affected with an unclassified autosomal recessive myopathy characterized by severe weakness, respiratory impairment, scoliosis, joint contractures, and an unusual combination of dystrophic and myopathic features on muscle biopsy. Whole genome sequence from one affected subject was filtered using linkage data and variant databases. A single gene, MEGF10, contained nonsynonymous mutations that co-segregated with the phenotype. Affected subjects were compound heterozygous for missense mutations c.976T > C (p.C326R) and c.2320T > C (p.C774R). Screening the MEGF10 open reading frame in 190 patients with genetically unexplained myopathies revealed a heterozygous mutation, c.211C > T (p.R71W), in one additional subject with a similar clinical and histological presentation as the discovery family. All three mutations were absent from at least 645 genotyped unaffected control subjects. MEGF10 contains 17 atypical epidermal growth factor-like domains, each of which contains eight cysteine residues that likely form disulfide bonds. Both the p.C326R and p.C774R mutations alter one of these residues, which are completely conserved in vertebrates. Previous work showed that murine Megf10 is required for preserving the undifferentiated, proliferative potential of satellite cells, myogenic precursors that regenerate skeletal muscle in response to injury or disease. Here, knockdown of megf10 in zebrafish by four different morpholinos resulted in abnormal phenotypes including unhatched eggs, curved tails, impaired motility, and disorganized muscle tissue, corroborating the pathogenicity of the human mutations. Our data establish the importance of MEGF10 in human skeletal muscle and suggest satellite cell dysfunction as a novel myopathic mechanism