Flagellin outer domain dimerization modulates motility in pathogenic and soil bacteria from viscous environments.

Flagellar filaments function as the propellers of the bacterial flagellum and their supercoiling is key to motility. The outer domains on the surface of the filament are non-critical for motility in many bacteria and their structures and functions are not conserved. Here, we show the atomic cryo-electron microscopy structures for flagellar filaments from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. coli O127:H6, Achromobacter, and Sinorhizobium meliloti, where the outer domains dimerize or tetramerize to form either a sheath or a screw-like surface. These dimers are formed by 180° rotations of half of the outer domains. The outer domain sheath (ODS) plays a role in bacterial motility by stabilizing an intermediate waveform and prolonging the tumbling of E. coli cells. Bacteria with these ODS and screw-like flagellar filaments are commonly found in soil and human intestinal environments of relatively high viscosity suggesting a role for the dimerization in these environments

Grassy–herbaceous land moderates regional climate effects on honey bee colonies in the Northcentral US

The lack of seasonally sustained floral resources (i.e. pollen and nectar) is considered a primary global threat to pollinator health. However, the ability to predict the abundance of flowering resources for pollinators based upon climate, weather, and land cover is difficult due to insufficient monitoring over adequate spatial and temporal scales. Here we use spatiotemporally distributed honey bee hive scales that continuously measure hive weights as a standardized method to assess nectar intake. We analyze late summer colony weight gain as the response variable in a random forest regression model to determine the importance of climate, weather, and land cover on honey bee colony productivity. Our random forest model predicted resource acquisition by honey bee colonies with 71% accuracy, highlighting the detrimental effects of warm, wet regions in the Northcentral United States on nectar intake, as well as the detrimental effect of years with high growing degree day accumulation. Our model also predicted that grassy–herbaceous natural land had a positive effect on the summer nectar flow and that large areas of natural grassy–herbaceous land around apiaries can moderate the detrimental effects of warm, wet climates. These patterns characterize multi-scale ecological processes that constrain the quantity and quality of pollinator nutritional resources. That is, broad climate conditions constrain regional floral communities, while land use and weather act to further modify the quantity and quality of pollinator nutritional resources. Observing such broad-scale trends demonstrates the potential for utilizing hive scales to monitor the effects of climate change on landscape-level floral resources for pollinators. The interaction of climate and land use also present an opportunity to manage for climate-resilient landscapes that support pollinators through abundant floral resources under climate change

Characterizing the weight-glycemia phenotypes of type 1 diabetes in youth and young adulthood

Introduction Individuals with type 1 diabetes (T1D) present with diverse body weight status and degrees of glycemic control, which may warrant different treatment approaches. We sought to identify subgroups sharing phenotypes based on both weight and glycemia and compare characteristics across subgroups. Research design and methods Participants: with T1D in the SEARCH study cohort (n=1817, 6.0-30.4 years) were seen at a follow-up visit >5 years after diagnosis. Hierarchical agglomerative clustering was used to group participants based on five measures summarizing the joint distribution of body mass index z-score (BMIz) and hemoglobin A1c (HbA1c) which were estimated by reinforcement learning tree predictions from 28 covariates. Interpretation of cluster weight status and glycemic control was based on mean BMIz and HbA1c, respectively. Results: The sample was 49.5% female and 55.5% non-Hispanic white (NHW); mean±SD age=17.6±4.5 years, T1D duration=7.8±1.9 years, BMIz=0.61±0.94, and HbA1c=76±21 mmol/mol (9.1±1.9)%. Six weight-glycemia clusters were identified, including four normal weight, one overweight, and one subgroup with obesity. No cluster had a mean HbA1c <58 mmol/mol (7.5%). Cluster 1 (34.0%) was normal weight with the lowest HbA1c and comprised 85% NHW participants with the highest socioeconomic position, insulin pump use, dietary quality, and physical activity. Subgroups with very poor glycemic control (ie, ≥108 mmol/mol (≥12.0%); cluster 4, 4.4%, and cluster 5, 7.5%) and obesity (cluster 6, 15.4%) had a lower proportion of NHW youth, lower socioeconomic position, and reported decreased pump use and poorer health behaviors (overall p<0.01). The overweight subgroup with very poor glycemic control (cluster 5) showed the highest lipids and blood pressure (p<0.01). Conclusions: There are distinct subgroups of youth and young adults with T1D that share weight-glycemia phenotypes. Subgroups may benefit from tailored interventions addressing differences in clinical care, health behaviors, and underlying health inequity. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Antigen-Presenting Activity of Non-Langerhans Epidermal Cells in Contact Hypersensitivity Reactions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72263/1/j.1365-3083.1990.tb02914.x.pd

PASS2 version 4: An update to the database of structure-based sequence alignments of structural domain superfamilies

Accurate structure-based sequence alignments of distantly related proteins are crucial in gaining insight about protein domains that belong to a superfamily. The PASS2 database provides alignments of proteins related at the superfamily level and are characterized by low sequence identity. We thus report an automated, updated version of the superfamily alignment database known as PASS2.4, consisting of 1961 superfamilies and 10 569 protein domains, which is in direct correspondence with SCOP (1.75) database. Database organization, improved methods for efficient structure-based sequence alignments and the analysis of extreme distantly related proteins within superfamilies formed the focus of this update. Alignment of family-specific functional residues can be realized using such alignments and is shown using one superfamily as an example. The database of alignments and other related features can be accessed at http://caps.ncbs.res.in/pass2/

Administrators in higher education: organizational expansion in a transforming institution

Recent European research has revealed growth in the number of administrators and professionals across different sections of universities—a long established trend in US universities. We build on this research by investigating the factors associated with variation in the proportion of administrators across 761 Higher Education Institutions (HEIs) in 11 European countries. We argue that the enactment of expanded and diversified missions of HE is one of the main factors nurturing universities’ profesional and administrative bodies. Our findings support such an assertion; regardless of geographical and institutional differences, HEIs with high levels of “entrepreneurialism” (e.g. in service provision and external engagement) are characterized by a larger proportion of administrative staff. However, we find no empirical support for arguments citing structural pressures and demands on HEIs due to higher student enrolments, budget cuts or deregulation as engines driving such change. Instead, our results point towards, as argued by neo-institutionalists, the diffusion of formal organization as a model of institutional identity and purpose, which is especially prevalent at high levels of external connectedness

The Kafkaesque Pursuit of ‘World Class’: Audit Culture and the Reputational Arms Race in Academia

Since the 1980s universities have been subjected to a seemingly continuous process of policy reforms designed to make them more economical, efficient and effective, according to yardsticks defined by governments and university managers. The pursuit of ‘excellence’, ‘international standing’ and ‘world class’ status have become key drivers of what Hazelkorn (High Educ Pol 21(2):193–215, 2008) has termed the ‘rankings arms race’ that now dominates the world of academia. These policies are changing the mission and meaning of the public university and, more profoundly, the culture of academia itself. While some authors have sought to capture and analyse these trends in terms of ‘academic capitalism’ and the ‘enterprise university model’, we suggest they might also be usefully understood theoretically as illustrations of the rise of audit culture in higher education and its effects. Drawing on ethnographic examples from the UK, Denmark and New Zealand, we ask: how are higher education institutions being reconfigured by these new disciplinary regimes of audit? How are ranking and performance indicators changing institutional behaviour and transforming academic subjectivities? What possibilities are there for alternative university futures? And what insights can anthropology offer to address these questions

Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study

<p>Abstract</p> <p>Background</p> <p>In central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(<it>S</it>)-hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimer's disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory.</p> <p>Methods</p> <p>By high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH-Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S-OH-Chol levels.</p> <p>Results</p> <p>Compared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r²: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels.</p> <p>Conclusions</p> <p>Our results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia.</p

Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

Introduction Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined. Methods Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq). Results In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase. Conclusions We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72,694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, Large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), %body fat and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate-to-vigorous physical activity (MVPA), vigorous activity and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia and ponderal index, without heterogeneity (all: I-square=0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95%CI: 0.94, 0.98) respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. This article is protected by copyright. All rights reserved.Includes MRC, Wellcome Trust and NIHR