Structures of two fimbrial adhesins, AtfE and UcaD, from the uropathogen Proteus mirabilis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146321/1/ayd2jb5004.pd

Trophic roles of tadpoles in tropical Australian streams

Tadpoles can be abundant consumers in stream ecosystems, and may influence the structure and function of streams through their feeding activities and interactions with other organisms. To understand the contribution of tadpoles to stream functioning, and the potential impact of their loss, it is necessary to determine their diets and how they might influence food-web structure. Using gut-content analysis and stable-isotope analysis of N and C, we determined the main food sources and trophic positions of tadpoles of five native frog species, invertebrates, and fish in upland and lowland Australian Wet Tropics streams. Omnivory was prevalent among the tadpoles and invertebrates. Tadpoles consumed different food according to availability and nutrient quality, but assimilated mainly biofilm and algae. Most tadpoles and invertebrates assimilated the same high-quality foods. Food webs in upland riffles were simplified by local extinction of tadpoles, and were probably simplified in pools in the cooler months by seasonal decline in tadpole abundance. Food-web complexity was increased in some pools by the presence of predatory fish and a greater number of basal sources. As tadpoles are important seasonal components in stream food webs, their local extinction can greatly alter food-web structure and complexity and, possibly, processes such as leaf litter breakdown and sediment accumulation

Redshifts and Velocity Dispersions of Galaxy Clusters in the Horologium-Reticulum Supercluster

We present 118 new optical redshifts for galaxies in 12 clusters in the Horologium-Reticulum supercluster (HRS) of galaxies. For 76 galaxies, the data were obtained with the Dual Beam Spectrograph on the 2.3m telescope of the Australian National University at Siding Spring Observatory. After combining 42 previously unpublished redshifts with our new sample, we determine mean redshifts and velocity dispersions for 13 clusters, in which previous observational data were sparse. In six of the 13 clusters, the newly determined mean redshifts differ by more than 750 km/s from the published values. In the case of three clusters, A3047, A3109, and A3120, the redshift data indicate the presence of multiple components along the line of sight. The new cluster redshifts, when combined with other reliable mean redshifts for clusters in the HRS, are found to be distinctly bi-modal. Furthermore, the two redshift components are consistent with the bi-modal redshift distribution found for the inter-cluster galaxies in the HRS by Fleenor et al. (2005).Comment: 13 pages, 3 figures, Accepted to A

Proteobactin and a yersiniabactin-related siderophore mediate iron acquisition in Proteus mirabilis

Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes ( P  ≤  0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent siderophore system for producing a novel siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis , and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both siderophores. These findings clearly show that proteobactin and the yersiniabactin-related siderophore function as iron acquisition systems. Despite the activity of both siderophores, only mutants lacking the yersiniabactin-related siderophore have reduced fitness in vivo . The fitness requirement for the yersiniabactin-related siderophore during UTI shows, for the first time, the importance of siderophore production in vivo for P. mirabilis .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79111/1/MMI_7317_sm_FigS1-S2_TabS1-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79111/2/j.1365-2958.2010.07317.x.pd

Conceptual understanding of screen media parenting: report of a working group

Screen media (television, computers, and videogames) use has been linked to multiple child outcomes, including obesity. Parents can be an important influence on children\u27s screen use. There has been an increase in the number of instruments available to assess parenting in feeding and physical activity contexts, however few measures are available to assess parenting practices regarding children\u27s screen media use. A working group of screen media and parenting researchers convened at the preconference workshop to the 2012 International Society for Behavioral Nutrition and Physical Activity (ISBNPA) annual meeting, “Parenting Measurement: Current Status and Consensus Reports,” to identify and prioritize issues in assessing screen media parenting practices. The group identified that screen media use can pose different risks for children, depending on their age and developmental stage, across physiologic, psychosocial, and development outcomes. With that in mind, a conceptual framework of how parents may influence their child\u27s screen-viewing behaviors was proposed to include the screen media content, context of viewing, and amount viewed. A research agenda was proposed to prioritize a validation of the framework and enhance the ability of researchers to best assess parenting influences across the three domains of content, context and amount of children\u27s screen media use

Locus of Control and Negative Cognitive Styles in Adolescence as Risk Factors for Depression Onset in Young Adulthood:Findings From a Prospective Birth Cohort Study

Whilst previous observational studies have linked negative thought processes such as an external locus of control and holding negative cognitive styles with depression, the directionality of these associations and the potential role that these factors play in the transition to adulthood and parenthood has not yet been investigated. This study examined the association between locus of control and negative cognitive styles in adolescence and probable depression in young adulthood and whether parenthood moderated these associations. Using a UK prospective population-based birth cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC), we examined the association between external locus of control and negative cognitive styles in adolescence with odds of depression in 4,301 young adults using logistic regression models unadjusted and adjusted for potential confounding factors. Interaction terms were employed to examine whether parenthood (i.e., having become a parent or not) moderated these associations. Over 20% of young adults in our sample were at or above the clinical threshold indicating probable depression. For each standard deviation (SD) increase in external locus of control in adolescence, there was a 19% (95% CI: 8–32%) higher odds of having probable depression in young adulthood, after adjusting for various confounding factors including baseline mood and different demographic and life events variables. Similarly, for each SD increase in negative cognitive styles in adolescence, there was a 29% (95% CI: 16–44%) higher odds of having probable depression in the adjusted model. We found little evidence that parenthood status moderated the relationship between external locus of control or negative cognitive styles in adolescence and probable depression following adjustment for confounding factors. Effect estimates were comparable when performed in the complete case dataset. These findings suggest that having an external locus of control and holding negative cognitive styles in mid- to late adolescence is associated with an increased likelihood of probable depression in young adulthood

Assessing Children’s Dietary Pesticide Exposure: Direct Measurement of Pesticide Residues in 24-Hr Duplicate Food Samples

Background: The data presented here are a response to calls for more direct measurements of pesticide residues in foods consumed by children and provide an opportunity to compare direct measures of pesticide residues in foods representing actual consumption with those reported by the U.S. Department of Agriculture Pesticide Data Program. Objective: We measured pesticide residues in 24-hr duplicate food samples collected from a group of 46 young children participating in the Children’s Pesticide Exposure Study (CPES). Methods: Parents were instructed to collect 24-hr duplicate food samples of all conventional fruits, vegetables, and fruit juices equal to the quantity consumed by their children, similarly prewashed/prepared, and from the same source or batch. Individual or composite food items were analyzed for organophosphate (OP) and pyrethroid insecticide residues. Results: We collected a total of 239 24-hr duplicate food samples collected from the 46 CPES children. We found 14% or 5% of those food samples contained at least one OP or pyrethroid insecticide, respectively. We measured a total of 11 OP insecticides, at levels ranging from 1 to 387 ng/g, and three pyrethroid insecticides, at levels ranging from 2 to 1,133 ng/g, in children’s food samples. We found that many of the food items consumed by the CPES children were also on the list of the most contaminated food commodities reported by the Environmental Working Group. Conclusions: The frequent consumption of food commodities with episodic presence of pesticide residues that are suspected to cause developmental and neurological effects in young children supports the need for further mitigation

Uncertainty-Informed Deep Learning Models Enable High-Confidence Predictions for Digital Histopathology

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a novel, clinically-oriented approach to uncertainty quantification (UQ) for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs. squamous cell carcinoma and show that high-confidence predictions outperform predictions without UQ, in both cross-validation and testing on two large external datasets spanning multiple institutions. Our testing strategy closely approximates real-world application, with predictions generated on unsupervised, unannotated slides using predetermined thresholds. Furthermore, we show that UQ thresholding remains reliable in the setting of domain shift, with accurate high-confidence predictions of adenocarcinoma vs. squamous cell carcinoma for out-of-distribution, non-lung cancer cohorts

Human mucosal associated invariant T cells detect bacterially infected cells

Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtbuninfected individuals. Interestingly, these Mtb-reactive cells expressed the Va7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. © 2010 Gold et al

Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study

BACKGROUND Progranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison. METHODS The diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset. RESULTS Plasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0~ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0~ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7~ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0~ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others. CONCLUSIONS Progranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders. TRIAL REGISTRATION Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015