20 research outputs found

    Understanding differences in underrepresented minorities and first-generation student perceptions in the introductory biology classroom

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    We used quantitative methods to better understand the perceptions of students in an introductory biology course (Biology 101) at a small, liberal arts college (SLAC) that is also a primarily white institution (PWI). In pre/post surveys, we asked students questions related to their attitudes and beliefs about their professor, classmates, and Biology 101. We were especially interested in the responses and outcomes of underrepresented minorities (URM) and first-generation (FG) students. Our findings suggest URM and FG students have a decreased sense of belonging and increased perceptions of exclusion and differential treatment due to race. These findings can explain, in part, the disparity in Biology 101 grade and STEM (science, technology, engineering, and math) attrition

    Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

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    Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≄18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

    Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

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    Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∌6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous Îł-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the Îł-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

    Using personas and the ADKAR framework to evaluate a network designed to facilitate sustained change toward active learning in the undergraduate classroom

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    Abstract One promising practice for increasing active learning in undergraduate science education is the use of a mentoring network. The Promoting Active Learning and Mentoring (PALM) Network was launched with practitioners from several professional societies and disciplines to make changes in their teaching based on evidence-based practices and to encourage the members to reflect deeply on their teaching experiences. Members of the Network interviewed seven previous Fellows, 1 to 6 years after completing their fellowship, to better understand the value of the Network and how these interactions impacted their ability to sustain change toward more active teaching practices. The interviews resulted in the creation of three personas that reflect the kinds of educators who engaged with the Network: Neil the Novice, Issa the Isolated, and Etta the Expert. Key themes emerged from the interviews about how interactions with the PALM Network sustained change toward evidence-based teaching practices allowing the members to readily adapt to the online learning environment during the COVID-19 pandemic. Understanding how the personas intersect with the ADKAR model contributes to a better understanding of how mentoring networks facilitate transformative change toward active learning and can inform additional professional development programs

    Direct Monitoring of the Strand Passage Reaction of DNA Topoisomerase II Triggers Checkpoint Activation

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    <div><p>By necessity, the ancient activity of type II topoisomerases co-evolved with the double-helical structure of DNA, at least in organisms with circular genomes. In humans, the strand passage reaction of DNA topoisomerase II (Topo II) is the target of several major classes of cancer drugs which both poison Topo II and activate cell cycle checkpoint controls. It is important to know the cellular effects of molecules that target Topo II, but the mechanisms of checkpoint activation that respond to Topo II dysfunction are not well understood. Here, we provide evidence that a checkpoint mechanism monitors the strand passage reaction of Topo II. In contrast, cells do not become checkpoint arrested in the presence of the aberrant DNA topologies, such as hyper-catenation, that arise in the absence of Topo II activity. An overall reduction in Topo II activity (i.e. slow strand passage cycles) does not activate the checkpoint, but specific defects in the T-segment transit step of the strand passage reaction do induce a cell cycle delay. Furthermore, the cell cycle delay depends on the divergent and catalytically inert C-terminal region of Topo II, indicating that transmission of a checkpoint signal may occur via the C-terminus. Other, well characterized, mitotic checkpoints detect DNA lesions or monitor unattached kinetochores; these defects arise <i>via</i> failures in a variety of cell processes. In contrast, we have described the first example of a distinct category of checkpoint mechanism that monitors the catalytic cycle of a single specific enzyme in order to determine when chromosome segregation can proceed faithfully.</p></div

    Pre-school obesity is associated with an increased risk of childhood fracture: A longitudinal cohort study of 466,997 children and up to 11 years of follow-up in Catalonia, Spain

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    This study aimed to determine if having an overweight or obese range body mass index (BMI) at time of beginning school is associated with increased fracture incidence in childhood. A dynamic cohort was created from children presenting for routine preschool primary care screening, collected in the Information System for Research in Primary Care (SIDIAP) platform in Catalonia, Spain. Data were collected from 296 primary care centers representing 74% of the regional pediatric population. A total of 466,997 children (48.6% female) with a validated weight and height measurement within routine health care screening at age 4 years (±6 months) between 2006 and 2013 were included, and followed up to the age of 15, migration out of region, death, or until December 31, 2016. BMI was calculated at age 4 years and classified using WHO growth tables, and fractures were identified using previously validated ICD10 codes in electronic primary care records, divided by anatomical location. Actuarial lifetables were used to calculate cumulative incidence. Cox regression was used to investigate the association of BMI category and fracture risk with adjustment for socioeconomic status, age, sex, and nationality. Median follow‐up was 4.90 years (interquartile range [IQR] 2.50 to 7.61). Cumulative incidence of any fracture during childhood was 9.20% (95% confidence interval [CI] 3.79% to 14.61%) for underweight, 10.06% (9.82% to 10.29%) for normal weight, 11.28% (10.22% to 12.35%) for overweight children, and 13.05% (10.69% to 15.41%) for children with obesity. Compared with children of normal range weight, having an overweight and obese range BMI was associated with an excess risk of lower limb fracture (adjusted hazard ratio [HR] = 1.42 [1.26 to 1.59]; 1.74 [1.46 to 2.06], respectively) and upper limb fracture (adjusted HR = 1.10 [1.03 to 1.17]; 1.19 [1.07 to 1.31]). Overall, preschool children with an overweight or obese range BMI had increased incidence of upper and lower limb fractures in childhood compared with contemporaries of normal weight. © 2020 American Society for Bone and Mineral Research

    Defective T-Segment Transit may Activate the Mad2-Dependent Checkpoint.

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    <p>Cell cycle analyses showing that Top2<sup>L475A,L480P</sup> activates Mad2-dependent but Rad53-independent checkpoint signaling. <b>a</b>, Cartoon describing catalytic defect in Top2<sup>L475A,L480P</sup> which has a reduced rate of T-segment transport due to inefficient G-segment cleavage and DNA-gate opening. <b>b–d</b>, Population Assays: Histogram plots show average G2/M duration; see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003832#s3" target="_blank">Material and Methods</a> for statistical analysis. Western blots show each Top2 mutant relative to Tub1 loading control at G1 and G2. <i>a</i> values are significantly different to <i>b</i> values in the histogram plots. Strains with the same letter are not significantly different. <b>e–f</b>, Single-cell assays: <i>e</i>, plots of average spindle length versus time for single cells aligned on the x-axis at the time of SPB separation (<i>i.e.</i> at time point 12 min). Error bars show standard deviation of lengths. <i>f</i>, Histogram plots of average time interval between SPB separation and the initiation of spindle elongation in anaphase B (+/− s.e.).</p

    Checkpoint Activation <i>via</i> Top2-B44 Requires Initiation of the Strand Passage Reaction.

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    <p><b>a</b>, Cartoon describing the catalytic defect in Top2<sup>Y782F</sup> which cannot cleave G-segment DNA and thus performs non-productive cycles of ATP hydrolysis and N-gate closure/opening (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003832#pgen-1003832-g001" target="_blank">Figure 1</a> for complete Strand Passage Reaction and Key). <b>b–d</b>, Analysis of the kinetics of cell cycle progression (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003832#pgen-1003832-g003" target="_blank">Figure 3</a>) following depletion of Top2<sup>deg</sup> and release from G1 synchrony in cells expressing endogenous levels of the indicated mutant Top2 proteins. <b>b</b>, Population Assays: Histogram plots show average G2/M duration; see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003832#s3" target="_blank">Material and Methods</a> for statistical analysis. Western blots show each Top2 mutant relative to Tub1 loading control at G1 and G2. <i>a</i> values are significantly different to <i>b</i> values in the histogram plots. Strains with the same letter are not significantly different. <b>c–d</b>, Single-cell assays: <i>c</i>, plots of average spindle length versus time for single cells aligned on the x-axis at the time of SPB separation (<i>i.e.</i> at time point 12 min). Error bars show standard deviation of lengths. <i>d</i>, Histogram plots of average time interval between SPB separation and the initiation of spindle elongation in anaphase B (+/− s.e.).</p

    Top2-B44 is Defective in ATP Hydrolysis.

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    <p><b>a</b>, Cleavage activity of Top2-B44. Agarose gel electrophoresis of supercoiled (SC) plasmid DNA either untreated (C) or after incubation with purified wild type Top2 or Top2-B44 enzymes in the presence of increasing concentrations of etoposide (Etop). N = nicked forms, L = linear form. The linear form indicates plasmid that was cut by Top2 and re-ligation blocked by binding of etoposide to the Top2-DNA complex. <b>b</b>, Relaxation activity of Top2-B44. <i>Left panel</i>, Agarose gel electrophoresis of supercoiled (SC) plasmid DNA either untreated (C) or after 0–15 min. incubated with purified wild type Top2 or Top2-B44 enzymes. L = Linear form, R = relaxed topoisomers. <i>Right panel</i>, Quantification of relaxation activity of purified wild type (WT) Top2 or Top2-B44 (B44) enzymes versus time at 37°C and 28°C. <b>c</b>, Rate of ATP hydrolysis by wild type (WT) Top2 and Top2-B44 (B44) enzymes at 37°C and 28°C (measured by the release of free phosphate).</p

    Slow Strand Passage does not Activate the Mad2-Dependent Checkpoint in the Absence of a T-Segment Transit Defect.

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    <p>Analysis of cell cycle kinetics in <i>top2</i><sup>deg</sup> strains expressing Top2<sup>G738D</sup> and Top2<sup>P824S</sup> which have overall reduced rates of the catalytic cycle do not activate checkpoint signaling. <b>a</b>, Population Assays: Histogram plots show average G2/M duration; see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003832#s3" target="_blank">Material and Methods</a> for statistical analysis. Western blots show each Top2 mutant relative to Tub1 loading control at G1 and G2. <i>a</i> values are significantly different to <i>b</i> values in the histogram plots. Strains with the same letter are not significantly different. <b>b–c</b>, Single-cell assays: <i>b</i>, plots of average spindle length versus time for single cells aligned on the x-axis at the time of SPB separation (<i>i.e.</i> at time point 12 min). Error bars show standard deviation of lengths. <i>c</i>, Histogram plots of average time interval between SPB separation and the initiation of spindle elongation in anaphase B (+/− s.e.).</p
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