Structural parameters for globular clusters in NGC 5128. III. ACS surface-brightness profiles and model fits

We present internal surface-brightness profiles, based on HST/ACS imaging in the F606W bandpass, for 131 globular cluster (GC) candidates with luminosities 10^4 - 3 x 10^6 solar, in the giant elliptical galaxy NGC 5128. Several structural models are fit to the profile of each cluster and combined with mass-to-light ratios from population-synthesis models, to derive a catalogue of fundamental structural and dynamical parameters parallel in form to the catalogues recently produced by McLaughlin & van der Marel and Barmby et al. for GCs and massive young star clusters in Local Group galaxies. As part of this, we provide corrected and extended parameter estimates for another 18 clusters in NGC 5128, which we observed previously. We show that, like GCs in the Milky Way and some of its satellites, the majority of globulars in NGC 5128 are well fit by isotropic Wilson models, which have intrinsically more distended envelope structures than the standard King lowered isothermal spheres. We use our models to predict internal velocity dispersions for every cluster in our sample. These predictions agree well in general with the observed dispersions in a small number of clusters for which spectroscopic data are available. In a subsequent paper, we use these results to investigate scaling relations for GCs in NGC 5128.Comment: MNRAS, in press. 28 pages. Full data tables available at http://www.astro.keele.ac.uk/~dem/clusters.htm

Lowering of amyloid beta peptide production with a small molecule inhibitor of amyloid-? precursor protein dimerization

The amyloid ? precursor protein (APP) is a single-pass transmembrane glycoprotein that is ubiquitously expressed in many cell types, including neurons. Amyloidogenic processing of APP by ?- and ?-secretases leads to the production of amyloid-? (A?) peptides that can oligomerize and aggregate into amyloid plaques, a characteristic hallmark of Alzheimer’s disease (AD) brains. Multiple reports suggest that dimerization of APP may play a role in A? production; however, it is not yet clear whether APP dimers increase or decrease A? and the mechanism is not fully understood. To better understand the relationship between APP dimerization and production of A?, a high throughput screen for small molecule modulators of APP dimerization was conducted using APP-Firefly luciferase enzyme complementation to detect APP dimerization. Selected modulators identified from a compound library of 77,440 compounds were tested for their effects on A? generation. Two molecules that inhibited APP dimerization produced a reduction in A? levels as measured by ELISA. The inhibitors did not change sAPP? or ?-CTF levels, but lowered sAPP? levels, suggesting that blocking the dimerization is preventing the cleavage by ?-secretase in the amyloidogenic processing of APP. To our knowledge, this is the first High Throughput Screen (HTS) effort to identify small molecule modulators of APP dimerization. Inhibition of APP dimerization has previously been suggested as a therapeutic target in AD. The findings reported here further support that modulation of APP dimerization may be a viable means of reducing the production of A?

Impact of different mass drug administration strategies for gaining and sustaining control of <i>Schistosoma mansoni</i> and <i>Schistosoma haematobium</i> infection in Africa

This report summarizes the design and outcomes of randomized controlled operational research trials performed by the Bill & Melinda Gates Foundation-funded Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) from 2009 to 2019. Their goal was to define the effectiveness and test the limitations of current WHO-recommended schistosomiasis control protocols by performing large-scale pragmatic trials to compare the impact of different schedules and coverage regimens of praziquantel mass drug administration (MDA). Although there were limitations to study designs and performance, analysis of their primary outcomes confirmed that all tested regimens of praziquantel MDA significantly reduced local; Schistosoma; infection prevalence and intensity among school-age children. Secondary analysis suggested that outcomes in locations receiving four annual rounds of MDA were better than those in communities that had treatment holiday years, in which no praziquantel MDA was given. Statistical significance of differences was obscured by a wider-than-expected variation in community-level responses to MDA, defining a persistent hot spot obstacle to MDA success. No MDA schedule led to elimination of infection, even in those communities that started at low prevalence of infection, and it is likely that programs aiming for elimination of transmission will need to add supplemental interventions (e.g., snail control, improvement in water, sanitation and hygiene, and behavior change interventions) to achieve that next stage of control. Recommendations for future implementation research, including exploration of the value of earlier program impact assessment combined with intensification of intervention in hot spot locations, are discussed

ENCODE whole-genome data in the UCSC genome browser (2011 update)

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access

Reciprocal elucidation: a student-led pedagogy in multidisciplinary undergraduate research conferences

© 2016 HERDSA. There is no previous study of the benefits of attending a national multidisciplinary conference dedicated to undergraduate researchers, despite the growing number of such conferences internationally. This paper addresses the gap in knowledge of the learning gains from these conferences, and reveals a student driven learning process, a multidisciplinary signature pedagogy. It presents the results of 90 in-depth interviews with student conference participants conducted over three consecutive years of a multidisciplinary National Conference of Undergraduate Research (2012–2014). This paper uniquely captures the student voice on their perceived learning gains from this experience. The results reveal that some students co-create a pedagogy of Foucauldian reciprocal elucidation, through a sense of ‘unfinishedness’, allowing them to reflect on their own learning in the light of divergent perspectives, questions and frames of reference. Bidirectional exchange of ideas and insights enabled students to ask and answer questions that transformed each other’s thinking, allowing them to arrive at understandings they could not have achieved by themselves. The opportunity to present research in an authentic setting beyond disciplinary and institutional contexts developed students’ skills and confidence, giving additional value over and above the recognised benefits of engaging in research. The undergraduate research conference is framed as a threshold experience for the development of self-authorship. Significant implications for practice include supporting constructive dialogues between students and the creation of authentic and professional multidisciplinary contexts for sharing research

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Family and Neighbourhood Socioeconomic Inequalities in Childhood Trajectories of BMI and Overweight: Longitudinal Study of Australian Children

Background:Socioeconomic inequalities in longitudinal patterning of childhood overweight could cause marked differentials in total burden by adulthood. This study aims to determine timing and strength of the association between socioeconomic status (SES) and children's body mass index (BMI) in the pre- and primary school years, and to examine socioeconomic differences in overweight trajectories across childhood.Methods:Participants were 4949 children from the Longitudinal Study of Australian Children. BMI was measured at four biennial waves starting at age 4-5 years in 2004. Developmental trajectories of childhood overweight were identified with latent class analyses. Composite variables of family and neighbourhood SES were used.Results:Socioeconomic differences in mean BMI z-scores already present at age 4-5 more than doubled by age 10-11 years, reflecting decreasing mean BMI among advantaged rather than increasing means among disadvantaged children. Latent class analysis identified children with 'stable normal weight' (68%), and with 'persistent' (15%), 'late-onset' (14%), and 'resolving' overweight (3%). Risks of persistent and late-onset childhood overweight were highest among low SES families (e.g. most disadvantaged quintile: ORpersistent= 2.51, 95%CI: 1.83-3.43), and only partly explained by birth weight and parental overweight. Relationships with neighbourhood SES were weaker and attenuated fully on adjustment for family SES. No socioeconomic gradient was observed for resolving overweight.Conclusions:Childhood has become the critical period when socioeconomic inequalities in overweight emerge and strengthen. Although targeting disadvantaged children with early overweight must be a top priority, the presence of childhood overweight even among less-disadvantaged families suggests only whole-society approaches will eliminate overweight-associated morbidity

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Magnesium and calcium overaccumulate in the leaves of a schengen3 mutant of Brassica rapa

Magnesium (Mg) and calcium (Ca) are essential mineral nutrients poorly supplied in many human food systems. In grazing livestock, Mg and Ca deficiencies are costly welfare issues. Here, we report a Brassica rapa loss-of-function schengen3 (sgn3) mutant, braA.sgn3.a-1, which accumulates twice as much Mg and a third more Ca in its leaves. We mapped braA.sgn3.a to a single recessive locus using a forward ionomic screen of chemically mutagenized lines with subsequent backcrossing and linked-read sequencing of second back-crossed, second filial generation (BC2F2) segregants. Confocal imaging revealed a disrupted root endodermal diffusion barrier, consistent with SGN3 encoding a receptor-like kinase required for normal formation of Casparian strips, as reported in thale cress (Arabidopsis thaliana). Analysis of the spatial distribution of elements showed elevated extracellular Mg concentrations in leaves of braA.sgn3.a-1, hypothesized to result from preferential export of excessive Mg from cells to ensure suitable cellular concentrations. This work confirms a conserved role of SGN3 in controlling nutrient homeostasis in B. rapa, and reveals mechanisms by which plants are able to deal with perturbed shoot element concentrations resulting from a “leaky” root endodermal barrier. Characterization of variation in leaf Mg and Ca accumulation across a mutagenized population of B. rapa shows promise for using such populations in breeding programs to increase edible concentrations of essential human and animal nutrients

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

Approximately 200 million people have schistosomiasis in parts of Africa, South America, the Middle East, the Caribbean and Asia. Several studies of multiple treatments and reinfections indicate that some people develop resistance to reinfection. Of all the immunologic findings associated with such studies, the most consistent observation is that resistance (usually defined as lower levels of infection upon reinfection) correlates with high IgE and low IgG4 antibodies against schistosome antigens. Our studies test whether single nucleotide polymorphisms residing in the gene or promoter regions of cytokines pivotal in controlling production of these antibody isotypes are different amongst those that develop resistance to reinfection as opposed to those that do not. Through genotyping of these polymorphisms in a cohort of occupationally exposed car washers, we found that men with certain genotypic patterns of polymorphisms in IL-4, IFN-γ, and IL-13 were significantly more likely to be resistant to reinfection than those with different patterns. These data provide initial insights into the potential genetic foundation of propensities of people to develop resistance to reinfection by schistosomes, and offer a basis for further molecular studies of how these polymorphisms might work at the transcriptional and gene product level in cells stimulated by schistosome antigens