38 research outputs found

    Quantitative analysis of incorporation dynamics of conserved Centriole proteins in Drosophila early embryos

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    To divide efficiently, cells of animals and many other higher eukaryotes, rely upon centrosomes to help nucleate the bipolar mitotic spindle. At each division, two centrosomes are required, such that one centrosome is ultimately inherited by each daughter cell. Consequently, centrosomes must duplicate precisely once during each cycle of cell division. At the core of each centrosome is a mother centriole that can duplicate by growing a new daughter centriole off its side, which will later mature into a mother and nucleate its own centrosome. The core components of the centriole are highly conserved across higher eukaryotes, despite this there is still a lack of detail regarding their function and their hierarchy of assembly. In this thesis, I perform a comparative analysis of the incorporation dynamics of several conserved centriole proteins, using both standard and super-resolution microscopy, and the Drosophila early embryo as a model. I show that the daughter centrioles in the Drosophila early embryo appear to begin assembling earlier than previously reported. Further, I provide evidence that several core centriole proteins may be recruited into a transient centrosomal primordial “soup” in addition to the centriole proper. In addition, I refine the order of assembly of the centriole - allowing incorporation of Sas-6, Ana2, Ana3, CEP135, Ana1 and Asl to be placed on a continuous timeline alongside the cell cycle. Finally, through the use of CEP135 mutants, I show that, CEP135 does not appear to be necessary to recruit Ana1 into centrioles, in contrast to previous findings. In summary, my work redefines the initial incorporation dynamics of centriole assembly, challenging several previous assumptions and providing new avenues for interrogation of the specific functions of the core centriole proteins

    A Guide for Social Science Journal Editors on Easing into Open Science

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    Journal editors have a large amount of power to advance open science in their respective fields by incentivising and mandating open policies and practices at their journals. The Data PASS Journal Editors Discussion Interface (JEDI, an online community for social science journal editors: www.dpjedi.org) has collated several resources on embedding open science in journal editing (www.dpjedi.org/resources). However, it can be overwhelming as an editor new to open science practices to know where to start. For this reason, we created a guide for journal editors on how to get started with open science. The guide outlines steps that editors can take to implement open policies and practices within their journal, and goes through the what, why, how, and worries of each policy and practice. This manuscript introduces and summarizes the guide (full guide: https://osf.io/hstcx).<br/

    Perceptions About Work/Life Balance Among DU Community Members with Young Children

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    Background: In the past fifty years, families in the USA have changed in configuration, size and dynamics. The percentage of families that do not conform to the traditional family unit (married mother and father with children) has increased as there are more single-parent families, LGBTQ families and interracial families. The proportion of unmarried or divorced families has also increased, as it has the number of married and unmarried couples that opt to not have children and, additionally, more couples are opting for adoption and foster parenting (Pew Research Center 2010). Furthermore, the percentage of households where all the adults work has increased, which impacts the amount and quality of time available for family activities and household chores (Bianchi, Robinson and Milkie 2006). These and other trends have led to the identification of “work-family balance” as an important challenge of our times, one that families have been facing for decades and that institutions are only starting to pay attention to (Hochschild 2013). Although there are many aspects of family life that are challenging to balance with workplace demands, childcare has been specifically identified as one that needs attention (Desilver 2014). Methods: Study goal: To describe the perceptions that some DU community members with children have about work-family balance with attention to challenges, difficulties and institutional responses. Study design: Descriptive, cross-sectional, qualitative study. Population and sample: We recruited 63 University of Denver students (13), staff (14) and faculty (36) who are responsible of parenting at least one child under 10 years of age. We used purposive sampling. which consists in actively finding individuals who meet the criteria. Data collection: Semi structured interviews (January 23-February 8, 2017), in person, audio recorded and transcribed within one week. Participants’ autonomy, confidentiality and anonymity were protected throughout the process. Data analysis: Thematic analysis, which consists in the systematic identification of themes in the interview transcripts, followed by their conceptual organization and hierarchization. Research team: sixty-six undergraduate students taking Cultural Anthropology (ANTH 2010) in winter 2017, four graduate teaching assistants and one course instructor. Findings: Student participants portrayed work/life balance as set of interconnected situations and relations that go from the deeply personal to the interpersonal, communal and institutional. Aiming at capturing such complexity, we organized our findings in four themes: work/life balance, family dynamics, personal challenges and support. Participants told us about their struggles when negotiating work and life responsibilities which often lead to feelings of guilt, which are mediated by their colleagues’ reactions, schedule flexibility, their job situation and the presence or absence of maternity leave. Family dynamics reflected a tension between a narrative of independence and one of dependence in raising children, highlighting the importance of social networks, both of which are also affected by immigration status and intra-household negotiations particularly, Perceptions about work/life balance among DU community members with young children Cultural Anthropology (ANTH 2010) winter 2017 4 with their partners. Personal challenges relate primarily with time management and establishing clear boundaries between work and family, which related to managing emails, organization and scheduling of activities, maintaining a financial balance, and solving transportation needs, all of which were mediated the ability parents have of controlling a flexible work schedule, an ability greatly diminished among students. Support parents need related to child care goes from the one that happens in interpersonal interactions with neighbors, friends, relatives and colleagues, to the institutionalized forms of support, where participants expressed their frustration for the insufficiency of accessible options in Denver, the lack of options at DU, and the inaccessibility of DU’s Fisher Early Learning Center. Conclusions and recommendations: Participant’s ability to control their schedules together with their financial and social capital seem to shape important differences in the ability that parents have for balancing work and life. Students, single parents and recent immigrants seem to have a combination of elements that add to the challenges. At the interpersonal level, simple acts of kindness, sympathy and empathy in the everyday interactions seem to make an important difference to parents. The perception that many of the student participants expressed about the academy not being comfortable with children, families or parents could be addressed by making it normal to talk about all these aspects of life. At the institutional level, efforts could be made at reaching out to parents, especially students and single parents, to offer them guidance and support that is already in place at DU, such as counselling and wellbeing resources, as well as orientation related to institutional policies. Policies related to maternity and paternity leave should be refined to ensure that they do not negatively affect those they are supposed to support. Convenient, affordable and sustainable on-campus child care options should be seriously considered given that they would enhance the possibilities for parents to participate in activities at DU. Events should be organized where members of the DU community have the opportunity to share not as students, staff or faculty, but as members of families

    Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

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    Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

    Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension: randomised controlled trial

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    Objective: The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design: Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting: 76 general practices in the United Kingdom. Participants: 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions: Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures: The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results: After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of −3.4 mm Hg (95% confidence interval −6.1 to −0.8 mm Hg) and a mean difference in diastolic blood pressure of −0.5 mm Hg (−1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions: The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration: ISRCTN13790648

    The influence of diet on gut microbiome and body mass dynamics in a capital-breeding migratory bird

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    Gut-associated microbial communities are known to play a vital role in the health and fitness of their hosts. Though studies investigating the factors associated with among-individual variation in microbiome structure in wild animal species are increasing, knowledge of this variation at the individual level is scarce, despite the clear link between microbiome and nutritional status uncovered in humans and model organisms. Here, we combine detailed observational data on life history and foraging preference with 16S rRNA profiling of the faecal microbiome to investigate the relationship between diet, microbiome stability and rates of body mass gain in a migratory capital-breeding bird, the light-bellied Brent goose (Branta bernicla hrota). Our findings suggest that generalist feeders have microbiomes that are intermediate in diversity and composition between two foraging specialisms, and also show higher within-individual plasticity. We also suggest a link between foraging phenotype and the rates of mass gain during the spring staging of a capital breeder. This study offers rare insight into individual-level temporal dynamics of the gut microbiome of a wild host. Further work is needed to uncover the functional link between individual dietary choices, gut microbiome structure and stability, and the implications this has for the reproductive success of this capital breeder
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