18 research outputs found

    There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator

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    Höhn S, Hallmann A. There is more than one way to turn a spherical cellular monolayer inside out: type B embryo inversion in Volvox globator. BMC Biology. 2011;9(1): 89.Background: Epithelial folding is a common morphogenetic process during the development of multicellular organisms. In metazoans, the biological and biomechanical processes that underlie such three-dimensional (3D) developmental events are usually complex and difficult to investigate. Spheroidal green algae of the genus Volvox are uniquely suited as model systems for studying the basic principles of epithelial folding. Volvox embryos begin life inside out and then must turn their spherical cell monolayer outside in to achieve their adult configuration; this process is called 'inversion.' There are two fundamentally different sequences of inversion processes in Volvocaceae: type A and type B. Type A inversion is well studied, but not much is known about type B inversion. How does the embryo of a typical type B inverter, V. globator, turn itself inside out? Results: In this study, we investigated the type B inversion of V. globator embryos and focused on the major movement patterns of the cellular monolayer, cell shape changes and changes in the localization of cytoplasmic bridges (CBs) connecting the cells. Isolated intact, sectioned and fragmented embryos were analyzed throughout the inversion process using light microscopy, confocal laser scanning microscopy, scanning electron microscopy and transmission electron microscopy techniques. We generated 3D models of the identified cell shapes, including the localizations of CBs. We show how concerted cell-shape changes and concerted changes in the position of cells relative to the CB system cause cell layer movements and turn the spherical cell monolayer inside out. The type B inversion of V. globator is compared to the type A inversion in V. carteri. Conclusions: Concerted, spatially and temporally coordinated changes in cellular shapes in conjunction with concerted migration of cells relative to the CB system are the causes of type B inversion in V. globator. Despite significant similarities between type A and type B inverters, differences exist in almost all details of the inversion process, suggesting analogous inversion processes that arose through parallel evolution. Based on our results and due to the cellular biomechanical implications of the involved tensile and compressive forces, we developed a global mechanistic scenario that predicts epithelial folding during embryonic inversion in V. globator

    Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

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    Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

    Noxious and Selected Invasive Plant Populations along Illinois Toll Highway Rights-of-Way

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    The Illinois Toll Highway Authority (ITHA) requested a survey during 2010 for noxious and selected invasive plant species established in ITHA rights-of-way throughout the tollway system in northern and northeastern Illinois. The species of concern provided by the ITHA include all species on the Illinois Noxious Weeds list (Illinois Noxious Weed Law,Administrative Code 2002) and selected invasive species recognized by the Illinois Invasive Plant Species Council (IIPSC). These total 15 species and include annuals, biennials, and perennial forbs and grasses (Table 1). The survey goals were to locate and estimate population sizes of these species within tollway rights-of-way with a focus on moderate to major concentrations to assist in targeted control efforts.Illinois Toll Highway Authority Grant/Contract No: 596616unpublishednot peer reviewe

    Development of an interpretive walkway at the University of Michigan

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    Master of ScienceLandscape ArchitectureUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/106241/1/39015018926751.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106241/2/39015018926751.pdfDescription of 39015018926751.pdf : Restricted to UM users only

    Competition from unseen or unheard novel words: Lexical consolidation across modalities

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    Item does not contain fulltextIn four experiments we investigated the formation of novel word memories across modalities, using competition between novel words and their existing phonological/orthographic neighbours as a test of lexical integration. Auditorily acquired novel words entered into competition both in the spoken modality (Experiment 1) and in the written modality (Experiment 4) after a consolidation period of 24 h. Words acquired from print, on the other hand, showed competition effects after 24 h in a visual word recognition task (Experiment 3) but required additional training and a consolidation period of a week before entering into spoken-word competition (Experiment 2). These cross-modal effects support the hypothesis that lexicalised rather than episodic representations underlie post-consolidation competition effects. We suggest that sublexical phoneme-grapheme conversion during novel word encoding and/or offline consolidation enables the formation of modality-specific lexemes in the untrained modality, which subsequently undergo the same cortical integration process as explicitly perceived word forms in the trained modality. Although conversion takes place in both directions, speech input showed an advantage over print both in terms of lexicalisation and explicit memory performance. In conclusion, the brain is able to integrate and consolidate internally generated lexical information as well as external perceptual input.15 p

    The role of apologies in professional discipline

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    We live in times of 'apology mania', says Lee Taft, or at least 'national conversation' about the role and meaning of apologies. Roy Brooks talks of an 'age of apology'. Some 10 years after these pronouncements, little has changed. Apologies are ubiquitous and debated in the public and political domain. And they continue to be used and imported into legal jurisdictions. For instance, legislation removes civil liability for saying 'sorry' in certain contexts and may reward apologies in mitigation of sentence
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