Determination of Endothelial Stalk versus Tip Cell Potential during Angiogenesis by H2.0-like Homeobox-1

SummaryTissue branching morphogenesis requires the hierarchical organization of sprouting cells into leading “tip” and trailing “stalk” cells [1, 2]. During new blood vessel branching (angiogenesis), endothelial tip cells (TCs) lead sprouting vessels, extend filopodia, and migrate in response to gradients of the secreted ligand, vascular endothelial growth factor (Vegf) [3]. In contrast, adjacent stalk cells (SCs) trail TCs, generate the trunk of new vessels, and critically maintain connectivity with parental vessels. Here, we establish that h2.0-like homeobox-1 (Hlx1) determines SC potential, which is critical for angiogenesis during zebrafish development. By combining a novel pharmacological strategy for the manipulation of angiogenic cell behavior in vivo with transcriptomic analyses of sprouting cells, we identify the uniquely sprouting-associated gene, hlx1. Expression of hlx1 is almost entirely restricted to sprouting endothelial cells and is excluded from adjacent nonangiogenic cells. Furthermore, Hlx1 knockdown reveals its essential role in angiogenesis. Importantly, mosaic analyses uncover a cell-autonomous role for Hlx1 in the maintenance of SC identity in sprouting vessels. Hence, Hlx1-mediated maintenance of SC potential regulates angiogenesis, a finding that may have novel implications for sprouting morphogenesis of other tissues

Transforming the supervision of Hong Kong’s English language teachers

Uni-directional top-down traditional, approaches to the supervision of teachers limit the engagement of the teachers in reflecting upon their own practice and professional growth. Acheson & Gall (1992) recommend a three-phase approach to teacher supervision which includes […] classroom observation and feedback conference. Such […] emphasizes a more dynamic and constructivist approach to empower teachers to transform their practice and identify directions […] professional development. What happens when this and other approaches are adapted and applied by teachers in different contexts? This as well as other issues and concerns related to the supervision of language teachers in Hong Kong are addressed in this paper […] secondary school teachers of English with different roles, along with their course tutor discuss the strengths and problems of applying different supervisory approaches in a three-week practicum. The writer […] that the clinical supervision approach was conducive to support teachers\u27 professional development when used in conjunction with directive as well as· non-directive approaches. However, the teaching the non-directive approaches to be most difficult to carry out part with less-experienced teachers. From critiques of supervisor transcriptions, recommendations are made for improving the clinical supervision and teacher professional development in Hong Kong

Analysis of inhibitor of apoptosis protein family expression during mammary gland development

<p>Abstract</p> <p>Background</p> <p>Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. Here we examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution.</p> <p>Results</p> <p>Six out of eight mammalian IAP family members are expressed in the mammary gland. Notably, quantitative PCR and immunoblotting revealed that XIAP, c-IAP1 and c-IAP2 are down-regulated in pregnancy and lactation, and prior to the onset of involution. In cultured mammary epithelial cells (MECs), XIAP levels decreased in response to inhibition of growth factor signalling. Maintaining XIAP levels in MECs by expressing exogenous XIAP protected them from all apoptotic stimuli tested.</p> <p>Conclusions</p> <p>These data suggest that the developmental regulation of IAP expression <it>in vivo </it>contributes to naturally occurring programmes of cell death.</p

Internal gamma gamma-opacity in Active Galactic Nuclei and the consequences for the TeV observations of M87 and Cen A

Low Luminosity Active Galactic Nuclei (LLAGNs) possess the characteristic features of more luminous Active Galactic Nuclei (AGNs) but exhibit a much lower nuclear Halpha luminosity than their more luminous counterparts. M87 (NGC 4486) and Centaurus A (NGC 5128, CenA) are well-studied nearby LLAGNs. As an additional feature they show gamma-radiation up to TeV (10^{12}eV) energies, but the origin of this radiation is not resolved. The coincident observation of a radio and TeV flare in M87 suggests that the TeV radiation is produced within around 50-100 gravitational radii of the central supermassive black hole, depending on the assumed value of the mass of the black hole. Strong radiation fields can be produced in the central region of an (LL)AGN, e.g., by the accretion flow around the black hole, the jet plasma, or stars closely orbiting the black hole. These radiation fields can lead to the absorption of emitted TeV photons, and in fact high optical depths of such fields can make TeV detection from inner regions impossible. In this paper we consider the accretion flow around the black hole as the most prominent source for such a radiation field and we accordingly calculate the probability for absorption of TeV photons produced near the black holes in M87 and CenA assuming a low luminosity Shakura-Sunyaev Disk (SSD). We find that the results are very different for between the two LLAGNs. While the inner region of M87 is transparent for TeV radiation up to 15TeV, the optical depth in CenA is >> 1, leading to an absorption of TeV photons that might be produced near the central black hole. These results imply either that the TeV gamma production sites and processes are different for both sources, or that LLAGN black holes do not accrete (at least only) in form of a low luminosity SSD.Comment: accepted for publication in Ap

DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions

Regulation of transcription occurs in a cell type specific manner orchestrated by epigenetic mechanisms including DNA methylation. Methylation changes may also play a key role in lineage specification during stem cell differentiation. To further our understanding of epigenetic regulation in chondrocytes we characterised the DNA methylation changes during chondrogenesis of mesenchymal stem cells (MSCs) by Infinium 450 K methylation array. Significant DNA hypomethylation was identified during chondrogenic differentiation including changes at many key cartilage gene loci. Integration with chondrogenesis gene expression data revealed an enrichment of significant CpGs in upregulated genes, while characterisation of significant CpG loci indicated their predominant localisation to enhancer regions. Comparison with methylation profiles of other tissues, including healthy and diseased adult cartilage, identified chondrocyte-specific regions of hypomethylation and the overlap with differentially methylated CpGs in osteoarthritis. Taken together we have associated DNA methylation levels with the chondrocyte phenotype. The consequences of which has potential to improve cartilage generation for tissue engineering purposes and also to provide context for observed methylation changes in cartilage diseases such as osteoarthritis

Local control of intestinal stem cell homeostasis by enteroendocrine cells in the adult <i>Drosophila</i> midgut

Background: Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.&lt;p&gt;&lt;/p&gt; Results: Here we report a novel function of enteroendocrine cells acting as local regulators of intestinal stem cell (ISC) proliferation through modulation of the mesenchymal stem cell niche in the &lt;i&gt;Drosophila&lt;/i&gt; midgut. This paracrine signaling acts to constrain ISC proliferation within the epithelial compartment. Mechanistically, midgut enteroendocrine cells secrete the neuroendocrine hormone Bursicon, which acts—beyond its known roles in development—as a paracrine factor on the visceral muscle (VM). Bursicon binding to its receptor, DLGR2, the ortholog of mammalian leucine-rich repeat-containing G protein-coupled receptors (LGR4-6), represses the production of the VM-derived EGF-like growth factor Vein through activation of cAMP.&lt;p&gt;&lt;/p&gt; Conclusions: We therefore identify a novel paradigm in the regulation of ISC quiescence involving the conserved ligand/receptor Bursicon/DLGR2 and a previously unrecognized tissue-intrinsic role of enteroendocrine cells.&lt;p&gt;&lt;/p&gt

Relationship between volume status and blood pressure during chronic hemodialysis

Relationship between volume status and blood pressure during chronic hemodialysis.BackgroundThe relationship between volume status and blood pressure (BP) in chronic hemodialysis (HD) patients remains incompletely understood. Specifically, the effect of interdialytic fluid accumulation (or intradialytic fluid removal) on BP is controversial.MethodsWe determined the association of the intradialytic decrease in body weight (as an indicator of interdialytic fluid gain) and the intradialytic decrease in plasma volume (as an indicator of postdialysis volume status) with predialysis and postdialysis BP in a cross-sectional analysis of a subset of patients (N = 468) from the Hemodialysis (HEMO) Study. Fifty-five percent of patients were female, 62% were black, 43% were diabetic and 72% were prescribed antihypertensive medications. Dry weight was defined as the postdialysis body weight below which the patient developed symptomatic hypotension or muscle cramps in the absence of edema. The intradialytic decrease in plasma volume was calculated from predialysis and postdialysis total plasma protein concentrations and was expressed as a percentage of the plasma volume at the beginning of HD.ResultsPredialysis systolic and diastolic BP values were 153.1 ± 24.7 (mean ± SD) and 81.7 ± 14.8mm Hg, respectively; postdialysis systolic and diastolic BP values were 136.6 ± 22.7 and 73.9 ± 13.6mm Hg, respectively. As a result of HD, body weight was reduced by 3.1 ± 1.3kg and plasma volume was contracted by 10.1 ± 9.5%. Multiple linear regression analyses showed that eachkg reduction in body weight during HD was associated with a 2.95mm Hg (P = 0.004) and a 1.65mm Hg (P = NS) higher predialysis and postdialysis systolic BP, respectively. In contrast, each 5% greater contraction of plasma volume during HD was associated with a 1.50mm Hg (P = 0.026) and a 2.56mm Hg (P < 0.001) lower predialysis and postdialysis systolic BP, respectively. The effects of intradialytic decreases in body weight and plasma volume were greater on systolic BP than on diastolic BP.ConclusionsHD treatment generally reduces BP, and these reductions in BP are associated with intradialytic decreases in both body weight and plasma volume. The absolute predialysis and postdialysis BP levels are influenced differently by acute intradialytic decreases in body weight and acute intradialytic decreases in plasma volume; these parameters provide different information regarding volume status and may be dissociated from each other. Therefore, evaluation of volume status in chronic HD patients requires, at minimum, assessments of both interdialytic fluid accumulation (or the intradialytic decrease in body weight) and postdialysis volume overload

Disentangling diverse responses to climate change among global marine ecosystem models

Climate change is warming the ocean and impacting lower trophic level (LTL) organisms. Marine ecosystem models can provide estimates of how these changes will propagate to larger animals and impact societal services such as fisheries, but at present these estimates vary widely. A better understanding of what drives this inter-model variation will improve our ability to project fisheries and other ecosystem services into the future, while also helping to identify uncertainties in process understanding. Here, we explore the mechanisms that underlie the diversity of responses to changes in temperature and LTLs in eight global marine ecosystem models from the Fisheries and Marine Ecosystem Model Intercomparison Project (FishMIP). Temperature and LTL impacts on total consumer biomass and ecosystem structure (defined as the relative change of small and large organism biomass) were isolated using a comparative experimental protocol. Total model biomass varied between −35% to +3% in response to warming, and -17% to +15% in response to LTL changes. There was little consensus about the spatial redistribution of biomass or changes in the balance between small and large organisms (ecosystem structure) in response to warming, an LTL impacts on total consumer biomass varied depending on the choice of LTL forcing terms. Overall, climate change impacts on consumer biomass and ecosystem structure are well approximated by the sum of temperature and LTL impacts, indicating an absence of nonlinear interaction between the models’ drivers. Our results highlight a lack of theoretical clarity about how to represent fundamental ecological mechanisms, most importantly how temperature impacts scale from individual to ecosystem level, and the need to better understand the two-way coupling between LTL organisms and consumers. We finish by identifying future research needs to strengthen global marine ecosystem modelling and improve projections of climate change impacts

Differing marine animal biomass shifts under 21st century climate change between Canada's three ocean

Identificadors digitals: Digital object identifier for the 'European Research Council' (http://dx.doi.org/10.13039/501100000781) and Digital object identifier for 'Horizon 2020' (http://dx.doi.org/10.13039/501100007601)Unidad de excelencia María de Maeztu CEX2019-000940-MUnder climate change, species composition and abundances in high-latitude waters are expected to substantially reconfigure with consequences for trophic relationships and ecosystem services. Outcomes are challenging to project at national scales, despite their importance for management decisions. Using an ensemble of six global marine ecosystem models we analyzed marine ecosystem responses to climate change from 1971 to 2099 in Canada's Exclusive Economic Zone (EEZ) under four standardized emissions scenarios. By 2099, under business-as-usual emissions (RCP8.5) projected marine animal biomass declined by an average of −7.7% (±29.5%) within the Canadian EEZ, dominated by declines in the Pacific (−24% ± 24.5%) and Atlantic (−25.5% ± 9.5%) areas; these were partially compensated by increases in the Canadian Arctic (+26.2% ± 38.4%). Lower emissions scenarios projected successively smaller biomass changes, highlighting the benefits of stronger mitigation targets. Individual model projections were most consistent in the Atlantic and Pacific, but highly variable in the Arctic due to model uncertainties in polar regions. Different trajectories of future marine biomass changes will require regional-specific responses in conservation and management strategies, such as adaptive planning of marine protected areas and species-specific management plans, to enhance resilience and rebuilding of Canada's marine ecosystems and commercial fish stocks

The Undergraduate Training in Genomics (UTRIG) Initiative: Early & Active Training for Physicians in the Genomic Medicine Era

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG\u27s collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration