The collateral circulation of the heart

Abstract The coronary arteries have been regarded as end arteries for decades. However, there are functionally relevant anastomotic vessels, known as collateral arteries, which interconnect epicardial coronary arteries. These vessels provide an alternative source of blood supply to the myocardium in cases of occlusive coronary artery disease. The relevance of these collateral arteries is a matter of ongoing debate, but increasing evidence indicates a relevant protective role in patients with coronary artery disease. The collateral circulation can be assessed by different methods; the gold standard involves intracoronary pressure measurements. While the first clinical trials to therapeutically induce growth of collateral arteries have been unavailing, recent pilot studies using external counterpulsation or growth factors such as granulocyte colony stimulating factor (G-CSF) have shown promising results.http://deepblue.lib.umich.edu/bitstream/2027.42/112630/1/12916_2013_Article_799.pd

Single-cell analysis reveals regional reprogramming during adaptation to massive small bowel resection in mice

BACKGROUND & AIMS: The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or adapt ; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS. METHODS: Single-cell RNA sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH. RESULTS: Uniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factor Creb3l3 drive proximalization of cell identity in response to SBR. CONCLUSIONS: Adaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes-conceivably by engaging the retinoid metabolism pathway-merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS

Promoting ecological solutions for sustainable infrastructure

Sustainable infrastructure needs ecological solutions – it’s time to work together! We, the participants of the IENE 2020 International Conference, acknowledge that: 1. We are facing a significant worldwide expansion of transportation networks; this is especially the case in countries with developing economies. 2. If no action is taken, this global expansion will entail a substantial increase in greenhouse gas emissions, wildlife mortality and landscape fragmentation and change, with devastating effects on climate, biodiversity and ecosystem services. 3. Globally, ecosystem services are estimated to yield more than the Gross World Product of 2019 (https://www.worldometers.info/gdp/). 4. Despite the development and implementation of environmental impact assessment legislation, many existing transportation infrastructure networks are not environmentally friendly. These impacts are far-reaching with a debt being paid daily through unnecessary risks extendable to human health and well-being. 5.The economic, social, and ecological consequences of biodiversity loss and the role of transportation infrastructure is increasingly acknowledged worldwide: •Conservation and restoration of ecological connectivity is a major flagship in the preparation of the upcoming United Nations “Post-2020 Global biodiversity framework” following the recognised failure of the Aichi Targets associated with the loss and fragmentation of natural habitats (Target 5) (https://www.cbd.int/gbo5). •The European Green Deal and the new European Biodiversity Strategy for 2030, adopted by the European Commission in May 2020, stresses the need to develop a resilient Trans-European Nature Network supported by ecological corridors allowing the free flow of genes and individuals (https://ec.europa.eu/info/sites/info/files/communication-annex-eu-biodiversity-strategy-2030_en.pdf). •The Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) states that since 1970, transportation infrastructure is an important driver of land use change and associated loss of terrestrial biodiversity (https://ipbes.net/global-assessment). •The World Economic Forum 2020 recognised that biodiversity loss is one of the major threats with ‘plausible higher than average impact’ on Global Economies (https://www.weforum.org/reports/the-global-risks-report-2020). 6.To ahieve sustainability, infrastructure development must be decoupled from its negative effect on biodiversity. This requires immediate, stringent action and shared responsibilities from all stakeholders. 7.Regional, national, and worldwide networks of experts, including researchers, practitioners, landscape designers, and managers, address such concerns through knowledge-sharing platforms that promote effective ecological solutions. 8.The scarcity of collective and coordinated efforts, such as joint decision-making processes involving environmental, transportation, energy, policy and financing agencies, is still a major obstacle to achieve sustainability in transportation infrastructure projects.Comissão Europeia. Programa LIFE. Projeto LIFE LINES (LIFE14 NAT/PT/001081

Characterization of an H4N2 influenza virus from Quails with a multibasic motif in the hemagglutinin cleavage site

AbstractThe cleavage motif in the hemagglutinin (HA) protein of highly pathogenic H5 and H7 subtypes of avian influenza viruses is characterized by a peptide insertion or a multibasic cleavage site (MBCS). Here, we isolated an H4N2 virus from quails (Quail/CA12) with two additional arginines in the HA cleavage site, PEKRRTR/G, forming an MBCS-like motif. Quail/CA12 is a reassortant virus with the HA and neuraminidase (NA) gene most similar to a duck-isolated H4N2 virus, PD/CA06 with a monobasic HA cleavage site. Quail/CA12 required exogenous trypsin for efficient growth in culture and caused no clinical illness in infected chickens. Quail/CA12 had high binding preference for α2,6-linked sialic acids and showed higher replication and transmission ability in chickens and quails than PD/CA06. Although the H4N2 virus remained low pathogenic, these data suggests that the acquisition of MBCS in the field is not restricted to H5 or H7 subtypes

EGFR in enterocytes & endothelium and HIF1α in enterocytes are dispensable for massive small bowel resection induced angiogenesis

Background: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α). Methods: We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine. Results: Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine. Conclusions: Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types–enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS

Promoting ecological solutions for sustainable infrastructure

Linear infrastructure networks such as roads, railways, navigation and irrigation canals, and power lines have grown exponentially since the mid-20th century. Most of these networks built before the 1990s have a significant impact on the environment. While there is no doubt that humanity needs infrastructure to ensure safe, secure and sufficient access to food, water and energy, it is essential to prevent the loss of biodiversity and ecosystems which are also at the basis of the provision of such fundamental services. Those complex, interconnected issues cannot be tackled without research and innovation, both in the fields of biodiversity and of infrastructure.IENE (Infrastructure Ecology Network Europe) was set up in 1996 to meet this need. Its mission is to promote the exchange of knowledge, experience and best practice in safe and sustainable pan-European transport infrastructure. With a status of an association today, this independent network has more than 400 members consisting of researchers, engineers, decision makers and infrastructure operators. IENE functions as an international and interdisciplinary forum. It supports cross-border cooperation in research, mitigation, planning, design, construction and maintenance in the field of biodiversity and transport infrastructure.Every two years, IENE organises an international conference to present cutting-edge research, identify pressing issues and problems, discuss effective solutions and map out future activities in the field of transport ecology and infrastructure. We are very glad to present you in this special issue some of the best scientific outcomes of the IENE 2020 conference, hoping that it will contribute to further breakthroughs in science and uptake in policy-making and practices on the ground. We commend the organising team of the University of Evora, Portugal, for their excellent programming of the conference and for having gathered exceptional scientists on the topic of biodiversity and infrastructure. They managed to host a high-quality event, despite the many adjustments that had to be done because of the covid-19, including postponing the conference to January 2021 and holding it entirely online.The topic of IENE conference 2020 was “Linear Infrastructure Networks with Ecological Solutions” and the motto was “working together”. This means that every stakeholder has a role to play, and that biodiversity should be considered at all governance scales and during all phases of the set-up of infrastructure. The papers selected here are of particular interest to follow the path set forth in the conference’s final declaration, that is included in this issue

Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America

Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b underwent an explosive geographic expansion in 2021 among wild birds and domestic poultry across Asia, Europe, and Africa. By the end of 2021, 2.3.4.4b viruses were detected in North America, signifying further intercontinental spread. Here we show that the western movement of clade 2.3.4.4b was quickly followed by reassortment with viruses circulating in wild birds in North America, resulting in the acquisition of different combinations of ribonucleoprotein genes. These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement in mammals. The proclivity of the current A(H5N1) 2.3.4.4b virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants

Custom Integrated Circuits

Contains reports on six research projects.U.S. Air Force - Office of Scientific Research (Contract F49620-84-C-0004)Analog Devices, Inc.Defense Advanced Research Projects Agency (Contract N00014-80-C-0622)National Science Foundation (Grant ECS83-10941

Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project

The Numerical INJection Analysis (NINJA) project is a collaborative effort between members of the numerical relativity and gravitational-wave data analysis communities. The purpose of NINJA is to study the sensitivity of existing gravitational-wave search algorithms using numerically generated waveforms and to foster closer collaboration between the numerical relativity and data analysis communities. We describe the results of the first NINJA analysis which focused on gravitational waveforms from binary black hole coalescence. Ten numerical relativity groups contributed numerical data which were used to generate a set of gravitational-wave signals. These signals were injected into a simulated data set, designed to mimic the response of the Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this data using search and parameter-estimation pipelines. Matched filter algorithms, un-modelled-burst searches and Bayesian parameter-estimation and model-selection algorithms were applied to the data. We report the efficiency of these search methods in detecting the numerical waveforms and measuring their parameters. We describe preliminary comparisons between the different search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ