VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

Vascular endothelial growth factor (VEGF-A) is a major regulator of blood vessel formation and function. it controls several processes in endothelial cells, such as proliferation, survival, and migration, but it is not known how these are coordinately regulated to result in more complex morphogenetic events, such as tubular sprouting, fusion, and network formation. We show here that VEGF-A controls angiogenic sprouting in the early postnatal retina by guiding filopodial extension from specialized endothelial cells situated at the tips of the vascular sprouts. The tip cells respond to VEGF-A only by guided migration; the proliferative response to VEGF-A occurs in the sprout stalks. These two cellular responses are both mediated by agonistic activity of VEGF-A on VEGF receptor 2. Whereas tip cell migration depends on a gradient of VEGF-A, proliferation is regulated by its concentration. Thus, vessel patterning during retinal angiogenesis depends on the balance between two different qualities of the extracellular VEGF-A distribution, which regulate distinct cellular responses in defined populations of endothelial cells

Screening for Abdominal Aortic Aneurysm among Patients Referred to the Vascular Laboratory is Cost-effective

AbstractScreening for abdominal aortic aneurysm (AAA) in high-risk groups has been recommended based on a high prevalence of disease, while being questioned due to a high frequency of co-morbidities and inferior life-expectancy. We evaluated the long-term outcome and the cost-effectiveness of selective AAA screening among patients referred to the vascular laboratory for arterial examination.MethodsA total of 5924 patients, referred to the vascular laboratory of a university hospital, were screened for AAA with ultrasound (definition: ∅≥30mm), 1993–2005. Outcome data were gathered through hospital records and the national population registry. A Markov model was used for health–economic evaluation.ResultsAn AAA was detected in 181 patients (mean age 72.8 years), of whom 21.5% underwent elective repair (perioperative mortality 5.1%) after 7.5 years of follow-up. Four of six patients diagnosed with AAA rupture were operated upon. Relative 5-year survival compared with the general Swedish population, controlled for age and sex, was 80.4% (95% confidence interval (CI): 70.8–88.8). The cost-effectiveness was robust in base-case (11 084 Euro/life year gained) and in sensitivity analyses of prevalence, cost and survival.ConclusionsPatients in whom AAA was detected at selective screening had inferior long-term survival and were operated on less frequently, compared with AAA patients described in previous studies. Yet, selective screening at the vascular laboratory was cost-effective

Weed Species Trait Selection as Shaped by Region and Crop Diversity in Organically Managed Spring Cereals

Weeds remain a challenge in organic arable farming, as well as supply ecosystem services. The aim is to control weed densities while hosting a diverse and manageable weed community, preventing domination of few deleterious species. Therefore, we want to understand how specific species are stimulated, and which traits are selected for. This study focuses on crop diversity hypothesizing that (1) regions and (2) crop diversity function as filters for specific weed species traits. We conducted a weed monitoring in spring cereals over 2 years on organic farms in five northern European regions. Management and weed trait variables collected for the occurring species allowed an RLQ fourth-corner analysis. The weed communities were regionally specific, but trait selection was not observed, except in Latvia. Hence, the regional species pool provided different species with similar traits. Crop diversity within the management of spring cereals, such as undersowing and cereal frequency in the rotation, affected weed traits. The number of years under organic production selected no traits, although species numbers are known to increase. Hence, general weed species diversity increased, irrespective of traits. We conclude that organic management may support the agility within the weed community against selection of species and act as a buffer rather than as filter

Spatio-Temporal Mutational Profile Appearances of Swedish SARS-CoV-2 during the Early Pandemic

Background: During the COVID-19 pandemic, the virus evolved, and we therefore aimed to provide an insight into which genetic variants were enriched, and how they spread in Sweden. Methods: We analyzed 348 Swedish SARS-CoV-2 sequences freely available from GISAID obtained from 7 February 2020 until 14 May 2020. Results: We identified 14 variant sites >= 5% frequency in the population. Among those sites, the D936Y substitution in the viral Spike protein was under positive selection. The variant sites can distinguish 11 mutational profiles in Sweden. Nine of the profiles appeared in Stockholm in March 2020. Mutational profiles 3 (B.1.1) and 6 (B.1), which contain the D936Y mutation, became the predominant profiles over time, spreading from Stockholm to other Swedish regions during April and the beginning of May. Furthermore, Bayesian phylogenetic analysis indicated that SARS-CoV-2 could have emerged in Sweden on 27 December 2019, and community transmission started on February 1st with an evolutionary rate of 1.5425 x 10(-3)substitutions per year. Conclusions: Our study provides novel knowledge on the spatio-temporal dynamics of Swedish SARS-CoV-2 variants during the early pandemic. Characterization of these viral variants can provide precious insights on viral pathogenesis and can be valuable for diagnostic and drug development approaches

A Model System for In Vitro Studies of Bank Vole Borne Viruses

The bank vole (Myodes glareolus) is a common small mammal in Europe and a natural host for several important emerging zoonotic viruses, e.g. Puumala hantavirus (PUUV) that causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses are known to interfere with several signaling pathways in infected human cells, and HFRS is considered an immune-mediated disease. There is no in vitro-model available for infectious experiments in bank vole cells, nor tools for analyses of bank vole immune activation and responses. Consequently, it is not known if there are any differences in the regulation of virus induced responses in humans compared to natural hosts during infection. We here present an in vitro-model for studies of bank vole borne viruses and their interactions with natural host cell innate immune responses. Bank vole embryonic fibroblasts (VEFs) were isolated and shown to be susceptible for PUUV-infection, including a wild-type PUUV strain (only passaged in bank voles). The significance of VEFs as a model system for bank vole associated viruses was further established by infection studies showing that these cells are also susceptible to tick borne encephalitis, cowpox and Ljungan virus. The genes encoding bank vole IFN-β and Mx2 were partially sequenced and protocols for semi-quantitative RT-PCR were developed. Interestingly, PUUV did not induce an increased IFN-β or Mx2 mRNA expression. Corresponding infections with CPXV and LV induced IFN-β but not Mx2, while TBEV induced both IFN-β and Mx2

Limits on surface gravities of Kepler planet-candidate host stars from non-detection of solar-like oscillations

We present a novel method for estimating lower-limit surface gravities log g of Kepler targets whose data do not allow the detection of solar-like oscillations. The method is tested using an ensemble of solar-type stars observed in the context of the Kepler Asteroseismic Science Consortium. We then proceed to estimate lower-limit log g for a cohort of Kepler solar-type planet-candidate host stars with no detected oscillations. Limits on fundamental stellar properties, as provided by this work, are likely to be useful in the characterization of the corresponding candidate planetary systems. Furthermore, an important byproduct of the current work is the confirmation that amplitudes of solar-like oscillations are suppressed in stars with increased levels of surface magnetic activity.Comment: Accepted for publication in ApJ; 35 pages, 10 figures, 5 table