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

Antibiotic use, knowledge, and practices of milk vendors in India's informal dairy value chain

BackgroundMilk vendors play an important role in India's dairy value chain; however, their food safety practices are poorly understood. From a milk safety perspective, vendor behavior is significant because it has the potential to affect both consumer and producer behavior. This study describes the types of milk vendors in two Indian states, in an attempt to investigate vendors' hygienic knowledge and practices toward safety and antimicrobial resistance (AMR). MethodsA cross-sectional study was conducted in the states of Assam and Haryana, India. In selected villages, all the milk vendors identified at the time of visit were interviewed. A questionnaire was used to assess the knowledge and practices on antibiotics, milk safety and hygiene. The milk samples were tested for presence of antibiotic resistant bacteria using antibiotic susceptibility testing. ResultsIn total, 244 milk vendors were interviewed during the survey. Out of these, 146 (59.8%) of the vendors traded raw milk, while 40.2% traded pasteurized milk. Vendors were categorized depending on whom they supplied milk to. Five categories were identified: (a) those who sold at grocery shops; (b) those who sold on roadside (roadside vendors); (c) those who sold from door to door; (d) those who sold to sweet makers/tea stalls, and (e) those who sold from own home/other entity. The level of training among vendors on milk hygiene was non-existent and the knowledge related to antibiotics was low. Most of them [210/244 (86.07%)] agreed that boiled milk is always safer than raw milk but almost half [119 (48.77%)] of them admitted that sometimes they drink milk without boiling it. Most vendors believed that they could identify whether milk is safe or not for consumption just by its appearance and smell. Out of 124 milk samples collected from surveyed milk vendors and tested for the presence of antibiotic-resistant bacteria, 80 (64.52%) were tested positive. ConclusionThis study highlights the low levels of knowledge regarding food safety among milk vendors. It shows the predominance of informal milk vendors in the surveyed states and prevalence of AMR bacteria in milk traded by them. Training may be a beneficial strategy for addressing the issue

γ-Secretase modulators show selectivity for γ-secretase–mediated amyloid precursor protein intramembrane processing

The aggregation of β-amyloid peptide 42 results in the formation of toxic oligomers and plaques, which plays a pivotal role in Alzheimer's disease pathogenesis. Aβ42 is one of several Aβ peptides, all of Aβ30 to Aβ43 that are produced as a result of γ-secretase–mediated regulated intramembrane proteolysis of the amyloid precursor protein. γ-Secretase modulators (GSMs) represent a promising class of Aβ42-lowering anti-amyloidogenic compounds for the treatment of AD. Gamma-secretase modulators change the relative proportion of secreted Aβ peptides, while sparing the γ-secretase–mediated processing event resulting in the release of the cytoplasmic APP intracellular domain. In this study, we have characterized how GSMs affect the γ-secretase cleavage of three γ-secretase substrates, E-cadherin, ephrin type A receptor 4 (EphA4) and ephrin type B receptor 2 (EphB2), which all are implicated in important contexts of cell signalling. By using a reporter gene assay, we demonstrate that the γ-secretase–dependent generation of EphA4 and EphB2 intracellular domains is unaffected by GSMs. We also show that γ-secretase processing of EphA4 and EphB2 results in the release of several Aβ-like peptides, but that only the production of Aβ-like proteins from EphA4 is modulated by GSMs, but with an order of magnitude lower potency as compared to Aβ modulation. Collectively, these results suggest that GSMs are selective for γ-secretase–mediated Aβ production

The Transiting System GJ1214: High-Precision Defocused Transit Observations and a Search for Evidence of Transit Timing Variation

Aims: We present 11 high-precision photometric transit observations of the transiting super-Earth planet GJ1214b. Combining these data with observations from other authors, we investigate the ephemeris for possible signs of transit timing variations (TTVs) using a Bayesian approach. Methods: The observations were obtained using telescope-defocusing techniques, and achieve a high precision with random errors in the photometry as low as 1mmag per point. To investigate the possibility of TTVs in the light curve, we calculate the overall probability of a TTV signal using Bayesian methods. Results: The observations are used to determine the photometric parameters and the physical properties of the GJ1214 system. Our results are in good agreement with published values. Individual times of mid-transit are measured with uncertainties as low as 10s, allowing us to reduce the uncertainty in the orbital period by a factor of two. Conclusions: A Bayesian analysis reveals that it is highly improbable that the observed transit times is explained by TTV, when compared with the simpler alternative of a linear ephemeris.Comment: Submitted to A&

High-precision photometry by telescope defocussing - VI. WASP-24, WASP-25 and WASP-26

The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013/) under grant agreement nos. 229517 and 268421. This publication was supported by grants NPRP 09-476-1-078 and NPRP X-019-1-006 from Qatar National Research Fund (a member of Qatar Foundation). TCH acknowledges financial support from the Korea Research Council for Fundamental Science and Technology (KRCF) through the Young Research Scientist Fellowship Programme and is supported by the KASI (Korea Astronomy and Space Science Institute) grant 2012-1-410-02/2013-9-400-00. SG, XW and XF acknowledge the support from NSFC under the grant no. 10873031. The research is supported by the ASTERISK project (ASTERoseismic Investigations with SONG and Kepler) funded by the European Research Council (grant agreement no. 267864). DR, YD, AE, FF (ARC), OW (FNRS research fellow) and J Surdej acknowledge support from the Communauté française de Belgique – Actions de recherche concertées – Académie Wallonie-Europe.We present time series photometric observations of 13 transits in the planetary systems WASP-24, WASP-25 and WASP-26. All three systems have orbital obliquity measurements, WASP-24 and WASP-26 have been observed with Spitzer, and WASP-25 was previously comparatively neglected. Our light curves were obtained using the telescope-defocussing method and have scatters of 0.5–1.2 mmag relative to their best-fitting geometric models. We use these data to measure the physical properties and orbital ephemerides of the systems to high precision, finding that our improved measurements are in good agreement with previous studies. High-resolution Lucky Imaging observations of all three targets show no evidence for faint stars close enough to contaminate our photometry. We confirm the eclipsing nature of the star closest to WASP-24 and present the detection of a detached eclipsing binary within 4.25 arcmin of WASP-26.Publisher PDFPeer reviewe

Asteroseismology of solar-type stars with K2

We present the first detections by the NASA K2 Mission of oscillations in solar-type stars, using short-cadence data collected during K2 Campaign\,1 (C1). We understand the asteroseismic detection thresholds for C1-like levels of photometric performance, and we can detect oscillations in subgiants having dominant oscillation frequencies around $1000\,\rm \mu Hz$. Changes to the operation of the fine-guidance sensors are expected to give significant improvements in the high-frequency performance from C3 onwards. A reduction in the excess high-frequency noise by a factor of two-and-a-half in amplitude would bring main-sequence stars with dominant oscillation frequencies as high as ${\simeq 2500}\,\rm \mu Hz$ into play as potential asteroseismic targets for K2.Comment: Accepted for publication in PASP; 16 pages, 2 figure

Kepler White Paper: Asteroseismology of Solar-Like Oscillators in a 2-Wheel Mission

We comment on the potential for continuing asteroseismology of solar-type and red-giant stars in a 2-wheel Kepler Mission. Our main conclusion is that by targeting stars in the ecliptic it should be possible to perform high-quality asteroseismology, as long as favorable scenarios for 2-wheel pointing performance are met. Targeting the ecliptic would potentially facilitate unique science that was not possible in the nominal Mission, notably from the study of clusters that are significantly brighter than those in the Kepler field. Our conclusions are based on predictions of 2-wheel observations made by a space photometry simulator, with information provided by the Kepler Project used as input to describe the degraded pointing scenarios. We find that elevated levels of frequency-dependent noise, consistent with the above scenarios, would have a significant negative impact on our ability to continue asteroseismic studies of solar-like oscillators in the Kepler field. However, the situation may be much more optimistic for observations in the ecliptic, provided that pointing resets of the spacecraft during regular desaturations of the two functioning reaction wheels are accurate at the < 1 arcsec level. This would make it possible to apply a post-hoc analysis that would recover most of the lost photometric precision. Without this post-hoc correction---and the accurate re-pointing it requires---the performance would probably be as poor as in the Kepler-field case. Critical to our conclusions for both fields is the assumed level of pointing noise (in the short-term jitter and the longer-term drift). We suggest that further tests will be needed to clarify our results once more detail and data on the expected pointing performance becomes available, and we offer our assistance in this work.Comment: NASA Kepler Mission White Paper; 10 pages, 2 figure

The discovery of WASP-151b, WASP-153b, WASP-156b: Insights on giant planet migration and the upper boundary of the Neptunian desert

To investigate the origin of the features discovered in the exoplanet population, the knowledge of exoplanets’ mass and radius with a good precision (≲10%) is essential. To achieve this purpose the discovery of transiting exoplanets around bright stars is of prime interest. In this paper, we report the discovery of three transiting exoplanets by the SuperWASP survey and the SOPHIE spectrograph with mass and radius determined with a precision better than 15%. WASP-151b and WASP-153b are two hot Saturns with masses, radii, densities and equilibrium temperatures of 0.31−0.03+0.04 MJ, 1.13−0.03+0.03 RJ,&nbsp;0.22−0.02+0.03 ρJ and 1290−10+20 K, and 0.39−0.02+0.02 MJ, 1.55−0.08+0.10 RJ,&nbsp;0.11−0.02+0.02 ρJ and 1700−40+40 K, respectively. Their host stars are early G type stars (with mag V ~ 13) and their orbital periods are 4.53 and 3.33 days, respectively. WASP-156b is a super-Neptune orbiting a K type star (mag V = 11.6). It has a mass of 0.128−0.009+0.010 MJ, a radius of 0.51−0.02+0.02 RJ, a density of 1.0−0.1+0.1 ρJ, an equilibrium temperature of&nbsp;970−20+30 K and an orbital period of 3.83 days. The radius of WASP-151b appears to be only slightly inflated, while WASP-153b presents a significant radius anomaly compared to a recently published model. WASP-156b, being one of the few well characterized super-Neptunes, will help to constrain the still debated formation of Neptune size planets and the transition between gas and ice giants. The estimates of the age of these three stars confirms an already observed tendency for some stars to have gyrochronological ages significantly lower than their isochronal ages. We propose that high eccentricity migration could partially explain this behavior for stars hosting a short period planet. Finally, these three planets also lie close to (WASP-151b and WASP-153b) or below (WASP-156b) the upper boundary of the Neptunian desert. Their characteristics support that the ultra-violet irradiation plays an important role in this depletion of planets observed in the exoplanet population