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

Usage of FTA (R) Classic Cards for Safe Storage, Shipment, and Detection of Arboviruses

Infections caused by arthropod-borne RNA viruses are overrepresented among emerging infectious diseases. Effective methods for collecting, storing, and transporting clinical or biological specimens are needed worldwide for disease surveillance. However, many tropical regions where these diseases are endemic lack analytical facilities and possibility of continuous cold chains, which presents challenges from both a biosafety and material preservation perspective. Whatman (R) FTA (R) Classic Cards may serve as an effective and safe option for transporting hazardous samples at room temperature, particularly for RNA viruses classified as biosafety level (BSL) 2 and 3 pathogens, from sampling sites to laboratories. In this study, we investigated the biosafety and perseverance of representative alpha-and flaviviruses stored on FTA (R) cards. To evaluate the virus inactivation capacity of FTA (R) cards, we used Sindbis virus (SINV), chikungunya virus (CHIKV), and Japanese encephalitis virus (JEV). We inoculated susceptible cells with dilution series of eluates from viral samples stored on the FTA (R) cards and observed for cytopathic effect to evaluate the ability of the cards to inactivate viruses. All tested viruses were inactivated after storage on FTA (R) cards. In addition, we quantified viral RNA of JEV, SINV, and tick-borne encephalitis virus (TBEV) stored on FTA (R) cards at 4 degrees C, 25 degrees C, and 37 degrees C for 30 days using two reverse transcriptase quantitative PCR assays. Viral RNA of SINV stored on FTA (R) cards was not reduced at either 4 degrees C or 25 degrees C over a 30-day period, but degraded rapidly at 37 degrees C. For JEV and TBEV, degradation was observed at all temperatures, with the most rapid degradation occurring at 37 degrees C. Therefore, the use of FTA (R) cards provides a safe and effective workflow for the collection, storage, and analysis of BSL 2- and 3-virus RNA samples, but there is a risk of false negative results if the cards are stored at higher temperatures for long periods of time. Conscious usage of the cards can be useful in disease surveillance and research, especially in tropical areas where transportation and cold chains are problematic

Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors

Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalälven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalälven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind

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

An ancient extrasolar system with five sub-Earth-size planets

The chemical composition of stars hosting small exoplanets (with radii less than four Earth radii) appears to be more diverse than that of gas-giant hosts, which tend to be metal-rich. This implies that small, including Earth-size, planets may have readily formed at earlier epochs in the Universe's history when metals were more scarce. We report Kepler spacecraft observations of Kepler-444, a metal-poor Sun-like star from the old population of the Galactic thick disk and the host to a compact system of five transiting planets with sizes between those of Mercury and Venus. We validate this system as a true five-planet system orbiting the target star and provide a detailed characterization of its planetary and orbital parameters based on an analysis of the transit photometry. Kepler-444 is the densest star with detected solar-like oscillations. We use asteroseismology to directly measure a precise age of 11.2+/-1.0 Gyr for the host star, indicating that Kepler-444 formed when the Universe was less than 20% of its current age and making it the oldest known system of terrestrial-size planets. We thus show that Earth-size planets have formed throughout most of the Universe's 13.8-billion-year history, leaving open the possibility for the existence of ancient life in the Galaxy. The age of Kepler-444 not only suggests that thick-disk stars were among the hosts to the first Galactic planets, but may also help to pinpoint the beginning of the era of planet formation.Comment: Accepted for publication in ApJ; 42 pages, 10 figures, 4 table

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&

KOI-3158: The oldest known system of terrestrial-size planets

The first discoveries of exoplanets around Sun-like stars have fueled efforts to find ever smaller worlds evocative of Earth and other terrestrial planets in the Solar System. While gas-giant planets appear to form preferentially around metal-rich stars, small planets (with radii less than four Earth radii) can form under a wide range of metallicities. This implies that small, including Earth-size, planets may have readily formed at earlier epochs in the Universe's history when metals were far less abundant. We report Kepler spacecraft observations of KOI-3158, a metal-poor Sun-like star from the old population of the Galactic thick disk, which hosts five planets with sizes between Mercury and Venus. We used asteroseismology to directly measure a precise age of 11.2+/-1.0 Gyr for the host star, indicating that KOI-3158 formed when the Universe was less than 20% of its current age and making it the oldest known system of terrestrial-size planets. We thus show that Earth-size planets have formed throughout most of the Universe's 13.8-billion-year history, providing scope for the existence of ancient life in the Galaxy.Comment: Submitted to EPJ Web of Conferences, to appear in the Proceedings of the 3rd CoRoT Symposium, Kepler KASC7 joint meeting; 4 pages, 1 figur

Ages and fundamental properties of Kepler exoplanet host stars from asteroseismology

We present a study of 33 {\it Kepler} planet-candidate host stars for which asteroseismic observations have sufficiently high signal-to-noise ratio to allow extraction of individual pulsation frequencies. We implement a new Bayesian scheme that is flexible in its input to process individual oscillation frequencies, combinations of them, and average asteroseismic parameters, and derive robust fundamental properties for these targets. Applying this scheme to grids of evolutionary models yields stellar properties with median statistical uncertainties of 1.2\% (radius), 1.7\% (density), 3.3\% (mass), 4.4\% (distance), and 14\% (age), making this the exoplanet host-star sample with the most precise and uniformly determined fundamental parameters to date. We assess the systematics from changes in the solar abundances and mixing-length parameter, showing that they are smaller than the statistical errors. We also determine the stellar properties with three other fitting algorithms and explore the systematics arising from using different evolution and pulsation codes, resulting in 1\% in density and radius, and 2\% and 7\% in mass and age, respectively. We confirm previous findings of the initial helium abundance being a source of systematics comparable to our statistical uncertainties, and discuss future prospects for constraining this parameter by combining asteroseismology and data from space missions. Finally we compare our derived properties with those obtained using the global average asteroseismic observables along with effective temperature and metallicity, finding an excellent level of agreement. Owing to selection effects, our results show that the majority of the high signal-to-noise ratio asteroseismic {\it Kepler} host stars are older than the Sun.Comment: 25 pages, 17 figures, MNRAS accepte

An Introduction to Data Analysis in Asteroseismology

A practical guide is presented to some of the main data analysis concepts and techniques employed contemporarily in the asteroseismic study of stars exhibiting solar-like oscillations. The subjects of digital signal processing and spectral analysis are introduced first. These concern the acquisition of continuous physical signals to be subsequently digitally analyzed. A number of specific concepts and techniques relevant to asteroseismology are then presented as we follow the typical workflow of the data analysis process, namely, the extraction of global asteroseismic parameters and individual mode parameters (also known as peak-bagging) from the oscillation spectrum.Comment: Lecture presented at the IVth Azores International Advanced School in Space Sciences on "Asteroseismology and Exoplanets: Listening to the Stars and Searching for New Worlds" (arXiv:1709.00645), which took place in Horta, Azores Islands, Portugal in July 201