One of the closest exoplanet pairs to the 3:2 Mean Motion Resonance: K2-19b \& c

The K2 mission has recently begun to discover new and diverse planetary systems. In December 2014 Campaign 1 data from the mission was released, providing high-precision photometry for ~22000 objects over an 80 day timespan. We searched these data with the aim of detecting further important new objects. Our search through two separate pipelines led to the independent discovery of K2-19b \& c, a two-planet system of Neptune sized objects (4.2 and 7.2 $R_\oplus$), orbiting a K dwarf extremely close to the 3:2 mean motion resonance. The two planets each show transits, sometimes simultaneously due to their proximity to resonance and alignment of conjunctions. We obtain further ground based photometry of the larger planet with the NITES telescope, demonstrating the presence of large transit timing variations (TTVs), and use the observed TTVs to place mass constraints on the transiting objects under the hypothesis that the objects are near but not in resonance. We then statistically validate the planets through the \texttt{PASTIS} tool, independently of the TTV analysis.Comment: 18 pages, 10 figures, accepted to A&A, updated to match published versio

Photodynamical mass determination of the multiplanetary system K2-19

K2-19 is the second multiplanetary system discovered with K2 observations. The system is composed of two Neptune size planets close to the 3:2 mean-motion resonance. To better characterize the system we obtained two additional transit observations of K2-19b and five additional radial velocity observations. These were combined with K2 data and fitted simultaneously with the system dynamics (photodynamical model) which increases the precision of the transit time measurements. The higher transit time precision allows us to detect the chopping signal of the dynamic interaction of the planets that in turn permits to uniquely characterize the system. Although the reflex motion of the star was not detected, dynamic modelling of the system allowed us to derive planetary masses of Mb = 44 ± 12  M⊕ and Mc = 15.9 ± 7.0  M⊕ for the inner and the outer planets, respectively, leading to densities close to Uranus. We also show that our method allows the derivation of mass ratios using only the 80 d of observations during the first campaign of K2

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Cholesterol Homeostasis in Two Commonly Used Human Prostate Cancer Cell-Lines, LNCaP and PC-3

BACKGROUND:Recently, there has been renewed interest in the link between cholesterol and prostate cancer. It has been previously reported that in vitro, prostate cancer cells lack sterol-mediated feedback regulation of the major transcription factor in cholesterol homeostasis, sterol-regulatory element binding protein 2 (SREBP-2). This could explain the accumulation of cholesterol observed in clinical prostate cancers. Consequently, perturbed feedback regulation to increased sterol levels has become a pervasive concept in the prostate cancer setting. Here, we aimed to explore this in greater depth. METHODOLOGY/PRINCIPAL FINDINGS:After altering the cellular cholesterol status in LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream effects on promoter activity and expression of SREBP-2 target genes, and functional activity (low-density lipoprotein uptake, cholesterol synthesis). In doing so, we observed that LNCaP and PC-3 cells were sensitive to increased sterol levels. In contrast, lowering cholesterol levels via statin treatment generated a greater response in LNCaP cells than PC-3 cells. This highlighted an important difference between these cell-lines: basal SREBP-2 activity appeared to be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels. CONCLUSION/SIGNIFICANCE:Thus, prostate cancer cells are sensitive to changing sterol levels in vitro, but the extent of this regulation differs between prostate cancer cell-lines. These results shed new light on the regulation of cholesterol metabolism in two commonly used prostate cancer cell-lines, and emphasize the importance of establishing whether or not cholesterol homeostasis is perturbed in prostate cancer in vivo

Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.This study received funding from Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This work was supported by grants from Foundation Fighting Blindness Career Development Award CDGE-0621-0809-RAD (SR), Foundation Fighting Blindness project program award PPA-0123-0841-UCL (SR and SdB), Retinitis Pigmentosa Fighting Blindness, Fight for Sight UK (RP Genome Project GR586), Ghent University Special Research Fund (BOF20/GOA/023) (EDB and BL); EJP RD Solve-RET EJPRD19-234 (EDB, BL, SB, CR, FC, and SR). EDB (1802220N) and BL (1803816N) are FWO Senior Clinical Investigators of the Research Foundation Flanders (FWO). EDB, BL, SB, FC, and SR are members of ERN-EYE (Framework Partnership Agreement No. 739534)

The Tree Biodiversity Network (BIOTREE-NET): prospects for biodiversity research and conservation in the Neotropics

Biodiversity research and conservation efforts in the tropics are hindered by the lack of knowledge of the assemblages found there, with many species undescribed or poorly known. Our initiative, the Tree Biodiversity Network (BIOTREE-NET), aims to address this problem by assembling georeferenced data from a wide range of sources, making these data easily accessible and easily queried, and promoting data sharing. The database (GIVD ID NA-00-002) currently comprises ca. 50,000 tree records of ca. 5,000 species (230 in the IUCN Red List) from \u3e2,000 forest plots in 11 countries. The focus is on trees because of their pivotal role in tropical forest ecosystems (which contain most of the world\u27s biodiversity) in terms of ecosystem function, carbon storage and effects on other species. BIOTREE-NET currently focuses on southern Mexico and Central America, but we aim to expand coverage to other parts of tropical America. The database is relational, comprising 12 linked data tables. We summarise its structure and contents. Key tables contain data on forest plots (including size, location and date(s) sampled), individual trees (including diameter, when available, and both recorded and standardised species name), species (including biological traits of each species) and the researchers who collected the data. Many types of queries are facilitated and species distribution modelling is enabled. Examining the data in BIOTREE-NET to date, we found an uneven distribution of data in space and across biomes, reflecting the general state of knowledge of the tropics. More than 90% of the data were collected since 1990 and plot size varies widely, but with most less than one hectare in size. A wide range of minimum sizes is used to define a \u27tree\u27. The database helps to identify gaps that need filling by further data collection and collation. The data can be publicly accessed through a web application at http://portal.biotreenet.com. Researchers are invited and encouraged to contribute data to BIOTREE-NET

Vibrio cholerae vexH Encodes a Multiple Drug Efflux Pump That Contributes to the Production of Cholera Toxin and the Toxin Co-Regulated Pilus

The resistance-nodulation-division (RND) efflux systems are ubiquitous transporters that function in antimicrobial resistance. Recent studies showed that RND systems were required for virulence factor production in Vibrio cholerae. The V. cholerae genome encodes six RND efflux systems. Three of the RND systems (VexB, VexD, and VexK) were previously shown to be redundant for in vitro resistance to bile acids and detergents. A mutant lacking the VexB, VexD, and VexK RND pumps produced wild-type levels of cholera toxin (CT) and the toxin co-regulated pilus (TCP) and was moderately attenuated for intestinal colonization. In contrast, a RND negative mutant produced significantly reduced amounts of CT and TCP and displayed a severe colonization defect. This suggested that one or more of the three uncharacterized RND efflux systems (i.e. VexF, VexH, and VexM) were required for pathogenesis. In this study, a genetic approach was used to generate a panel of V. cholerae RND efflux pump mutants in order to determine the function of VexH in antimicrobial resistance, virulence factor production, and intestinal colonization. VexH contributed to in vitro antimicrobial resistance and exhibited a broad substrate specificity that was redundant with the VexB, VexD, and VexK RND efflux pumps. These four efflux pumps were responsible for in vitro antimicrobial resistance and were required for virulence factor production and intestinal colonization. Mutation of the VexF and/or VexM efflux pumps did not affect in vitro antimicrobial resistance, but did negatively affect CT and TCP production. Collectively, our results demonstrate that the V. cholerae RND efflux pumps have redundant functions in antimicrobial resistance and virulence factor production. This suggests that the RND efflux systems contribute to V. cholerae pathogenesis by providing the bacterium with protection against antimicrobial compounds that are present in the host and by contributing to the regulated expression of virulence factors