L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer

Background: The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition. Results: L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown. Conclusions: A subset of NSCLCs with vessel tropism and increased metastasis aberrantly expresses L1CAM. L1CAM is a novel prognostic marker for NSCLCs that is upregulated by EMT induction and appears to be instrumental for enhanced cell invasion

Planet Hunters X: Searching for Nearby Neighbors of 75 Planet and Eclipsing Binary Candidates from the K2 Kepler Extended Mission

We present high-resolution observations of a sample of 75 K2 targets from Campaigns 1-3 using speckle interferometry on the Southern Astrophysical Research (SOAR) telescope and adaptive optics (AO) imaging at the Keck II telescope. The median SOAR $I$-band and Keck $K_s$-band detection limits at 1" were $\Delta m_{I}=4.4$~mag and $\Delta m_{K_s}=6.1$~mag, respectively. This sample includes 37 stars likely to host planets, 32 targets likely to be eclipsing binaries (EBs), and 6 other targets previously labeled as likely planetary false positives. We find nine likely physically bound companion stars within 3" of three candidate transiting exoplanet host stars and six likely EBs. Six of the nine detected companions are new discoveries; one of the six, EPIC 206061524, is associated with a planet candidate. Among the EB candidates, companions were only found near the shortest period ones ($P<3$ days), which is in line with previous results showing high multiplicity near short-period binary stars. This high-resolution data, including both the detected companions and the limits on potential unseen companions, will be useful in future planet vetting and stellar multiplicity rate studies for planets and binaries.Comment: Accepted in A

Trim17, novel E3 ubiquitin-ligase, initiates neuronal apoptosis

Accumulating data indicate that the ubiquitin-proteasome system controls apoptosis by regulating the level and the function of key regulatory proteins. In this study, we identified Trim17, a member of the TRIM/RBCC protein family, as one of the critical E3 ubiquitin ligases involved in the control of neuronal apoptosis upstream of mitochondria. We show that expression of Trim17 is increased both at the mRNA and protein level in several in vitro models of transcription-dependent neuronal apoptosis. Expression of Trim17 is controlled by the PI3K/Akt/GSK3 pathway in cerebellar granule neurons (CGN). Moreover, the Trim17 protein is expressed in vivo, in apoptotic neurons that naturally die during post-natal cerebellar development. Overexpression of active Trim17 in primary CGN was sufficient to induce the intrinsic pathway of apoptosis in survival conditions. This pro-apoptotic effect was abolished in Bax(-/-) neurons and depended on the E3 activity of Trim17 conferred by its RING domain. Furthermore, knock-down of endogenous Trim17 and overexpression of dominant-negative mutants of Trim17 blocked trophic factor withdrawal-induced apoptosis both in CGN and in sympathetic neurons. Collectively, our data are the first to assign a cellular function to Trim17 by showing that its E3 activity is both necessary and sufficient for the initiation of neuronal apoptosis. Cell Death and Differentiation (2010) 17, 1928-1941; doi: 10.1038/cdd.2010.73; published online 18 June 201

Narrative review of methods and findings of recent studies on the carriage of meningococci and other Neisseria species in the African Meningitis Belt.

OBJECTIVE: To review the findings of studies of pharyngeal carriage of Neisseria meningitidis and related species conducted in the African meningitis belt since a previous review published in 2007. METHODS: PubMed and Web of Science were searched in July 2018 using the terms 'meningococcal OR Neisseria meningitidis OR lactamica AND carriage AND Africa', with the search limited to papers published on or after 1st January 2007. We conducted a narrative review of these publications. RESULTS: One hundred and thirteen papers were identified using the search terms described above, 20 of which reported new data from surveys conducted in an African meningitis belt country. These papers described 40 surveys conducted before the introduction of the group A meningococcal conjugate vaccine (MenAfriVacR ) during which 66 707 pharyngeal swabs were obtained. Carriage prevalence of N. meningitidis varied substantially by time and place, ranging from <1% to 24%. The mean pharyngeal carriage prevalence of N. meningitidis across all surveys was 4.5% [95% CI: 3.4%, 6.8%] and that of capsulated N. meningitidis was 2.8% [95% CI: 1.9%; 5.2%]. A study of households provided strong evidence for meningococcal transmission within and outside households. The introduction of MenAfriVac® led to marked reductions in carriage of the serogroup A meningococcus in Burkina Faso and Chad. CONCLUSIONS: Recent studies employing standardised methods confirm the findings of older studies that carriage of N. meningitidis in the African meningitis belt is highly variable over time and place, but generally occurs with a lower prevalence and shorter duration than reported from industrialised countries

Phenology of the avian spring migratory passage in Europe and North America : Asymmetric advancement in time and increase in duration

Climate change has been shown to shift the seasonal timing (i.e. phenology) and distribution of species. The phenological effects of climate change on living organisms have often been tested using first occurrence dates, which may be uninformative and biased. More rarely investigated is how different phases of a phenological sequence (e.g. beginning, central tendency and end) or its duration have changed over time. This type of analysis requires continuous observation throughout the phenological event over multiple years, and such data sets are rare. In this study we examined the impact of temperature on long-term change of passage timing and duration of the spring migration period in birds, and which species' traits explain species-specific variation. Data used covered 195 species from 21 European and Canadian bird observatories from which systematic daily sampling protocols were available. Migration dates were negatively associated with early spring temperature and timings had in general advanced in 57 years. Short-distance migrants advanced the beginning of their migration more than long-distance migrants when corrected for phylogenic relatedness, but such a difference was not found in other phases of migration. The advancement of migration has generally been greater for the beginning and median phases of migration relative to the end, leading to extended spring migration seasons. Duration of the migration season increased with increasing temperature. Phenological changes have also been less noticeable in Canada even when corrected for rate of change in temperature. To visualize long-term changes in phenology, we constructed the first multi-species spring migration phenology indicator to describe general changes in median migration dates in the northern hemisphere. The indicator showed an average advancement of one week during five decades across the continents (period 1959-2015). The indicator is easy to update with new data and we therefore encourage future research to investigate whether the trend towards longer periods of occurrence or emergence in spring is also evident in other migratory populations. Such phenological changes may influence detectability in monitoring schemes, and may have broader implications on population and community dynamics.Peer reviewe

ProCOC: The prostate cancer outcomes cohort study

BACKGROUND: Despite intensive research over the last several decades on prostate cancer, many questions particularly those concerning early diagnosis and the choice of optimal treatment for each individual patient, still remain unanswered. The goal of treating patients with localized prostate cancer is a curative one and includes minimizing adverse effects to preserve an adequate quality of life. Better understanding on how the quality of life is affected depending on the treatment modality would assist patients in deciding which treatment to choose; furthermore, the development of prognostic biomarkers that indicate the future course of the illness is a promising approach with potential and the focus of much attention. These questions can be addressed in the context of a cohort study. METHODS/DESIGN: This is a prospective, multi-center cohort study within the canton of Zurich, Switzerland. We will include patients with newly diagnosed localized prostate cancer independently of treatment finally chosen. We will acquire clinical data including quality of life and lifestyle, prostate tissue specimen as well as further biological samples (blood and urine) before, during and after treatment for setup of a bio-bank. Assessment of these data and samples in the follow up will be done during routine controls. Study duration will be at least ten years. Influence of treatment on morbidity and mortality, including changes in quality of life, will be identified and an evaluation of biomarkers will be performed. Further we intend to set up a bio-bank containing blood and urine samples providing research of various natures around prostate cancer in the future. DISCUSSION: We presume that this study will provide answers to pertinent questions concerning prognosis and outcomes of men with localised prostate cancer

Pharyngeal carriage of Neisseria species in the African meningitis belt.

OBJECTIVES: Neisseria meningitidis, together with the non-pathogenic Neisseria species (NPNs), are members of the complex microbiota of the human pharynx. This paper investigates the influence of NPNs on the epidemiology of meningococcal infection. METHODS: Neisseria isolates were collected during 18 surveys conducted in six countries in the African meningitis belt between 2010 and 2012 and characterized at the rplF locus to determine species and at the variable region of the fetA antigen gene. Prevalence and risk factors for carriage were analyzed. RESULTS: A total of 4694 isolates of Neisseria were obtained from 46,034 pharyngeal swabs, a carriage prevalence of 10.2% (95% CI, 9.8-10.5). Five Neisseria species were identified, the most prevalent NPN being Neisseria lactamica. Six hundred and thirty-six combinations of rplF/fetA_VR alleles were identified, each defined as a Neisseria strain type. There was an inverse relationship between carriage of N. meningitidis and of NPNs by age group, gender and season, whereas carriage of both N. meningitidis and NPNs was negatively associated with a recent history of meningococcal vaccination. CONCLUSION: Variations in the prevalence of NPNs by time, place and genetic type may contribute to the particular epidemiology of meningococcal disease in the African meningitis belt.MenAfriCar was funded by the Wellcome Trust (086546/Z/08/Z) and the Bill and Melinda Gates Foundation (51251). Kanny Diallo holds a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/j.jinf.2016.03.01

Cosmological parameters constraints from galaxy cluster mass function measurements in combination with other cosmological data

We present the cosmological parameters constraints obtained from the combination of galaxy cluster mass function measurements (Vikhlinin et al., 2009a,b) with new cosmological data obtained during last three years: updated measurements of cosmic microwave background anisotropy with Wilkinson Microwave Anisotropy Probe (WMAP) observatory, and at smaller angular scales with South Pole Telescope (SPT), new Hubble constant measurements, baryon acoustic oscillations and supernovae Type Ia observations. New constraints on total neutrino mass and effective number of neutrino species are obtained. In models with free number of massive neutrinos the constraints on these parameters are notably less strong, and all considered cosmological data are consistent with non-zero total neutrino mass \Sigma m_\nu \approx 0.4 eV and larger than standard effective number of neutrino species, N_eff \approx 4. These constraints are compared to the results of neutrino oscillations searches at short baselines. The updated dark energy equation of state parameters constraints are presented. We show that taking in account systematic uncertainties, current cluster mass function data provide similarly powerful constraints on dark energy equation of state, as compared to the constraints from supernovae Type Ia observations.Comment: Accepted for publication in Astronomy Letter

Large-scale magnetic fields from inflation due to a CPTCPT-even Chern-Simons-like term with Kalb-Ramond and scalar fields

We investigate the generation of large-scale magnetic fields due to the breaking of the conformal invariance in the electromagnetic field through the $CPT$-even dimension-six Chern-Simons-like effective interaction with a fermion current by taking account of the dynamical Kalb-Ramond and scalar fields in inflationary cosmology. It is explicitly demonstrated that the magnetic fields on 1Mpc scale with the field strength of $\sim 10^{-9}$G at the present time can be induced.Comment: 18 pages, 6 figures, version accepted for publication in Eur. Phys. J.