Mitochondrial precursor proteins are imported through a hydrophilic membrane environment

We have analyzed how translocation intermediates of imported mitochondrial precursor proteins, which span contact sites, interact with the mitochondrial membranes. F1-ATPase subunit β(F1β) was trapped at contact sites by importing it into Neurospora mitochondria in the presence of low levels of nucleoside triphosphates. This F1β translocation intermediate could be extracted from the membranes by treatment with protein denaturants such as alkaline pH or urea. By performing import at low temperatures, the ADP/ATP carrier was accumulated in contact sites of Neurospora mitochondria and cytochrome b2 in contact sites of yeast mitochondria. These translocation intermediates were also extractable from the membranes at alkaline pH. Thus, translocation of precursor proteins across mitochondrial membranes seems to occur through an environment which is accessible to aqueous perturbants. We propose that proteinaceous structures are essential components of a translocation apparatus present in contact sites

Young people, crime and school exclusion: a case of some surprises

During the 1990s the number of young people being permanently excluded from schools in England and Wales increased dramatically from 2,910 (1990/91) to a peak of 12,700 (1996/97). Coinciding with this rise was a resurgence of the debate centring on lawless and delinquent youth. With the publication of Young People and Crime (Graham and Bowling 1995) and Misspent Youth (Audit Commission 1996) the 'common sense assumption' that exclusion from school inexorably promoted crime received wide support, with the school excludee portrayed as another latter day 'folk devil'. This article explores the link between school exclusion and juvenile crime, and offers some key findings from a research study undertaken with 56 young people who had experience of being excluded from school. Self-report interview questions reveal that whilst 40 of the young people had offended, 90% (36) reported that the onset of their offending commenced prior to their first exclusion. Moreover, 50 (89.2% of the total number of young people in the sample), stated that they were no more likely to offend subsequent to being excluded and 31 (55.4%) stated that they were less likely to offend during their exclusion period. Often, this was because on being excluded, they were 'grounded' by their parents

Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of December 27th, 2004 with the AMANDA-II detector

On December 27th 2004, a giant gamma flare from the Soft Gamma-ray Repeater 1806-20 saturated many satellite gamma-ray detectors. This event was by more than two orders of magnitude the brightest cosmic transient ever observed. If the gamma emission extends up to TeV energies with a hard power law energy spectrum, photo-produced muons could be observed in surface and underground arrays. Moreover, high-energy neutrinos could have been produced during the SGR giant flare if there were substantial baryonic outflow from the magnetar. These high-energy neutrinos would have also produced muons in an underground array. AMANDA-II was used to search for downgoing muons indicative of high-energy gammas and/or neutrinos. The data revealed no significant signal. The upper limit on the gamma flux at 90% CL is dN/dE < 0.05 (0.5) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2). Similarly, we set limits on the normalization constant of the high-energy neutrino emission of 0.4 (6.1) TeV^-1 m^-2 s^-1 for gamma=-1.47 (-2).Comment: 14 pages, 3 figure

Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

International audienceBackground: Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods: A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results: We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions: We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection

A second generation cervico-vaginal lavage device shows similar performance as its preceding version with respect to DNA yield and HPV DNA results

Contains fulltext : 118480.pdf (publisher's version ) (Open Access)BACKGROUND: Attendance rates of cervical screening programs can be increased by offering HPV self-sampling to non-attendees. Acceptability, DNA yield, lavage volumes and choice of hrHPV test can influence effectiveness of the self-sampling procedures and could therefore play a role in recruiting non-attendees. To increase user-friendliness, a frequently used lavage sampler was modified. In this study, we compared this second generation lavage device with the first generation device within similar birth cohorts. METHODS: Within a large self-sampling cohort-study among non-responders of the Dutch cervical screening program, a subset of 2,644 women received a second generation self-sampling lavage device, while 11,977 women, matched for age and ZIP-code, received the first generation model. The second generation device was different in shape, color, lavage volume, and packaging, in comparison to its first generation model. The Cochran's test was used to compare both devices for hrHPV positivity rate and response rate. To correct for possible heterogeneity between age and ZIP codes in both groups the Breslow-Day test of homogeneity was used. A T-test was utilized to compare DNA yields of the obtained material in both groups. RESULTS: Median DNA yields were 90.4 mug/ml (95% CI 83.2-97.5) and 91.1 mug/ml (95% CI 77.8-104.4, p= 0.726) and hrHPV positivity rates were 8.2% and 6.9% (p= 0.419) per sample self-collected by the second - and the first generation of the device (p= 0.726), respectively. In addition, response rates were comparable for the two models (35.4% versus 34.4%, p= 0.654). CONCLUSIONS: Replacing the first generation self-sampling device by an ergonomically improved, second generation device resulted in equal DNA yields, comparable hrHPV positivity rates and similar response rates. Therefore, it can be concluded that the clinical performance of the first and second generation models are similar. Moreover, participation of non-attendees in cervical cancer screening is probably not predominantly determined by the type of self-collection device

Unpacking the relationships between impulsivity, neighborhood disadvantage, and adolescent violence : an application of a neighborhood-based group decomposition

The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 615159 (ERC Consolidator Grant DEPRIVEDHOODS, Socio-spatial inequality, deprived neighbourhoods, and neighbourhood effects); and from the Marie Curie programme under the European Union’s Seventh Framework Programme (FP/2007–2013)/Career Integration Grant no. PCIG10-GA-2011-303728 (CIG Grant NBHCHOICE, Neighbourhood choice, neighbourhood sorting, and neighbourhood effects).Scholars have become increasingly interested in how social environments condition the relationships between individual risk-factors and adolescent behavior. An appreciable portion of this literature is concerned with the relationship between impulsivity and delinquency across neighborhood settings. The present article builds upon this growing body of research by considering the more nuanced pathways through which neighborhood disadvantage shapes the development of impulsivity and provides a situational context for impulsive tendencies to manifest in violent and aggressive behaviors. Using a sample of 12,935 adolescent from the National Longitudinal Study of Adolescent to Adult Health (Add Health) (mean age = 15.3, 51% female; 20% Black, 17% Hispanic), we demonstrate the extent to which variation in the association between impulsivity and delinquency across neighborhoods can be attributed to (1) differences in mean-levels of impulsivity and violence and (2) differences in coefficients across neighborhoods. The results of a series of multivariate regression models indicate that impulsivity is positively associated with self-reported violence, and that this relationship is strongest among youth living in disadvantaged neighborhoods. The moderating effect of neighborhood disadvantage can be attributed primarily to the stronger effect of impulsivity on violence in these areas, while differences in average levels of violence and impulsivity account for a smaller, yet nontrivial portion of the observed relationship. These results indicate that the differential effect of impulsivity on violence can be attributed to both developmental processes that lead to the greater concentration of violent and impulsive adolescents in economically deprived neighborhoods as well as the greater likelihood of impulsive adolescents engaging in violence when they reside in economically disadvantaged communities.Publisher PDFPeer reviewe

Quasi-continuous Interpolation Scheme for Pathways between Distant Configurations

A quasi-continuous interpolation (QCI) scheme is introduced for characterizing physically realistic initial pathways from which to initiate transition state searches and construct kinetic transition networks. Applications are presented for peptides, proteins, and a morphological transformation in an atomic cluster. The first step in each case involves end point alignment, and we describe the use of a shortest augmenting path algorithm for optimizing permutational isomers. The QCI procedure then employs an interpolating potential, which preserves the covalent bonding framework for the biomolecules and includes repulsive terms between unconstrained atoms. This potential is used to identify an interpolating path by minimizing contributions from a connected set of images, including terms corresponding to minima in the interatomic distances between them. This procedure detects unphysical geometries in the line segments between images. The most difficult cases, where linear interpolation would involve chain crossings, are treated by growing the structure an atom at a time using the interpolating potential. To test the QCI procedure, we carry through a series of benchmark calculations where the initial interpolation is coupled to explicit transition state searches to produce complete pathways between specified local minima.This work was supported by the Engineering and Physical Sciences Research Council [grant number EP/H042660/1]This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in the Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review. To access the final edited and published work see http://dx.doi.org/10.1021/ct300483

Indication of Electron Neutrino Appearance from an Accelerator-Produced Off-Axis Muon Neutrino Beam

The T2K experiment observes indications of nu(mu) -> nu(mu) e appearance in data accumulated with 1.43 x 10(20) protons on target. Six events pass all selection criteria at the far detector. In a three-flavor neutrino oscillation scenario with |Delta m(23)(2)| = 2.4 x 10(-3) eV(2), sin(2)2 theta(23) = 1 and sin(2)2 theta(13) = 0, the expected number of such events is 1.5 +/- 0.3(syst). Under this hypothesis, the probability to observe six or more candidate events is 7 x 10(-3), equivalent to 2.5 sigma significance. At 90% C.L., the data are consistent with 0.03(0.04) < sin(2)2 theta(13) < 0.28(0.34) for delta(CP) = 0 and a normal (inverted) hierarchy

First year performance of the IceCube neutrino telescope

The first sensors of the IceCube neutrino observatory were deployed at the South Pole during the austral summer of 2004-2005 and have been producing data since February 2005. One string of 60 sensors buried in the ice and a surface array of eight ice Cherenkov tanks took data until December 2005 when deployment of the next set of strings and tanks began. We have analyzed these data, demonstrating that the performance of the system meets or exceeds design requirements. Times are determined across the whole array to a relative precision of better than 3 ns, allowing reconstruction of muon tracks and light bursts in the ice, of air-showers in the surface array and of events seen in coincidence by surface and deep-ice detectors separated by up to 2.5 km