ERP evidence suggests executive dysfunction in ecstasy polydrug users

Background: Deficits in executive functions such as access to semantic/long-term memory have been shown in ecstasy users in previous research. Equally, there have been many reports of equivocal findings in this area. The current study sought to further investigate behavioural and electro-physiological measures of this executive function in ecstasy users. Method: Twenty ecstasy–polydrug users, 20 non-ecstasy–polydrug users and 20 drug-naïve controls were recruited. Participants completed background questionnaires about their drug use, sleep quality, fluid intelligence and mood state. Each individual also completed a semantic retrieval task whilst 64 channel Electroencephalography (EEG) measures were recorded. Results: Analysis of Variance (ANOVA) revealed no between-group differences in behavioural performance on the task. Mixed ANOVA on event-related potential (ERP) components P2, N2 and P3 revealed significant between-group differences in the N2 component. Subsequent exploratory univariate ANOVAs on the N2 component revealed marginally significant between-group differences, generally showing greater negativity at occipito-parietal electrodes in ecstasy users compared to drug-naïve controls. Despite absence of behavioural differences, differences in N2 magnitude are evidence of abnormal executive functioning in ecstasy–polydrug users

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16–1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26–2.02) and in studies using PCR (HR 1.40; 95% CI 1.18–1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86–1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

Structural Maintenance of Chromosomes (SMC) Proteins Promote Homolog-Independent Recombination Repair in Meiosis Crucial for Germ Cell Genomic Stability

In meiosis, programmed DNA breaks repaired by homologous recombination (HR) can be processed into inter-homolog crossovers that promote the accurate segregation of chromosomes. In general, more programmed DNA double-strand breaks (DSBs) are formed than the number of inter-homolog crossovers, and the excess DSBs must be repaired to maintain genomic stability. Sister-chromatid (inter-sister) recombination is postulated to be important for the completion of meiotic DSB repair. However, this hypothesis is difficult to test because of limited experimental means to disrupt inter-sister and not inter-homolog HR in meiosis. We find that the conserved Structural Maintenance of Chromosomes (SMC) 5 and 6 proteins in Caenorhabditis elegans are required for the successful completion of meiotic homologous recombination repair, yet they appeared to be dispensable for accurate chromosome segregation in meiosis. Mutations in the smc-5 and smc-6 genes induced chromosome fragments and dismorphology. Chromosome fragments associated with HR defects have only been reported in mutants, which have disrupted inter-homolog crossover. Surprisingly, the smc-5 and smc-6 mutations did not disrupt the formation of chiasmata, the cytologically visible linkages between homologous chromosomes formed from meiotic inter-homolog crossovers. The mutant fragmentation defect appeared to be preferentially enhanced by the disruptions of inter-homolog recombination but not by the disruptions of inter-sister recombination. Based on these findings, we propose that the C. elegans SMC-5/6 proteins are required in meiosis for the processing of homolog-independent, presumably sister-chromatid-mediated, recombination repair. Together, these results demonstrate that the successful completion of homolog-independent recombination is crucial for germ cell genomic stability

Variants of the Matrix Metalloproteinase-2 but not the Matrix Metalloproteinase-9 genes significantly influence functional outcome after stroke

<p>Abstract</p> <p>Background</p> <p>Multiple lines of evidence suggest that genetic factors contribute to stroke recovery. The matrix metalloproteinases -2 (MMP-2) and -9 (MMP-9) are modulators of extracellular matrix components, with important regulatory functions in the Central Nervous System (CNS). Shortly after stroke, MMP-2 and MMP-9 have mainly damaging effects for brain tissue. However, MMPs also have a beneficial activity in angiogenesis and neurovascular remodelling during the delayed neuroinflammatory response phase, thus possibly contributing to stroke functional recovery.</p> <p>Methods</p> <p>In the present study, the role of <it>MMP-2 </it>and <it>MMP-9 </it>genetic variants in stroke recovery was investigated in 546 stroke patients. Functional outcome was assessed three months after a stroke episode using the modified Rankin Scale (mRS), and patients were classified in two groups: good recovery (mRS ≤ 1) or poor recovery (mRS>1). Haplotype tagging single nucleotide polymorphisms (SNPs) in the <it>MMP-2 </it>(N = 21) and <it>MMP-9 </it>(N = 4) genes were genotyped and tested for association with stroke outcome, adjusting for significant non-genetic clinical variables.</p> <p>Results</p> <p>Six SNPs in the <it>MMP-2 </it>gene were significantly associated with stroke outcome (0.0018<<it>P </it>< 0.0415), two of which survived the Bonferroni correction for multiple testing. In the subset of ischemic stroke patients, association of five of these SNPs remained positive (0.0042<<it>P </it>< 0.0306). No significant associations were found for the <it>MMP-9 </it>gene.</p> <p>Conclusions</p> <p>The results presented strongly indicate that <it>MMP-2 </it>genetic variants are an important mediator of functional outcome after stroke.</p

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Oncostatin M Protects Rod and Cone Photoreceptors and Promotes Regeneration of Cone Outer Segment in a Rat Model of Retinal Degeneration

Retinitis pigmentosa (RP) is a group of photoreceptor degenerative disorders that lead to loss of vision. Typically, rod photoreceptors degenerate first, resulting in loss of night and peripheral vision. Secondary cone degeneration eventually affects central vision, leading to total blindness. Previous studies have shown that photoreceptors could be protected from degeneration by exogenous neurotrophic factors, including ciliary neurotrophic factor (CNTF), a member of the IL-6 family of cytokines. Using a transgenic rat model of retinal degeneration (the S334-ter rat), we investigated the effects of Oncostatin M (OSM), another member of the IL-6 family of cytokines, on photoreceptor protection. We found that exogenous OSM protects both rod and cone photoreceptors. In addition, OSM promotes regeneration of cone outer segments in early stages of cone degeneration. Further investigation showed that OSM treatment induces STAT3 phosphorylation in Müller cells but not in photoreceptors, suggesting that OSM not directly acts on photoreceptors and that the protective effects of OSM on photoreceptors are mediated by Müller cells. These findings support the therapeutic strategy using members of IL-6 family of cytokines for retinal degenerative disorders. They also provide evidence that activation of the STAT3 pathway in Müller cells promotes photoreceptor survival. Our work highlights the importance of Müller cell-photoreceptor interaction in the retina, which may serve as a model of glia-neuron interaction in general

UV-luminous, star-forming hosts of z similar to 2 reddened quasars in the Dark Energy Survey

We present the first rest-frame UV population study of 17 heavily reddened, high-luminosity [E(B − V)QSO ≳ 0.5; Lbol > 1046 erg s−1] broad-line quasars at 1.5 < z < 2.7. We combine the first year of deep, optical, ground-based observations from the Dark Energy Survey (DES) with the near-infrared VISTA Hemisphere Survey and UKIDSS Large Area Survey data, from which the reddened quasars were initially identified. We demonstrate that the significant dust reddening towards the quasar in our sample allows host galaxy emission to be detected at the rest-frame UV wavelengths probed by the DES photometry. By exploiting this reddening effect, we disentangle the quasar emission from that of the host galaxy via spectral energy distribution fitting. We find evidence for a relatively unobscured, star-forming host galaxy in at least 10 quasars, with a further three quasars exhibiting emission consistent with either star formation or scattered light. From the rest-frame UV emission, we derive instantaneous, dust-corrected star formation rates (SFRs) in the range 25 < SFRUV < 365 M⊙ yr−1, with an average SFRUV = 130 ± 95 M⊙ yr−1. We find a broad correlation between SFRUV and the bolometric quasar luminosity. Overall, our results show evidence for coeval star formation and black hole accretion occurring in luminous, reddened quasars at the peak epoch of galaxy formation

Strengths and Weaknesses of Immunotherapy for Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of 12 Randomized Controlled Trials

Background: Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs. Methodology and Principal Findings: We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progressionfre

VDES J2325-5229 a z=2.7 gravitationally lensed quasar discovered using morphology independent supervised machine learning

We present the discovery and preliminary characterization of a gravitationally lensed quasar with a source redshift $\textit{zs}$ = 2.74 and image separation of 2.9 arcsec lensed by a foreground $\textit{zl}$ = 0.40 elliptical galaxy. Since optical observations of gravitationally lensed quasars show the lens system as a superposition of multiple point sources and a foreground lensing galaxy, we have developed a morphology-independent multi-wavelength approach to the photometric selection of lensed quasar candidates based on Gaussian Mixture Models (GMM) supervised machine learning. Using this technique and $\textit{gi}$ multicolour photometric observations from the Dark Energy Survey (DES), near-IR $\textit{JK}$ photometry from the VISTA Hemisphere Survey (VHS) and WISE mid-IR photometry, we have identified a candidate system with two catalogue components with $\textit{iAB}$ = 18.61 and $\textit{iAB}$ = 20.44 comprising an elliptical galaxy and two blue point sources. Spectroscopic follow-up with NTT and the use of an archival AAT spectrum show that the point sources can be identified as a lensed quasar with an emission line redshift of $\textit{z}$ = 2.739 ± 0.003 and a foreground early-type galaxy with $\textit{z}$ = 0.400 ± 0.002. We model the system as a single isothermal ellipsoid and find the Einstein radius θE ∼ 1.47 arcsec, enclosed mass $\textit{M}$enc ∼ 4 × 10$^{11}$$\textit{M}$⊙ and a time delay of ∼52 d. The relatively wide separation, month scale time delay duration and high redshift make this an ideal system for constraining the expansion rate beyond a redshift of 1.FO is supported jointly by CAPES (the Science without Borders programme) and the Cambridge Commonwealth Trust. RGM, CAL, MWA, MB, SLR acknowledge the support of UK Science and Technology Research Council (STFC). AJC acknowledges the support of a Raymond and Beverly Sackler visiting fellowship at the Institute of Astronomy. For further information regarding funding please visit the publisher's website