Genomic architecture of adaptive radiation and hybridization in Alpine whitefish

Adaptive radiations represent some of the most remarkable explosions of diversification across the tree of life. However, the constraints to rapid diver- sification and how they are sometimes overcome, particularly the relative roles of genetic architecture and hybridization, remain unclear. Here, we address these questions in the Alpine whitefish radiation, using a whole-genome dataset that includes multiple individuals of each of the 22 species belonging to six ecologically distinct ecomorph classes across several lake-systems. We reveal that repeated ecological and morphological diversification along a common environmental axis is associated with both genome-wide allele fre- quency shifts and a specific, larger effect, locus, associated with the gene edar. Additionally, we highlight the possible role of introgression between species from different lake-systems in facilitating the evolution and persistence of species with unique trait combinations and ecology. These results highlight the importance of both genome architecture and secondary contact with hybridization in fuelling adaptive radiation

The role of morphological markedness in the processing of number and gender agreement in Spanish: an event-related potential investigation

Current morphological theory assumes that feature values, such as masculine and feminine or singular and plural, are asymmetrically represented. That is, one member of the opposition (e.g. feminine for gender, plural for number) is assumed to be marked, and the other one, unmarked. The present study examines how these asymmetries impact agreement resolution in Spanish. Agreement was manipulated between a noun acting as head of a relative clause and an adjective located inside the relative clause (e.g. catedral que parecía inmensa “cathedral that looked huge”). Half of the nouns were feminine (marked) and the other half, masculine (unmarked). Half of the nouns were used in the plural (marked) and the other half, in the singular (unmarked). Twenty-seven Spanish native speakers read 240 sentences while their brain activity was recorded with EEG and performed a grammaticality judgment. Results showed that both number and gender violations elicited a central-posterior P600, a component associated with syntactic repair, and a late anterior negativity, argued to reflect working memory costs. Only the P600 was affected by markedness. It started earlier for violations where the mismatching feature was marked. Moreover, it was larger for errors where the mismatching feature was marked, although this amplitude modulation only emerged for number, possibly due to differences in how number and gender cues were realized (i.e. both masculine and feminine showed overt inflection, but singular was uninflected relative to plural). These results suggest that the parser is sensitive to markedness asymmetries in the course of online processing

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

An updated protocol for a systematic review of implementation-related measures

Abstract Background Implementation science is the study of strategies used to integrate evidence-based practices into real-world settings (Eccles and Mittman, Implement Sci. 1(1):1, 2006). Central to the identification of replicable, feasible, and effective implementation strategies is the ability to assess the impact of contextual constructs and intervention characteristics that may influence implementation, but several measurement issues make this work quite difficult. For instance, it is unclear which constructs have no measures and which measures have any evidence of psychometric properties like reliability and validity. As part of a larger set of studies to advance implementation science measurement (Lewis et al., Implement Sci. 10:102, 2015), we will complete systematic reviews of measures that map onto the Consolidated Framework for Implementation Research (Damschroder et al., Implement Sci. 4:50, 2009) and the Implementation Outcomes Framework (Proctor et al., Adm Policy Ment Health. 38(2):65-76, 2011), the protocol for which is described in this manuscript. Methods Our primary databases will be PubMed and Embase. Our search strings will be comprised of five levels: (1) the outcome or construct term; (2) terms for measure; (3) terms for evidence-based practice; (4) terms for implementation; and (5) terms for mental health. Two trained research specialists will independently review all titles and abstracts followed by full-text review for inclusion. The research specialists will then conduct measure-forward searches using the “cited by” function to identify all published empirical studies using each measure. The measure and associated publications will be compiled in a packet for data extraction. Data relevant to our Psychometric and Pragmatic Evidence Rating Scale (PAPERS) will be independently extracted and then rated using a worst score counts methodology reflecting “poor” to “excellent” evidence. Discussion We will build a centralized, accessible, searchable repository through which researchers, practitioners, and other stakeholders can identify psychometrically and pragmatically strong measures of implementation contexts, processes, and outcomes. By facilitating the employment of psychometrically and pragmatically strong measures identified through this systematic review, the repository would enhance the cumulativeness, reproducibility, and applicability of research findings in the rapidly growing field of implementation science

Exome Sequencing Reveals Comprehensive Genomic Alterations across Eight Cancer Cell Lines

It is well established that genomic alterations play an essential role in oncogenesis, disease progression, and response of tumors to therapeutic intervention. The advances of next-generation sequencing technologies (NGS) provide unprecedented capabilities to scan genomes for changes such as mutations, deletions, and alterations of chromosomal copy number. However, the cost of full-genome sequencing still prevents the routine application of NGS in many areas. Capturing and sequencing the coding exons of genes (the “exome”) can be a cost-effective approach for identifying changes that result in alteration of protein sequences. We applied an exome-sequencing technology (Roche Nimblegen capture paired with 454 sequencing) to identify sequence variation and mutations in eight commonly used cancer cell lines from a variety of tissue origins (A2780, A549, Colo205, GTL16, NCI-H661, MDA-MB468, PC3, and RD). We showed that this technology can accurately identify sequence variation, providing ∼95% concordance with Affymetrix SNP Array 6.0 performed on the same cell lines. Furthermore, we detected 19 of the 21 mutations reported in Sanger COSMIC database for these cell lines. We identified an average of 2,779 potential novel sequence variations/mutations per cell line, of which 1,904 were non-synonymous. Many non-synonymous changes were identified in kinases and known cancer-related genes. In addition we confirmed that the read-depth of exome sequence data can be used to estimate high-level gene amplifications and identify homologous deletions. In summary, we demonstrate that exome sequencing can be a reliable and cost-effective way for identifying alterations in cancer genomes, and we have generated a comprehensive catalogue of genomic alterations in coding regions of eight cancer cell lines. These findings could provide important insights into cancer pathways and mechanisms of resistance to anti-cancer therapies

Infinitive Wh-relatives in romance : consequences for the truncation-versus-intervention debate

Romance clitic left dislocation is widespread across all kinds of nonroot contexts, but it is forbidden in infinitive wh-relatives. This article investigates the extent and nature of this restriction and the consequences it raises for the truncation and intervention analyses of the left periphery of embedded sentences. We will show that current proposals cannot account for the whole gamut of data. In consequence, we will propose that infinitive wh-relatives display a maximally syncretic left periphery, whereas infinitive wh-interrogatives have a full-fledged left periphery, crucially involving ForceP, because they are selected by a higher predicate. This crucial difference between infinitive relatives and interrogatives will also be shown to be consistent with the existence of specialized complementizers for the former but not the latte

Resveratrol Inhibits Cancer Cell Metabolism by Down Regulating Pyruvate Kinase M2 via Inhibition of Mammalian Target of Rapamycin

Metabolism of cancer cells with pyruvate kinase M2 (PKM2) at its centre stage has assumed a prime significance in cancer research in recent times. Cancer cell metabolism, characterized by enhanced glucose uptake, production of lactate and anabolism is considered an ideal target for therapeutic interventions. Expression of PKM2 switches metabolism in favor of cancer cells, therefore, the present study was designed to investigate the hitherto unknown effect of resveratrol, a phytoalexin, on PKM2 expression and resultant implications on cancer metabolism. We observed that resveratrol down-regulated PKM2 expression by inhibiting mTOR signaling and suppressed cancer metabolism, adjudged by decreased glucose uptake, lactate production (aerobic glycolysis) and reduced anabolism (macromolecule synthesis) in various cancer cell lines. A contingent decrease in intracellular levels of ribose-5-phosphate (R5P), a critical intermediate of pentose phosphate pathway, accounted for a reduced anabolism. Consequently, the state of suppressed cancer metabolism resulted in decreased cellular proliferation. Interestingly, shRNA-mediated silencing of PKM2 inhibited glucose uptake and lactate production, providing evidence for the critical role of PKM2 and its mediation in the observed effects of resveratrol on cancer metabolism. Further, an over-expression of PKM2 abolished the observed effects of resveratrol, signifying the role of PKM2 downregulation as a critical function of resveratrol. The study reports a novel PKM2-mediated effect of resveratrol on cancer metabolism and provides a new dimension to its therapeutic potential

The application of rules in morphology, syntax and number processing: a case of selective deficit of procedural or executive mechanisms?: Deficit of procedural or executive mechanisms

International audienceDeclarative memory is a long-term store for facts, concepts and words. Procedural memory subserves the learning and control of sensorimotor and cognitive skills, including the mental grammar. In this study, we report a single-case study of a mild aphasic patient who showed procedural deficits in the presence of preserved declarative memory abilities. We administered several experiments to explore rule application in morphology, syntax and number processing. Results partly support the differentiation between declarative and procedural memory. Moreover, the patient's performance varied according to the domain in which rules were to be applied, which underlines the need for more fine-grained distinctions in cognition between procedural rules