43 research outputs found

    Communication : where evolutionary linguistics went wrong

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    In this article we offer a detailed assessment of current approaches to the origins of language, with a special focus on their historical and theoretical underpinnings. It is a widely accepted view within evolutionary linguistics that an account of the emergence of human language necessarily involves paying special attention to its communicative function and its relation to other animal communication systems. Ever since Darwin, some variant of this view has constituted the mainstream version in evolutionary linguistics; however, it is our contention in this article that this approach is seriously flawed, and that "animal communication" does not constitute a natural kind on which a sound theoretical model can be built. As a consequence, we argue that this communicative perspective is better abandoned in favor of a structural/formal approach based on the notion of homology, and that some interesting and unexpected similarities may be found by applying this venerable comparative method founded in the 19th century by Richard Owen

    Quantitative Computed Tomography in COPD: Possibilities and Limitations

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    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD

    Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

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    The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∌2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts

    Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

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    Correction Volume: 10, Article Number: 2068 DOI: 10.1038/s41467-019-10160-w WOS:000466339700001General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P <5 x 10(-8)) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.Peer reviewe

    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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    This review focuses on the expression and function of muscarinic acetylcholine receptors (mAChRs), α1-adrenoceptors and relaxin receptors in the male reproductive tract. The localization and differential expression of mAChR and α1-adrenoceptor subtypes in specific compartments of the efferent ductules, epididymis, vas deferens, seminal vesicle and prostate of various species indicate a role for these receptors in the modulation of luminal fluid composition and smooth muscle contraction, including effects on male fertility. Furthermore, the activation of mAChRs induces transactivation of the epidermal growth factor receptor (EGFR) and the Sertoli cell proliferation. The relaxin receptors are present in the testis, RXFP1 in elongated spermatids and Sertoli cells from rat, and RXFP2 in Leydig and germ cells from rat and human, suggesting a role for these receptors in the spermatogenic process. The localization of both receptors in the apical portion of epithelial cells and smooth muscle layers of the vas deferens suggests an involvement of these receptors in the contraction and regulation of secretion.Esta revisĂŁo enfatiza a expressĂŁo e a função dos receptores muscarĂ­nicos, adrenoceptores α1 e receptores para relaxina no sistema reprodutor masculino. A expressĂŁo dos receptores muscarĂ­nicos e adrenoceptores α1 em compartimentos especĂ­ficos de dĂșctulos eferentes, epidĂ­dimo, ductos deferentes, vesĂ­cula seminal e prĂłstata de vĂĄrias espĂ©cies indica o envolvimento destes receptores na modulação da composição do fluido luminal e na contração do mĂșsculo liso, incluindo efeitos na fertilidade masculina. AlĂ©m disso, a ativação dos receptores muscarĂ­nicos leva Ă  transativação do receptor para o fator crescimento epidermal e proliferação das cĂ©lulas de Sertoli. Os receptores para relaxina estĂŁo presentes no testĂ­culo, RXFP1 nas espermĂĄtides alongadas e cĂ©lulas de Sertoli de rato e RXFP2 nas cĂ©lulas de Leydig e germinativas de ratos e humano, sugerindo o envolvimento destes receptores no processo espermatogĂȘnico. A localização de ambos os receptores na porção apical das cĂ©lulas epiteliais e no mĂșsculo liso dos ductos deferentes de rato sugere um papel na contração e na regulação da secreção.Fundação de Amparo Ă  Pesquisa do Estado de SĂŁo Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientĂ­fico e TecnolĂłgico (CNPq)Universidade Federal de SĂŁo Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

    Expression and function of G-protein-coupled receptorsin the male reproductive tract

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