1,411 research outputs found

    Recent data on cellular component turnover: Focus on adaptations to physical exercise

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    Significant progress has expanded our knowledge of the signaling pathways coordinatingmuscle protein turnover during various conditions including exercise. In this manuscript, the multiplemechanisms that govern the turnover of cellular components are reviewed, and their overall rolesin adaptations to exercise training are discussed. Recent studies have highlighted the central role ofthe energy sensor (AMP)-activated protein kinase (AMPK), forkhead box class O subfamily protein(FOXO) transcription factors and the kinase mechanistic (or mammalian) target of rapamycin complex(MTOR) in the regulation of autophagy for organelle maintenance during exercise. A new cellulartrafficking involving the lysosome was also revealed for full activation of MTOR and protein synthesisduring recovery. Other emerging candidates have been found to be relevant in organelle turnover,especially Parkin and the mitochondrial E3 ubiquitin protein ligase (Mul1) pathways for mitochondrialturnover, and the glycerolipids diacylglycerol (DAG) for protein translation and FOXO regulation.Recent experiments with autophagy and mitophagy flux assessment have also provided importantinsights concerning mitochondrial turnover during ageing and chronic exercise. However, data inhumans are often controversial and further investigations are needed to clarify the involvement ofautophagy in exercise performed with additional stresses, such as hypoxia, and to understand theinfluence of exercise modality. Improving our knowledge of these pathways should help developtherapeutic ways to counteract muscle disorders in pathological conditions

    Extinction and dawn of the modern world in the Carnian (Late Triassic)

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    The Carnian Pluvial Episode (Late Triassic) was a time of global environmental changes and possibly substantial coeval volcanism. The extent of the biological turnover in marine and terrestrial ecosystems is not well understood. Here, we present a meta-analysis of fossil data that suggests a substantial reduction in generic and species richness and the disappearance of 33% of marine genera. This crisis triggered major radiations. In the sea, the rise of the first scleractinian reefs and rock-forming calcareous nannofossils points to substantial changes in ocean chemistry. On land, there were major diversifications and originations of conifers, insects, dinosaurs, crocodiles, lizards, turtles, and mammals. Although there is uncertainty on the precise age of some of the recorded biological changes, these observations indicate that the Carnian Pluvial Episode was linked to a major extinction event and might have been the trigger of the spectacular radiation of many key groups that dominate modern ecosystems

    Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

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    The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

    Phylogenetic and Morphologic Analyses of a Coastal Fish Reveals a Marine Biogeographic Break of Terrestrial Origin in the Southern Caribbean

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    Marine allopatric speciation involves interplay between intrinsic organismal properties and extrinsic factors. However, the relative contribution of each depends on the taxon under study and its geographic context. Utilizing sea catfishes in the Cathorops mapale species group, this study tests the hypothesis that both reproductive strategies conferring limited dispersal opportunities and an apparent geomorphologic barrier in the Southern Caribbean have promoted speciation in this group from a little studied area of the world.Mitochondrial gene sequences were obtained from representatives of the Cathorops mapale species group across its distributional range from Colombia to Venezuela. Morphometric and meristic analyses were also done to assess morphologic variation. Along a approximately 2000 km transect, two major lineages, Cathorops sp. and C. mapale, were identified by levels of genetic differentiation, phylogenetic reconstructions, and morphological analyses. The lineages are separated by approximately 150 km at the Santa Marta Massif (SMM) in Colombia. The northward displacement of the SMM into the Caribbean in the early Pleistocene altered the geomorphology of the continental margin, ultimately disrupting the natural habitat of C. mapale. The estimated approximately 0.86 my divergence of the lineages from a common ancestor coincides with the timing of the SMM displacement at approximately 0.78 my.Results presented here support the hypothesis that organismal properties as well as extrinsic factors lead to diversification of the Cathorops mapale group along the northern coast of South America. While a lack of pelagic larval stages and ecological specialization are forces impacting this process, the identification of the SMM as contributing to allopatric speciation in marine organisms adds to the list of recognized barriers in the Caribbean. Comparative examination of additional Southern Caribbean taxa, particularly those with varying life history traits and dispersal capabilities, will determine the extent by which the SMM has influenced marine phylogeography in the region

    Clues from nearby galaxies to a better theory of cosmic evolution

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    The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding universe. But the properties of nearby galaxies that can be observed in greatest detail suggest a still better theory would more rapidly gather matter into galaxies and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur

    Hereditary sensory and autonomic neuropathies: types II, III, and IV

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    The hereditary sensory and autonomic neuropathies (HSAN) encompass a number of inherited disorders that are associated with sensory dysfunction (depressed reflexes, altered pain and temperature perception) and varying degrees of autonomic dysfunction (gastroesophageal reflux, postural hypotention, excessive sweating). Subsequent to the numerical classification of four distinct forms of HSAN that was proposed by Dyck and Ohta, additional entities continue to be described, so that identification and classification are ongoing. As a group, the HSAN are rare diseases that affect both sexes. HSAN III is almost exclusive to individuals of Eastern European Jewish extraction, with incidence of 1 per 3600 live births. Several hundred cases with HSAN IV have been reported. The worldwide prevalence of HSAN type II is very low. This review focuses on the description of three of the disorders, HSAN II through IV, that are characterized by autosomal recessive inheritance and onset at birth. These three forms of HSAN have been the most intensively studied, especially familial dysautonomia (Riley-Day syndrome or HSAN III), which is often used as a prototype for comparison to the other HSAN. Each HSAN disorder is likely caused by different genetic errors that affect specific aspects of small fiber neurodevelopment, which result in variable phenotypic expression. As genetic tests are routinely used for diagnostic confirmation of HSAN III only, other means of differentiating between the disorders is necessary. Diagnosis is based on the clinical features, the degree of both sensory and autonomic dysfunction, and biochemical evaluations, with pathologic examinations serving to further confirm differences. Treatments for all these disorders are supportive

    Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

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    Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

    Like Mother(-in-Law) Like Daughter? Influence of the Older Generation’s Fertility Behaviours on Women’s Desired Family Size in Bihar, India

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    This paper investigates the associations between preferred family size of women in rural Bihar, India and the fertility behaviours of their mother and mother-in-law. Scheduled interviews of 440 pairs of married women aged 16–34 years and their mothers-in-law were conducted in 2011. Preferred family size is first measured by Coombs scale, allowing us to capture latent desired number of children and then categorized into three categories (low, medium and high). Women’s preferred family size is estimated using ordered logistic regression. We find that the family size preferences are not associated with mother’s fertility but with mother’s education. Mother-in-law’s desired number of grandchildren is positively associated with women’s preferred family size. However, when the woman has higher education than her mother-in-law, her preferred family size gets smaller, suggesting that education provides women with greater autonomy in their decision-making on childbearing
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