466 research outputs found

    Exploitation promotes earlier sex change in a protandrous patellid limpet, Patella aspera Röding, 1798

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    Exploitation of organisms can prompt the reduction in the number and size of target populations consequently affecting reproductive output and replenishment. Here, we investigated the effects of exploitation on the population structure of a protandrous patellid limpet, Patella aspera, an overexploited Macaronesian endemic. Timed dives were used to collect animals across eleven islands of Macaronesia. Individuals were inspected for sex, size, and gonad stage. Using catch effort (time per person) per island coastal perimeter as a surrogate for exploitation intensity, we found that limpet abundance (CPUE) and mean size tended to decrease with exploitation intensity. When considering the sex of animals separately, the size of the largest male, but not females, decreased with exploitation. In contrast, the size of the smallest male remained relatively consistent, whereas the size of the smallest female decreased significantly with exploitation. As exploitation is mostly targeting larger individuals, results suggest that males are compensating the removal of larger females, by undergoing sex change at smaller and presumably earlier sizes. These results have wider implications for the conservation of P. aspera, as a reduction in female size will likely affect the numbers of oocytes produced, hence fecundity. Regulations promoting the protection of the larger-sized animals should be enforced to safeguard the replenishment of the population

    SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

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    SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells

    Non-reducible knee dislocation with interposition of the vastus medialis muscle

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    Irreducibility of the knee following complete dislocation is a rare event determined by the interposition of various capsulo-ligamentous structures in the joint space. Such cases often require urgent surgical treatment. We report the case of a healthy 70-year-old man with a sprain of the left knee that occurred after a sports trauma. The patient showed knee dislocation with multiple ligamentous injuries and articular block due to interposition of a portion of the vastus medialis muscle. After arthroscopic evaluation, we performed surgical treatment to free the muscle, regularize the medial meniscus and suture the posterior and medial capsule and ligaments; the cruciate ligaments were not treated. The most interesting aspect of the articular damage in this case was a wide detachment of the vastus medialis muscle with intra-articular dislocation. The decision to treat only the posterior lesions and allow the healing of the front ones by rehabilitation treatment was supported by full functional recovery and return to sports activity

    Cd44v6 high membranous expression is a predictive marker of therapy response in gastric cancer patients

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    In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and-negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.This work was funded by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 and NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); project POCI-01-0145-FEDER-016390 and SAICTPAC/0022/2015, funded by ERDF, POCI, and FCT; project PTDC/CTM-NAN/120958/2010, from FCT; and by project PTDC/BTM-TEC/30164/2017 funded by ERDF funds through the COMPETE 2020–POCI, Portugal 2020, and by FCT. Salary support to G.M.A. by PTDC/BTM-TEC/30164/2017 project; C.P. was supported by the grant SFRH/BD/113031/2015 from FCT

    Cross-national differences in clinically significant cannabis problems: epidemiologic evidence from 'cannabis-only' smokers in the United States, Mexico, and Colombia

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    <p>Abstract</p> <p>Background</p> <p>Epidemiological studies show wide variability in the occurrence of cannabis smoking and related disorders across countries. This study aims to estimate cross-national variation in cannabis users' experience of clinically significant cannabis-related problems in three countries of the Americas, with a focus on cannabis users who may have tried alcohol or tobacco, but who have not used cocaine, heroin, LSD, or other internationally regulated drugs.</p> <p>Methods</p> <p>Data are from the World Mental Health Surveys Initiative and the National Latino and Asian American Study, with probability samples in Mexico (n = 4426), Colombia (n = 5,782) and the United States (USA; n = 8,228). The samples included 212 'cannabis only' users in Mexico, 260 in Colombia and 1,724 in the USA. Conditional GLM with GEE and 'exact' methods were used to estimate variation in the occurrence of clinically significant problems in cannabis only (CO) users across these surveyed populations.</p> <p>Results</p> <p>The experience of cannabis-related problems was quite infrequent among CO users in these countries, with weighted frequencies ranging from 1% to 5% across survey populations, and with no appreciable cross-national variation in general. CO users in Colombia proved to be an exception. As compared to CO users in the USA, the Colombia smokers were more likely to have experienced cannabis-associated 'social problems' (odds ratio, OR = 3.0; 95% CI = 1.4, 6.3; p = 0.004) and 'legal problems' (OR = 9.7; 95% CI = 2.7, 35.2; p = 0.001).</p> <p>Conclusions</p> <p>This study's most remarkable finding may be the similarity in occurrence of cannabis-related problems in this cross-national comparison within the Americas. Wide cross-national variations in estimated population-level cumulative incidence of cannabis use disorders may be traced to large differences in cannabis smoking prevalence, rather than qualitative differences in cannabis experiences. More research is needed to identify conditions that might make cannabis-related social and legal problems more frequent in Colombia than in the USA.</p

    Glucose Availability and AMP-Activated Protein Kinase Link Energy Metabolism and Innate Immunity in the Bovine Endometrium

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    Defences against the bacteria that usually infect the endometrium of postpartum cattle are impaired when there is metabolic energy stress, leading to endometritis and infertility. The endometrial response to bacteria depends on innate immunity, with recognition of pathogen-associated molecular patterns stimulating inflammation, characterised by secretion of interleukin (IL)-1β, IL-6 and IL-8. How metabolic stress impacts tissue responses to pathogens is unclear, but integration of energy metabolism and innate immunity means that stressing one system might affect the other. Here we tested the hypothesis that homeostatic pathways integrate energy metabolism and innate immunity in bovine endometrial tissue. Glucose deprivation reduced the secretion of IL-1β, IL-6 and IL-8 from ex vivo organ cultures of bovine endometrium challenged with the pathogen-associated molecular patterns lipopolysaccharide and bacterial lipopeptide. Endometrial inflammatory responses to lipopolysaccharide were also reduced by small molecules that activate or inhibit the intracellular sensor of energy, AMP-activated protein kinase (AMPK). However, inhibition of mammalian target of rapamycin, which is a more global metabolic sensor than AMPK, had little effect on inflammation. Similarly, endometrial inflammatory responses to lipopolysaccharide were not affected by insulin-like growth factor-1, which is an endocrine regulator of metabolism. Interestingly, the inflammatory responses to lipopolysaccharide increased endometrial glucose consumption and induced the Warburg effect, which could exacerbate deficits in glucose availability in the tissue. In conclusion, metabolic energy stress perturbed inflammatory responses to pathogen-associated molecular patterns in bovine endometrial tissue, and the most fundamental regulators of cellular energy, glucose availability and AMPK, had the greatest impact on innate immunity
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