415 research outputs found

    Impactos ambientales significativos generados por la actividad de la empresa Alpes Chiclayo S.A.C. en la producción de conservas de frijol de palo, distrito de Pacora, Lambayeque, Perú

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    El objetivo del presente trabajo fue evaluar los impactos ambientales significativos generados por la actividad de la empresa Alpes Chiclayo S.A.C. en la producción de conserva de frijol de palo, midiendo las variables ambientales: la calidad del aire para medir NO2, O3, SO2 y H2S de acuerdo a lo contemplado en el D.S. 074-PCM, niveles de ruido en los diferentes puntos de la planta, material particulado midiendo los parámetros MP10 y MP2.5 y la calidad de agua fue determinada por el método de Plasma Inducido Acoplado (ICP). Para evaluar los impactos ambientales se utilizó el método de matrices bidimensionales que plotea acciones versus factores ambientales y utilizando el método de Fisher Davies se calificaron los impactos ambientales negativos en una escala de poco significativo, significativo y muy significativo, severo y critico anteponiendo el signo (-). Para los impactos positivos se antepuso el signo (+). Los resultados del monitoreo realizado utilizando el método de matriz bidimensional determinó que los impactos ambientales generados durante el proceso productivo fueron calificados como poco significativos; los impactos positivos fueron sobre la población, agua, suelo y paisaje. Los impactos negativos fueron sobre el suelo, agua y aire. Se concluyó que para mitigar los impactos ambientales identificados se ha elaborado el Programa de Adecuación y Manejo Ambiental (PAMA) para la empresa, orientado al logro del desarrollo sostenible y al paradigma basura cero con la finalidad de mejorar la calidad de vida de la población y del ambiente

    Friction during earthquakes: 25 years of experimental studies

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    Notas: Export Date: 21 March 2022Dynamic fault strength (rock friction in the broad sense) and its evolution with seismic slip and slip rate are among the most relevant parameters in earthquake mechanics. Given the large slip rate (1 m s-1 on average), displacement (up to tens of meters), effective stress (tens of MPa), typical of seismic faulting at depth, thermo-mechanical effects become outstanding: dynamic fault strength is severely affected by fluid and rock phase changes, extreme grain size reduction, and the production of amorphous and unstable materials in the slipping zone. Here, first we will summarize the most relevant findings about dynamic fault strength during seismic slip mainly obtained thanks to the exploitation of dedicated experimental machines (i.e., rotary shear apparatus). However, the interpretation of this experimental dataset remains debated because of technical limitations which impede us to measure fundamental parameters such as temperature, strain rate, pore fluid pressure and grain size in the slipping zone. Without a sound estimate of these physical parameters, any constitutive law proposed to describe the evolution of dynamic fault strength during simulated seismic slip remains speculative. Then, we will discuss the results of some recent experiments which exploit new technical approaches to overcome the main limitations of the previous studies. The experimental approach, together with field studies of the geometry and architecture of exhumed faults and modelling, remains our most powerful tool to investigate seismic-related deformation mechanisms in both natural and human-induced earthquakes

    Finding answers in lipid profile in COVID-19 patients

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    Introduction: A small percentage of patients will develop a severe form of COVID-19 caused by SARS-CoV-2 infection. Thus, it is important to predict the potential outcomes identifying early markers of poor prognosis. In this context, we evaluated the association of SARS-CoV-2 infection with lipid abnormalities and their role in prognosis. Methods: Single-center, retrospective, observational study of COVID-19 patients admitted from March to October 2020. Clinical and laboratory data, comorbidities, and treatments for COVID-19 were evaluated. Main outcomes including intensive care unit (ICU) admission and mortality were analyzed with a multivariable Cox proportional hazards regression model. Results: We selected 1489 from a total of 2038 consecutive patients with confirmed COVID-19, who had a complete lipid profile before ICU admission. During the follow-up performed in 1109 patients, we observed a decrease in T-c, HDL-c, and LDL-c in 28.6%, 42.9%, and 30.4% of patients, respectively, and an increase in TG in 76.8%. The decrease of both T-c and HDL- c was correlated with a decrease in albumin levels (r = 0.39 and r = 0.37, respectively). Kaplan–Meier survival curves found an increased ICU admission in patients with lower T-c (HR 0.55, CI 0.36–0.86), HDL-c (HR 0.61, CI 0.45–0.84), and LDL-c (HR 0.85, CI 0.74–0.97). Higher values of T-c (HR 0.45, CI 0.36–0.57), HDL-c (HR 0.66, CI 0.54–0.81), and LDL-c (HR 0.86, CI 0.78–0.94) showed a protective effect on mortality. Conclusions: Abnormalities in lipid profile are a frequent complication of SARS-CoV-2 infection and might be related to morbidity and mortalityThis work was supported by the following grants: Proyectos de Investigación en Salud (FIS) PI16-02091 and PI19-00584 (funded by Instituto de Salud Carlos III), TIRONET2-CM, B2017/BMD-3724 (funded by Comunidad de Madrid) and cofinanced by FEDER funds to M.M

    Acid ceramidase improves mitochondrial function and oxidative stress in Niemann-Pick type C disease by repressing STARD1 expression and mitochondrial cholesterol accumulation.

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    Niemann-Pick type C (NPC) disease, a lysosomal storage disorder caused by defective NPC1/NPC2 function, results in the accumulation of cholesterol and glycosphingolipids in lysosomes of affected organs, such as liver and brain. Moreover, increase of mitochondrial cholesterol (mchol) content and impaired mitochondrial function and GSH depletion contribute to NPC disease. However, the underlying mechanism of mchol accumulation in NPC disease remains unknown. As STARD1 is crucial in intramitochondrial cholesterol trafficking and acid ceramidase (ACDase) has been shown to regulate STARD1, we explored the functional relationship between ACDase and STARD1 in NPC disease. Liver and brain of Npc1−/− mice presented a significant increase in mchol levels and STARD1 expression. U18666A, an amphiphilic sterol that inhibits lysosomal cholesterol efflux, increased mchol levels in hepatocytes from Stard1f/f mice but not Stard1ΔHep mice. We dissociate the induction of STARD1 expression from endoplasmic reticulum stress, and establish an inverse relationship between ACDase and STARD1 expression and LRH-1 levels. Hepatocytes from Npc1+/+ mice treated with U18666A exhibited increased mchol accumulation, STARD1 upregulation and decreased ACDase expression, effects that were reversed by cholesterol extraction with 2-hydroxypropyl-β-cyclodextrin. Moreover, transfection of fibroblasts from NPC patients with ACDase, decreased STARD1 expression and mchol accumulation, resulting in increased mitochondrial GSH levels, improved mitochondrial functional performance, decreased oxidative stress and protected NPC fibroblasts against oxidative stress-mediated cell death. Our results demonstrate a cholesterol-dependent inverse relationship between ACDase and STARD1 and provide a novel approach to target the accumulation of cholesterol in mitochondria in NPC disease

    Different Approaches to Analyze Muscle Fat Replacement With Dixon MRI in Pompe Disease

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    Altres ajuts: Asociación Española de Enfermos de Glucogenosis (AEEG)Quantitative MRI is an increasingly used method to monitor disease progression in muscular disorders due to its ability to measure changes in muscle fat content (reported as fat fraction) over a short period. Being able to objectively measure such changes is crucial for the development of new treatments in clinical trials. However, the analysis of the images involved continues to be a daunting task because of the time needed. Whether a more specific analysis selecting individual muscles or a global one analyzing the whole thigh or compartments could be a suitable alternative has only been marginally studied. In our study we compare three methods of analysis of 2-point-dixon images in a cohort of 34 patients with late onset Pompe disease followed over a period of one year. We measured fat fraction on MRIs obtained at baseline and at year 1, and we calculated the increment of fat fraction. We correlated the results obtained with the results of muscle function tests to investigate whether the three methods of analysis were equivalent or not. We observed significant differences between the three methods in the estimation of the fat fraction at both baseline and year 1, but no difference was found in the increment in fat fraction between baseline and year 1. When we correlated the fat fraction obtained with each method and the muscle function tests, we found a significant correlation with most tests in all three methods, although in most comparisons the highest correlation coefficient was found with the analysis of individual muscles. We conclude that the fastest strategy of analysis assessing compartments or the whole thigh could be reliable for certain cohorts of patients where the variable to study is the fat increment. In other sorts of studies, an individual muscle approach seems the most reliable technique

    STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

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    Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

    Primer aislamiento y caracterización de la cepa prototipo del virus SARS-CoV-2 a inicios de la pandemia de la COVID-19 en el Perú

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    Introduction: Currently, infections by the SARS-CoV-2 virus exceed 600 million cases in the world. Objective: Isolation and characterization of the SARS-CoV-2 virus causing COVID-19 at the beginning of the pandemic in Peru. Materials and methods: Twenty nasal and pharyngeal swab samples were isolated SARS-CoV-2 using two cell lines, Vero ATCC CCL-81 and Vero E-6; virus identification was performed by RT-PCR and the onset of cytopathic effect (CPE) was evaluated by indirect immunofluorescence and subsequent identification by genomic sequencing. One of the most widely circulating isolates was selected and named the prototype strain (PE/B.1.1/28549/2020). Then 10 successive passages were performed in Vero ATCC CCL-81 cells to assess mutation dynamics. Results: Results detected 11 virus isolates by cytopathic effect, and subsequently confirmed by RT-PCR and indirect immunofluorescence. Of these, six were sequenced and identified as the lineages B.1, B.1.1, B.1.1.1, and B.1.205 according to the Pango lineage nomenclature. The prototype strain corresponded to lineage B.1.1. The analysis of the strains from the successive passages showed mutations mainly at in the spike (S) protein of the virus without variation in the identity of the lineage. Conclusions: Four lineages were isolated in the Vero ATCC CCL-81 cell line. Subcultures in the same cell line show mutations in the spike protein indicating greater adaptability to the host cell and variation in pathogenicity in vitro, a behavior that allows it to have more survival success.Introducción: Actualmente los contagios por el virus del SARS-CoV-2 supera los 600 millones de casos en el mundo. Objetivo: Aislar y caracterizar el virus SARS-CoV-2 causante de la COVID-19 a inicios de la pandemia en el Perú. Materiales y métodos: Se realizó el aislamiento viral a partir de 20 muestras de hisopado nasal y faríngeo positivas a SARS-CoV-2 por RT-PCR. El aislamiento se realizó en las líneas celulares Vero ATCC CCL-81 y Vero E6, evaluando el efecto citopático, la presencia del virus por RT-PCR, inmunofluorescencia indirecta (IFI) y posterior identificación por secuenciación genómica. Posteriormente, uno de los aislamientos de mayor circulación fue seleccionado y denominado cepa prototipo (PE/B.1.1/28549/2020), realizándose 10 pasajes sucesivos en células Vero ATCC CCL-81 para evaluar la dinámica de mutaciones. Resultados: Se observaron 11 aislamientos de virus por efecto citopático confirmándose por RT-PCR e IFI, de los cuales 6 fueron secuenciados identificándose los linajes B.1, B.1.1, B.1.1.1 y B.1.205, según el comité Pango de los genomas. La cepa prototipo corresponde a la variante B.1.1 y el análisis de las secuencias de los pasajes sucesivos mostró mutaciones a nivel de la proteína de la espiga (S) del virus, sin variación en la identidad del linaje. Conclusiones: Se aislaron 4 linajes en la línea celular Vero ATCC CCL-81. Los subcultivos en la misma línea celular muestran mutaciones en la proteína de la espiga, lo que indica mayor adaptabilidad a la célula hospedera y variación de la patogenicidad in vitro, comportamiento que le permite tener más éxito de supervivencia

    Distribution, Abundance and Molecular Analysis of Genus Barbadocladius Cranston & Krosch (Diptera, Chironomidae) in Tropical, High Altitude Andean Streams and Rivers

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    The distribution of the genus Barbadocladius Cranston & Krosch (Diptera: Chironomidae), previously reported from Chile to Bolivia, has extended northwards. Larvae, pupae and pupal exuviae of this genus have been found in the high mountain tropical streams of Peru to 9°22′56″, but are restricted to very high altitude streams (altitudes over 3,278 m asl) compared to the lower altitude streams (below 1,100 m asl) in which the genus is reported in Chile and Argentina. Based on morphological studies, both described species in the genus, Barbadocladius andinus Cranston & Krosch and Barbadocladius limay Cranston & Krosch, have been found in Peru as pupae or pupal exuviae. Morphological analysis of the larvae and pupae revealed no differences between the two described species from Patagonia and Peru, which are of similar size and with a similar armament of hooklets and spines in pupal tergites and sternites. However, molecular analysis of larvae and pupae revealed that in Peru, there are at least two different evolutionary lines, one distributed widely and another restricted to one site. Phylogenetic analysis (using cox1 mitochondrial sequences) of all available sequences of Barbadocladius shows that the Chilean and Argentinean material differs from that of Peru. Therefore, a total of four molecular segregates are identified, although morphologically, neither larvae nor the pupae may be differentiated

    LPA1 receptor and chronic stress: Effects on behaviour and the genes involved in the hippocampal excitatory/inhibitory balance.

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    The LPA1 receptor, one of the six characterized G protein-coupled receptors (LPA1-6) through which lysophosphatidic acid acts, is likely involved in promoting normal emotional behaviours. Current data suggest that the LPA-LPA1-receptor pathway may be involved in mediating the negative consequences of stress on hippocampal function. However, to date, there is no available information regarding the mechanisms whereby the LPA1 receptor mediates this adaptation. To gain further insight into how the LPA-LPA1 pathway may prevent the negative consequences of chronic stress, we assessed the effects of the continuous delivery of LPA on depressive-like behaviours induced by a chronic restraint stress protocol. Because a proper excitatory/inhibitory balance seems to be key for controlling the stress response system, the gene expression of molecular markers of excitatory and inhibitory neurotransmission was also determined. In addition, the hippocampal expression of mineralocorticoid receptor genes and glucocorticoid receptor genes and proteins as well as plasma corticosterone levels were determined. Contrary to our expectations, the continuous delivery of LPA in chronically stressed animals potentiated rather than inhibited some (e.g., anhedonia, reduced latency to the first immobility period), though not all, behavioural effects of stress. Furthermore, this treatment led to an alteration in the genes coding for proteins involved in the excitatory/inhibitory balance in the ventral hippocampus and to changes in corticosterone levels. In conclusion, the results of this study reinforce the assumption that LPA is involved in emotional regulation, mainly through the LPA1 receptor, and regulates the effects of stress on hippocampal gene expression and hippocampus-dependent behaviour.This study was supported by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación/__(PSI2017-83408-P) to C.P., Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía (SEJ1863 to C.P. and CTS-643 to G.E.-T), Consejería de Salud, Junta de Andalucía, (NICOLÁS MONARDE to G.E-T). Ministerio de Educación, Cultura y Deporte (FPU14/01610 to R.D.M.-F. and intramural funding from the EPFL to C.S

    Evaluación física y clínica de sementales bovinos en dos municipios de la costa chica de Guerrero, México

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    Objective: To evaluate the reproductive physical characteristics and general health of stallions in two municipalities of Costa Chica of Guerrero, Mexico. Design/methodology/approach: The study was carried out in the municipalities of Ometepec and Cuajinicuilapa. Thirty bulls between 2 and 10 years of age were evaluated. In the physical reproductive and clinical examination were performed by direct observation, using ultrasound to evaluate attached reproductive glands and testicular parenchyma. Blood samples were taken to determine the blood profile. Descriptive statistics was used to present the results. Results: The 86% of the bulls had adequate legs and feet as well as preputial length. Scrotal circumference was according to the age and breed of the animals. Testicular defects were showed for 30% of the bulls, the most common was hypoplasia and unilateral tumors of testicular parenchyma and epididymis, as well as calcifications of the testicular parenchyma. The 93% of the bulls had normal accessory genital glands. Clinically 24% of the bulls with signs suggestive of anaplasmosis were found. The 76% of the bulls, apparently healthy, presented monocytosis, thrombocytopenia and anemia. Limitations on study/implications: the lack of knowledge of the producers about the need for a comprehensive evaluation of the bulls allows them to suffer from diseases without receiving any type of treatment, decreasing their reproductive efficiency. Findings/conclusions: Most of the bulls evaluated had the minimum physical characteristics required, although the presence of anemia and respiratory diseases may have an indirect negative impact on the reproductive efficiency of the bulls.Objetivo: Evaluar las características físicas reproductivas y la salud general de los sementales en dos municipios de Costa Chica de Guerrero, México. Diseño/metodología/aproximación: Se evaluaron reproductiva y clínicamente 30 sementales, de entre 2 y 10 años. El examen reproductivo, se realizó por observación directa, empleándose ecografía para evaluar glándulas reproductivas anexas y el parénquima testicular. La evaluación clínica se realizó por medio del examen físico y perfil hemático. Se empleó estadística descriptiva para la presentación de los resultados. Resultados: El 86% de los sementales tuvieron aplomos y largo prepucial adecuado, así como circunferencia escrotal acorde a la edad y raza de los animales. El 30% de los sementales presentaron defectos testiculares, siendo los más comunes, hipoplasia y tumores unilaterales de parénquima testicular y epidídimos, así como calcificaciones del parénquima testicular. El 93% de las glándulas anexas fueron normales. Clínicamente se encontró un 24% de los sementales con signos sugerentes a anaplasmosis. El 76% de los toros, aparentemente sanos, presentaron monocitosis, trombocitopenia y anemia. Limitaciones del estudio/implicaciones: El desconocimiento de los productores sobre la necesidad de una evaluación integral de los sementales permite que éstos padezcan enfermedades que no son tratadas, disminuyendo su eficiencia reproductiva. Hallazgos/conclusiones: La mayoría de los sementales evaluados tuvieron las características físicas mínimas requeridas, aunque la presencia de anemia y enfermedades respiratorias pueden tener incidencia negativa indirecta sobre la eficiencia reproductiva de los sementales
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