Role of arginase 2 in systemic metabolic activity and adipose tissue fatty acid metabolism in diet-induced obese mice

Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(−/−) or A1(+/−) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2−/−, but not A1+/−, mice. Additionally, A2−/− HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction

Combination of Spatial and Temporal Diversification in European Cropping Systems

There is a lack of results on the advantages and limitations of combining different crop diversification strategies both in time and space, which makes it difficult for famers and advisers to find relevant information for the transition towards more diversified cropping systems. A network of ten field experiments (diverIMPACTS project) was built across seven European countries, covering a range of pedo-climatic conditions and different farming systems: arable and vegetable systems under both conventional and organic management. Each field experiment tests one or several diversified cropping systems, which combine three diversification strategies with low input practices. These diversified cropping systems are compared to reference systems, which are less diversified and more dependent on external inputs. The three strategies of crop diversification are rotation, multiple cropping (growing different crop species on the same land within one growing season) and intercropping (growing different species in proximity on the same field). A diversified system includes, for example, the addition of cover crops or cash crops, such as legumes, for their expected ecosystem services, or crops for new markets (e.g hemp, lentil), the use of multiple cropping to increase productivity per year (e.g. winter barley with soybean) and intercropping (e.g. barley/pea,wheat/faba bean, oat/lupin) to increase productivity per unit of area and reduce external inputs. Expected impacts include: higher arable land productivity, diversification and increased farmer revenues through access to new markets and reduced economic risk, lower environmental impact through reduced use of pesticides, chemical fertilisers, energy and water, and improved delivery of ecosystem services, including biodiversity. The diversified cropping systems will be assessed using standardized measurements across the network and multi-criteria assessment tools. Decisions regarding the design and management of the diversified cropping systems will be recorded to support other diversification initiatives. The year 2018 is the first year of the network. This paper presents the original approach, the strategies designed in the network, and the assumptions concerning the interests to combine temporal and spatial diversification in order to improve the delivery of multiple services. This network will be a source of inspiration for other initiatives of crop diversification in Europe. The ultimate goal is to guide farmers in their transition towards more diversified cropping systems and to promote innovations by various actors at different scales (e.g. innovations regarding machinery for sowing or harvesting new sole or mixed crops, value-chains through the consolidation of new markets, new process of transformation, or adaptation of value-chains to intercropping)

Vasa Nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers

INTRODUCTION The vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. AIM To characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation. MAIN OUTCOME MEASURES Characterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels. METHODS MPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope. RESULTS The neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31-positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra-capsular arterioles and venules, but not the capillaries were innervated by nNOS-positive nerve fibers. CONCLUSIONS This study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels. Beetson KA, Smith SF, Muneer A, Cameron NE, Cotter MA, and Cellek S. Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers. J Sex Med **;**:**-**

Visualization tools for spatio-temporal time-series analysis with context awareness: Montreal subway case

TRANSITDATA 2019 - 5th International Workshop and Symposium, Paris, FRANCE, 08-/07/2019 - 10/07/2019Forecasting passenger demand is of great interest for public transport operators. Despite the important role that forecasting play in mobility demand understanding, in-depth transport oriented analysis of the forecasting results is often overlooked, since it raised some challenges. In this context we developed two visualization tools with open source frameworks that allow to analyze spatio-temporal time-series forecasting with context awareness. The first visualization tool allows to analyze the forecasting results over large period in all the stations and to zoom in for more precise temporal details. The other tool allows to better understand the passenger demand relations between the different stations of the transport network, and enable a spatial analysis of the results. Analyzed time-series corresponds to the forecast results of the number of passengers entering each station with a fine-grained temporal resolution (15 minutes interval) during one year achieved with a well-known machine learning model, a Random Forest. In order to highlight the spatio-temporal specificity of the passenger demand, we have computed and analyzed the residuals of a long-term forecast model that returns normal passenger demand. Here we show that both visualization tools depict the stations and the period hard to predict and allow to have an insight on which contextual element (weather, event on the city and incident on the transport network) could impact the forecasting. Experiment are performed with real data given by the transport authority of Montreal (Société de transport de Montreal, STM)

Efecto del concreto reciclado para mejorar las propiedades de la subrasante en la avenida Álamos, Jayllihuaya, Puno 2021

La presente investigación titulada “Efectos del concreto reciclado para mejorar las propiedades de la subrasante en la avenida Álamos, Jayllihuaya, Puno 2021” se realizó con el objetivo de determinar los efectos del concreto reciclado en las propiedades de la subrasante de la avenida Álamos. La metodología fue de tipo aplicada, enfoque cuantitativo, diseño experimental - cuasi experimental, nivel descriptivo - explicativo, población la avenida Álamos de un 1 km de longitud, la muestra es de 1 km en la cual se realizaron 5 calicatas. Los resultados alcanzados en la investigación muestran que la avenida Álamos presenta una subrasante pobre según la Norma del M.T.C sección Suelo y Geotecnia y Pavimentos. Los resultados reflejan que al incorporar concreto reciclado en las proporciones 5%, 15% y 25% se observa que mejora el I.P pasando de 21.40 a 12.00, también se nota que el O.C.H disminuye de 17.08% a 14.62% y la M.D.S aumenta de 1.720 gr/cm3 a 1.900 gr/cm3 y final mete el C.B.R aumenta de 3.60% a 23.90%. Por consiguiente podemos concluir que la incorporación de concreto reciclado si influye de manera positiva en la subrasante siendo la dosificación optima la de 25%

Influencia de especies de Trichoderma spp. en el control de Botrytis fabae y su mejora en el rendimiento del cultivo de haba (Vicia faba L.) en el distrito de Chucuito - Puno

El cultivo de haba (Vicia faba L.) es importante económicamente para los productores de Puno y es una buena fuente de alimentación y de comercio para la población andina; sin embargo, el rendimiento es bajo debido a las plagas y enfermedades que afectan la producción de granos; entre las enfermedades es muy importante la “mancha chocolate” Botrytis fabae, existiendo gran interés científico en su control biológico; por tal motivo se realizó el presente trabajo de investigación con el objetivo de determinar la influencia de especies de Trichoderma spp. en su bio-control y mejora del rendimiento del cultivo. La investigación se desarrolló en el distrito de Chucuito-Puno, durante los meses de noviembre a mayo 2017 - 2018, el experimento se condujo con un diseño de Bloques Completos al Azar en parcelas divididas con un arreglo factorial 3X4 con tres repeticiones. Se realizaron cuatro aplicaciones foliares, a partir de los primeros síntomas de la enfermedad en las plantas. En Laboratorio, se determinó el área bajo la curva del progreso de la enfermedad (AUDPC) con tres evaluaciones de severidad, realizando pruebas de antibiosis y micoparasitismo in vitro, con la producción de metabolitos solubles inhibitorios por los antagonistas y enfrentamiento dual del patógeno, permitiéndose evaluar la inhibición del crecimiento micelial del patógeno y el porcentaje de colonización del hongo antagónico respectivamente. Se determinó que la cepa Trichoderma nativa obtuvo mayor inhibición micelial del patógeno (50.96%), seguido de T. harzianum y T. viride con 43.59 y 40.39 % respectivamente. Se encontró también que las tres cepas de Trichoderma spp. resultaron ser micoparasitos agresivos, que colonizaron completamente al patógeno. En el ensayo de campo, los tratamientos con aplicaciones de Trichoderma nativo presentaron los valores más altos en la evaluación de características morfológicas; pero, los tratamientos con concentraciones (1x108ufc y 1x107ufc) fueron menos afectados por mancha chocolate con valores de AUDPC de 32.44 y 41.22 respectivamente, frente al testigo T (AUDPC = 166.56). Se obtuvo el mayor rendimiento con la dosis 1x107ufc de 8,956kg/ha, en cambio con la dosis 1x108ufc, solamente 8,489 kg/ha.Tesi

Biochemical and functional studies of twenty sildenafil analogues in human platelets and in the rabbit corpus cavernosum and aorta

Orientador: Gilberto de NucciTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: O sildenafil, inibidor específico de PDE5, é utilizado no tratamento da disfunção erétil. Na procura de um inibidor mais potente e seletivo de PDE5, testamos vinte novos análogos do sildenafil (6a-v), caracterizados pela presença de um grupo sulfonil ou de um substituinte n'n'etilendiamina na posição do grupo metil da piperazina. Os objetivos deste trabalho foram: 1) Avaliar a atividade inibitória da PDE5 de plaquetas humanas; 2) Avaliar o efeito relaxante dos análogos do sildenafil em corpo cavernoso de coelho; 3) Avaliar o efeito relaxante dos análogos do sildenafil em anéis de aorta de coelho. Foi utilizado sangue de voluntários sadios para a atividade inibitória da PDE5 e coelhos New Zealand machos (2-3 kg) procedentes do CEMIB-UNICAMP para os estudos funcionais. Os animais foram anestesiados com uretana, o corpo cavernoso e a artéria aorta foram rapidamente removidos. O tecido cavernoso e anéis de aorta foram montados em banho para órgão isolado contendo solução de Krebs (37oC, 95% O2 / 5% CO2). Os tecidos foram ligados a transdutores isométricos conectados a um sistema PowerLab® de aquisição de dados. Nossos resultados mostraram que a atividade inibitória da PDE5 induzida pelos análogos do sildenafil em plaquetas humanas foi de maneira dependente da concentração. Os compostos 6m, 6n e 6q mostraram valores elevados de IC50 para inibir a PDE5 plaquetária, enquanto que os compostos 6a, 6b, 6d, 6g e 6p produziram inibição inferior a 50%. A potência inibitória (IC50) dos compostos 6c, 6e, 6f, 6h, 6i, 6l e 6o foi similar ao sildenafil (IC50: 0,05 µM) com valores variando entre 0,05 e 0,15 µM. Os análogos que derivaram da molécula n'n'etilendiamina (6r, 6s, 6t e 6v) mostraram uma boa atividade inibitória com valores entre 0,20-0,51 µM. Interessantemente, o composto 6u mostrou uma potência de 0,04 µM, o qual representou o menor valor obtido dos análogos do sildenafil. Nos estudos funcionais, todos os análogos do sildenafil, à exceção do análogo 6m, relaxaram preparações de corpo cavernoso de coelho de maneira dependente da concentração. Particularmente, o análogo 6f mostrou o melhor perfil farmacológico no relaxamento, com potência similar ao sildenafil, e pode servir de base para o desenvolvimento de novos inibidores de PDE5 para o tratamento da disfunção erétil. Além disso, nossos resultados mostraram que os análogos do sildenafil produzem relaxamento dependente da concentração em anéis de aorta de coelho com endotélio íntegro ou removido. Somente o análogo 6b e 6m apresentaram valores de potência inferiores quando comparados ao sildenafil em tecidos com endotélio íntegro. A remoção do endotélio ou a adição do LNAME ou do ODQ (inibidor da NO sintase e da guanilil ciclase solúvel, respectivamente) em tecidos com endotélio íntegro, provocou deslocamento à direita para o sildenafil e seus análogos, à exceção do 6r e 6u que não apresentaram diminuição da potência decorrente da inibição do NO, seja pela remoção do endotélio, pela inibição da NO sintase ou pela inibição da guanilil ciclase solúvel. Nossos dados também mostram que o 6r e 6u, em combinação com o BAY 41-2272, aumentam a potência evocada por estes análogos tanto em anéis de aorta com endotélio íntegro ou removido. O relaxamento evocado pelo sildenafil, 6r e 6u não envolve a participação de canais de potássio e de cálcio, nem envolve a formação de prostanóides. As respostas relaxantes destes dois análogos não foram alteradas em tecidos desprovidos de endotélio, mostrando-se independentes da via NO/GMPc. Isto sugere que estes dois análogos podem ser de particular interesse em patologias decorrentes de disfunção endotelial.Abstract: Sildenafil, a cGMP-specific phosphodiesterase-5 (PDE5) inhibitor, is used for the treatment of erectile dysfunction. In the search for a potent and selective PDE5 inhibitor, new sildenafil analogues (6a-v), characterized by the presence on the sulphonyl group in the 5' position of novel N-4-substituted piperazines or ethylenediamine moiety, were synthesized. The aim of this work was 1) To evaluate the PDE5 inhibitory activity in human platelets; 2) To evaluate the relaxing effect of sildenafil analogues in rabbit corpus cavernosum; 3) To evaluate the relaxing effect of sildenafil analogues in rabbit isolated aorta. Blood from human volunteers were collected and used for PDE5 inhibitory activity and Male New Zealand rabbit (2-3 kg) for functional studies. The rabbits were anaesthetized with urethane and sacrificed. The cavernosal tissue and aortic rings were mounted in organ bath containing Krebs solution (37oC, 95% O2 / 5% CO2). Each tissue was connected to an isometric transducer which was connected to a data acquisition system Powerlab®. Our results showed that sildenafil and its analogues concentration-dependently inhibited PDE5 activity in human platelets. Compounds 6m, 6n and 6q showed higher values of IC50 to inhibit PDE5 of platelets, whereas compounds 6a, 6b, 6d, 6g and 6p did not reach 50% of inhibition. The inhibitory potency of PDE5 for 6c, 6e, 6f, 6h, 6i, 6l and 6o were similar with sildenafil (IC50: 0,05 µM) with values between 0,05-0,15 µM. Derived analogues from n'n' substitution showed great PDE5 inhibitory activity. Interesting, compound 6u exhibited greater IC50 value (0,04 µM). In functional studies, all sildenafil analogues with exception of 6m, relaxed concentration-dependently rabbit corpus cavernosum. Compound 6f exhibited great pEC50 value in corpus cavernosum and could be used as base for developing new PDE5 inhibitors. Moreover, our results showed that sildenafil analogues concentration-dependently relaxed both endothelium-intact and - denuded aortic rings with similar potency values of sildenafil. Compounds 6b and 6m showed lower values of potency when compared to sildenafil in endothelium intact. Endothelium denudation or addition of L-NAME or ODQ (NOS and sGC inhibitors, respectively) caused marked rightward shifts in the curve to sildenafil and its analogues, whereas the relaxation curves for 6r and 6u were not altered after endothelium removal or either by the NO synthase or sGC inhibition. Moreover, our data also suggest that compound 6r and 6u increased the potency values in combination with BAY 41-2272 in both intact and denuded endothelium. The relaxation evoked by sildenafil, 6r and 6u does not involve either calcium or potassium channels or prostanoids formation. The relaxing responses by these compounds were independent of NO/cGMP pathway, suggesting that these compounds may be used in several diseases involving endothelium dysfunction.DoutoradoDoutor em Farmacologi

Análisis del pago del impuesto al patrimonio vehicular y su repercusión en la recaudación de los ingresos de la Municipalidad Provincial de San Román - Juliaca, 2017-2018

La investigación tiene su ámbito de estudio en la Municipalidad de San Román – Juliaca – Gerencia de Administración Tributaria, El cual como objetivo general fue: Determinar las causas del Incumplimiento del pago del Impuesto al Patrimonio Vehicular y su repercusión en la Recaudación de la Municipalidad Provincial de San Román – Juliaca, 2017-2018. Se utilizó la siguiente metodología: Analítico y descriptivo, el tipo de investigación es Descriptivo, nivel basica, enfoque de la investigación es cuantitativo y su diseño es no experimental. Las técnicas que se utilizan son la observación, análisis documental, Encuesta y el instrumento es el cuestionario. La población fue 10, 540 contribuyentes el 2017 y 11,675 el 2018, con una Muestra de 197 contribuyentes. La Conclusión principal fue que, el 54% y el 12% de los contribuyentes indica que adquirieron su unidad Vehicular mediante un Préstamo bancario o Familiar, por lo que se evidencia que no tienen capacidad económica acudiendo a un préstamo porque no cuenta con recursos propios, de igual manera el hecho de tener una formación Educativa aceptable, recibir información tributaria y saber que tiene que pagar impuestos no significa que influya en el cumplimiento del Pago del IPV es indispensable promover la Cultura tributaria. También se concluye que el nivel de recaudación del Impuesto al Patrimonio Vehicular ha sido bajo, y esto se debe a que solo el 8% de contribuyentes pagaron y por tanto dejándose de recaudar más del 90% de ingresos.Tesi

Factores de riesgo asociados a término de embarazo por cesárea versus vía vaginal en partos prematuros del Hospital Nacional Edgardo Rebagliati Martins julio - diciembre 2023

El parto pretérmino se define como el término de la gestación que ocurre entre las 22 a 36 semanas y 6 días. La incidencia de los partos pretérmino está en ascenso tanto a nivel nacional como mundial a pesar de los avan ces científicos y tecnológicos. Objetivo: Determinar los principales factores de riesgo para término de gestación pretérmino por cesárea comparado con la vía vaginal en partos prematuros del Hospital Nacional Edgardo Rebagliati Martins durante Julio-diciembre 2023. Material y métodos: Se llevó a cabo un estudio de caso-control. La muestra estuvo conformada por gestantes pretérmino que culminaron su embarazo en el Hospital Nacional Edgardo Rebagliati Martins. En este estudio se determinaron los factores de riesgo asociados al término de gestación prematura por cesárea (casos) en relación a partos prematuros nacidos por vía vaginal (control). Se recopilaron datos de las historias clínicas electrónicas y el registro manual de partos y cesáreas del hospital Nacional Edgardo Rebagliati Martins. El análisis se hizo en el software SPSS, versión 23.0. Se aplicaron técnicas estadísticas para la asociación entre las variables dependientes y las variables independientes. Los factores asociados a una cesárea fueron analizados a través de los odds ratio (OR) crudos y ajustados. Para evaluar la diferencia estadística entre variables cuantitativas se usó la prueba “T de student”, y para la asociación entre la vía final del parto y las variables cualitativas se usó la prueba de Chi cuadrado y de Pearson. Se utilizó un nivel de significancia de 0,05. Resultados: La preeclamsia tiene un Odds Ratio de 4.5 como factor de riesgo para terminar en cesárea en prematuros. Conclusión: En el hospital Rebagliati la preeclamsia es uno de los factores de riesgo más importante y preponderante para el término de gestación por cesárea en partos prematuros