Putting the pieces together : elucidation of podocyte biology in the homeostasis of the kidney filtration barrier

End-stage renal disease (ESRD) is a devastating condition that can only be treated with chronic dialysis or kidney transplantation. ESRD treatment costs account for up to 10% of healthcare budgets in the Western world. The 5-year survival for patients in dialysis is only about 40%. Glomerular disease processes are the main cause of ESRD. Despite this, our basic knowledge on the biology and disease processes of the glomerulus is poor. As a result, we still lack effective therapy options to stop the progression of glomerular diseases. In this thesis we have identified a number of candidate genes and proteins that could have an essential role in the glomerular homeostasis. In the first project, we identified a group of neural proteins, Hip1, Nfasc and Olfml2, which are enriched in podocytes. We used these markers to provide further evidence that podocytes are present in glomerular crescent lesions that occur in inflammatory diseases of the glomerulus. In project 2, we studied the functional role of another neural protein, dendrin, in the kidney by generating and characterizing a knockout (KO) mouse line. Previously, we and others have shown that dendrin is very specific to podocytes and interacts with cd2ap and nephrin, two podocyte proteins imperative for the maintenance of the kidney barrier. The KO mouse model showed that dendrin is not needed for the development or maintenance of the glomerulus filtration barrier. Furthermore, the outcome of glomerular disease in two injury models was unaffected by the absence of dendrin. This suggests that dendrin does not have a role in the development of glomerular damage in these two models. In project 3, we identified Tmem234, Slfn5, Lrrc49 and Znf185 as highly podocyte-enriched molecules. Morpholino knockdown experiments in zebrafish showed that the silencing of Tmem234 results in podocyte foot effacement and proteinuria in pronephros. Thus, Tmem234 seems to have an important role in the formation of functional filtration barrier in zebrafish pronephros, and therefore it is reasonable to speculate that it can have also an important role in the mammalian kidney. Lastly, in project 4 we identified a mediator protein subunit, Med22, to be essential for the kidney filtration barrier. In zebrafish pronephros, Med22 morphants exhibit defective capillary loop formation and leak large proteins to tubuli. In mice, full KO mice die during embryonic development. In podocyte-specific KO animals kidney development proceeds normally. However, these mice exhibit proteinuria starting from 8 weeks of age that progresses to ESRD by 16 weeks of age. Histological analysis shows the accumulation of caveolin-positive vesicles in the cytoplasm of podocytes. As these vesicles became larger, we detected the loss of podocytes that leads to glomerulosclerosis and ESRD. Thus, Med22 seems to regulate vesicular trafficking in podocytes and be essential for podocyte survival. This thesis provides novel insights into podocyte biology and obviously opens up new possibilities to study these candidate genes in glomerular function and pathology

Las competencias directivas y su relación con el desempeño en las pequeñas y medianas empresas familiares

The objective of the research is to analyze the relationship between managers’ competencies and their businesses performance. The study was approached from the quantitative paradigm, applying a questionnaire to 114 managers of small and medium-sized family businesses, located in the states of Tamaulipas and San Luis Potosí, Mexico. The results shared show, in the context of a family business, the relationship between the study variables, which allows providing knowledge in the family businesses management, which are important economic units in this country, as sources of employment generation. The structural equations technique was applied in the validation of the research hypotheses. It is inferred that only intrategic and personal effectiveness competencies are positively related to organizational performance, with no positive relationship between strategic competencies and organizational performance.La presente investigación tiene como objetivo analizar la relación existente entre las competencias de los directivos con el desempeño de sus negocios. Para ello se abordó el estudio desde el enfoque cuantitativo, aplicando un cuestionario estructurado a 114 empresarios de pequeñas y medianas empresas familiares de los estados de Tamaulipas y San Luis Potosí, México; este trabajo comparte los resultados del piloto del cuestionario para explorar su construcción al contexto empresarial de las empresas familiares. Se aplicó la técnica de ecuaciones estructurales para la validez de constructos y de las hipótesis de investigación. Se infiere que no todas las competencias de los gerentes están relacionadas con los resultados empresariales

A Fungal Effector With Host Nuclear Localization and DNA-Binding Properties Is Required for Maize Anthracnose Development

Plant pathogens have the capacity to manipulate the host immune system through the secretion of effectors. We identified 27 putative effector proteins encoded in the genome of the maize anthracnose pathogen Colletotrichum graminicola that are likely to target the host’s nucleus, as they simultaneously contain sequence signatures for secretion and nuclear localization. We functionally characterized one protein, identified as CgEP1. This protein is synthesized during the early stages of disease development and is necessary for anthracnose development in maize leaves, stems, and roots. Genetic, molecular, and biochemical studies confirmed that this effector targets the host’s nucleus and defines a novel class of double-stranded DNA-binding protein. We show that CgEP1 arose from a gene duplication in an ancestor of a lineage of monocot-infecting Colletotrichum spp. and has undergone an intense evolution process, with evidence for episodes of positive selection. We detected CgEP1 homologs in several species of a grass-infecting lineage of Colletotrichum spp., suggesting that its function may be conserved across a large number of anthracnose pathogens. Our results demonstrate that effectors targeted to the host nucleus may be key elements for disease development and aid in the understanding of the genetic basis of anthracnose development in maize plants.Fil: Vargas, Walter Alberto. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanz Martín, José M.. Universidad de Salamanca; EspañaFil: Rech, Gabriel E.. Universidad de Salamanca; EspañaFil: Armijos Jaramillo, Vinicio D.. Universidad de Salamanca; EspañaFil: Rivera Rodriguez, Lina Patricia. Universidad de Salamanca; EspañaFil: Echeverria, María de Las Mercedes. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Díaz Mínguez, José M.. Universidad de Salamanca; EspañaFil: Thon, Michael R.. Universidad de Salamanca; EspañaFil: Sukno, Serenella A.. Universidad de Salamanca; Españ

La Agresividad

La presente tésis, debe interpretarse como una herramienta de orden investigativo a nivel institucional, como parte de una preparación profesional en los campos de la enseñanza, la consejería, la terápia de grupo o la psicología; presentando un material de gran interés para la aplicación de la investigación sobre la conducta agresiva infantíl. El texto muestra como aplicar la información y las ideas derivadas de la investigación en la psicología educativa, y la pedagogía para resolver la factores que inciden en el comportamiento agresivo que se presenta en el ámbito escolar. A fin de explorar las conexiones entre el conocimiento y la práctica que sirva de apoyo a la comunidad educativa que permite al fin elevar una mejor vida social.Introducción 11. La Agresividad 22. Planteamiento Del Problema 3PregradoLicenciado en Pedagogía Infantí

Stated benefits from urban afforestation in an arid city: a contingent valuation in Mexicali, Baja California, Mexico

The pervasiveness of particulate matter in arid cities has yet to be discussed and tackled. Given that urban trees have been documented to provide air-filtering and dry deposition services, this study documents the stated benefits from an urban afforestation scenario in Mexicali –an arid city located northwest Mexico at the US-Mexico border. Our doublebounded dichotomous contingent valuation protocol yields an estimated average annual willingness to pay (WTP) of USD 88 per household. Variations in the WTP are associated with perception of air quality and presence of respiratory symptoms in the respondent’s household. The smallest WTP (USD 75) is reported by respondents perceiving poor air quality in their neighborhood and with no household members affected by respiratory symptoms. In contrast, respondents perceiving good air quality and with at least one household member facing respiratory symptoms reported a WTP of USD 99. The average stated benefits represent around 0.8% of the annual household income

Stated benefits from air quality improvement through urban afforestation in an arid city – A contingent valuation in Mexicali, Baja California, Mexico

Cities in drylands are expected to experience increasing challenges when it comes to air pollution. Currently, concentrations of particulate matter in these cities frequently reach dangerous levels. Urban afforestation represents an alternative to increase human health in arid cities via air-filtering and dry deposition. By simulating a non-existing market through a contingent valuation protocol, this study estimates the willingness to contribute monetarily to an urban afforestation scenario in Mexicali -an arid city located at the US-Mexico border. We estimate an average annual willingness to pay (WTP) of (2019) USD 88 per household. Variations in WTP are associated with the respondent's perception of air quality and the presence of respiratory symptoms in the respondent's household. The smallest WTP (USD 75) is reported by those perceiving poor air quality in their neighborhood and with no household members affected by respiratory symptoms. Respondents perceiving good air quality and with at least one household member facing respiratory symptoms report a WTP of USD 99. The highest WTP represents around 0.8 % of the annual household income. This WTP, when extrapolated to and aggregated over the total number of households in Mexicali, justifies the implementation of an urban afforestation program supplying 30 thousand tree seedlings annually

Sensitive Periods for Psychosocial Risk in Childhood and Adolescence and Cardiometabolic Outcomes in Young Adulthood

Greater psychosocial risk in childhood and adolescence predicts poorer cardiometabolic outcomes in adulthood. We assessed whether the timing of psychosocial risk from infancy through adolescence predicts cardiometabolic outcomes in young adulthood. Young adults and their mothers participated in a longitudinal study beginning in infancy in Santiago, Chile (N = 1040). At infancy, 5 years, 10 years, and adolescence, mothers reported on depressive symptoms, stressful experiences, support for child development in the home, father absence, parental education, and socioeconomic status (SES) to create a psychosocial risk composite at each time point. Young adults (52.1% female; 21–27 years) provided fasting serum samples and participated in anthropometric and blood pressure (BP) assessments, including a dualenergy X-ray absorptiometry (DXA) scan for measuring body fat. Greater infant psychosocial risk was associated with a greater young adult metabolic syndrome score (β = 0.07, 95% confidence intervals (CI): 0.01 to 0.13, p = 0.02), a higher body mass index and waist circumference composite (β = 0.08, 95% CI: 0.03 to 0.13, p = 0.002), and a higher body fat (DXA) composite (β = 0.07, 95% CI: 0.01 to 0.12, p = 0.02). No psychosocial risk measure from any time point was associated with BP. Infant psychosocial risk predicted cardiometabolic outcomes in young adulthood better than psychosocial risk at 5 years, 10 years, or adolescence, mean of psychosocial risk from infancy through adolescence, and maximum of psychosocial risk at any one time. Consistent with the Developmental Origins of Health and Disease model, findings suggest that infancy is a sensitive period for psychosocial risk leading to poorer cardiometabolic outcomes in young adulthood

NFkB in the development of endothelial activation and damage in uremia: an in vitro approach

Impaired hemostasis coexists with accelerated atherosclerosis in patients with chronic kidney disease (CKD). The elevated frequency of atherothrombotic events has been associated with endothelial dysfunction. The relative contribution of the uremic state and the impact of the renal replacement therapies have been often disregarded. Plasma markers of endothelial activation and damage were evaluated in three groups of patients with CKD: under conservative treatment (predialysis), on hemodialysis, and on peritoneal dialysis. Activation of p38 MAPK and the transcription factor NFκB was assessed in endothelial cell (EC) cultures exposed to pooled sera from each group of patients. Most of the markers evaluated (VCAM-1, ICAM-1, VWF, circulating endothelial cells) were significantly higher in CDK patients than in controls, being significantly more increased in the group of peritoneal dialysis patients. These results correlated with the activation of both p38 MAPK and NFκB in EC cells exposed to the same sera samples, and also to the peritoneal dialysis fluids. Hemodialysis did not further contribute to the endothelial damage induced by the uremic state observed in predialysis patients, probably due to the improved biocompatibility of the hemodialysis technique in recent years, resulting in lower cellular activation. However, peritoneal dialysis seemed to exert a significant proinflammatory effect on the endothelium that could be related to the high glucose concentrations and glucose degradation products present in the dialysis fluid. Although peritoneal dialysis has been traditionally considered a more physiological technique, our results raise some doubts with respect to inflammation and EC damage

Leaf Blast \u3cem\u3e Pyricularia grisea \u3c/em\u3e Effects on Buffelgrass Forage and Seed Production in Northwestern Mexico

Common buffelgrass Cenchrus ciliaris (T-4464) is an introduced species intensively planted in Mexico to increase productivity on rangelands. Studies have shown that the species produces 5 to 10 times more forage as compared to native species on rangelands (Martin et al., 1995). Previous studies in the Gulf of Mexico have shown that the fungus Pyricularia grisea causes a disease in buffelgrass known as leaf blight and induce serious damage to the plant affecting forage production and nutritive quality (Ocumpaugh and Rodríguez, 1998; González, 2002). Injuries begin in the inferior leafs as small dark stains that later are converted in injuries bronze color of round and elliptic form, necrotic, with dark red margins and with a chlorotic yellow halo (Rodriguez et al., 1999). A high humidity and temperature condition in the Pacific Northwest during the last years is believed to be creating ideal conditions for Pyricularia which is suspected to affect buffelgrass. Currently, no data are available in this region to confirm fungus presence and its impact on forage and seed productivity on buffelgrass pastures. The study was conducted at north central Sonora, Mexico to: a) evaluate the incidence and damage intensity of Pyricularia grisea in buffelgrass pastures and b) to determine its impact on forage and seed production

Beliefs among Physicians in the Diagnostic and Therapeutic Approach to Non-small Cell Lung Cancer

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