Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of the type VII collagen gene. In this study, we assessed the expression of type VII collagen and TGF-beta in the skin of patients with SSc. Indirect immunofluorescence showed an abundance of type VII collagen in the patients\u27 skin, including the dermis. Ultrastructural analysis of SSc skin revealed an abundance of fibrillar material, possibly representing type VII collagen. The increased expression of type VII collagen epitopes was accompanied by the elevated expression of immunodetectable TGF-beta 1 and TGF-beta 2. Dermal fibroblasts cultured from the affected individuals showed a statistically significant (P \u3c 0.02) increase in the expression of type VII collagen at the mRNA level, as detected by reverse transcription-PCR with a mutated cDNA as an internal standard, and increased deposition of the protein as assessed by indirect immunofluorescence. Thus, type VII collagen is abundantly present in SSc patients\u27 dermis, a location not characteristic of its normal distribution, and its aberrant expression may relate to the presence of TGF-beta in the same topographic distribution. The presence of type VII collagen in the dermis may contribute to the tightly bound and indurated appearance of the affected skin in SSc patients

The balance between fumarate and malate plays an important role in plant development and postharvest quality in tomato fruit

Organic acids, produced as intermediates of the tricarboxylic cycle, play a crucial role in the plant primary metabolism and are considered as being ones of the most important quality traits in edible fruits. Even if they are key metabolites in a multitude of cellular functions, little is known about their physiological relevance and regulation. Transgenic tomato (Solanum lycopersicum) plants expressing constitutively a bacterial maleate isomerase, which converts reversibly maleate to fumarate, were generated in order to improve our knowledge about the role of organic acids in the crop and fruit metabolism. Growth and reproduction were affected by the unbalance of tricarboxylic cycle intermediates, as a dwarf phenotype and a flowering delay were observed in the transgenic plants. In addition, a delay in chlorophyll synthesis, a decrease in the numbers of stomata and significant changes in some photosynthetic parameters indicated alterations in central primary metabolism. Postharvest was also impaired, as transgenic fruits showed increased water lost and deterioration, indicating a possible role of the organic acids in cell wall metabolism. Finally, preliminary metabolomics analysis pointed out important changes during fruit ripening in flavor-related metabolites, such as acids and sugars, revealing the importance of organic acids in fruit metabolism. Taken together, these data indicate a pivotal role of tricarboxylic cycle intermediates, such as malate or fumarate, as regulatory metabolites. Besides their role in quality fruit characteristics, they are involved in a multitude of functions including growth and photosynthesis.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ácidos biliares y transaminasas séricas como predictores de complicaciones fetales en gestantes con colestasis intrahepática. Hospital Nacional Alberto Sabogal Sologuren. Callao. 2015 - 2016

Objetivo: Determinar si los ácidos biliares y transaminasas séricas son predictores de complicaciones fetales en gestantes con Colestasis Intrahepática en el Hospital Nacional Alberto Sabogal Sologuren. Material y métodos: Estudio de pruebas diagnósticas, retrospectivo, observacional, en 73 gestantes con colestasis intrahepatica estableciéndose dos grupos de estudio de 43 y 30 gestantes de acuerdo a la presencia o ausencia de complicaciones fetales. Se calculó la sensibilidad, especificidad, valor predictivo positivo y negativo. Se aplicó el test de chi cuadrado y área bajo la curva. Resultados: Los puntos de corte encontrados fueron los siguientes; ácidos biliares séricos: 35.5 umol/L, Alanina aminotransferasa: 56.5 U/L y para Aspartato aminotransferasa 76.5 U/L. La sensibilidad, especificidad, VPP y VPN de los ácidos biliares fueron 76,74%; 90.0%; 91.67%; 91.67% y 72.97% respectivamente. Con respecto a las transaminasas; para la Alanina aminotransferasa se encontró: sensibilidad 55.81%, especificidad: 63.33; VPP: 68.57%; VPN: 50 y en el caso del Aspartato aminotransferasa se obtuvo: sensibilidad: 62.79%, especificidad: 70%, VPP: 75% y VPN: 56.8% y el área bajo la curva para los ácidos biliares de 0.887 Conclusiones: Los ácidos biliares y transaminasas séricas son predictores de complicaciones fetales en gestantes con Colestasis Intrahepática.Objective: To determine if bile acids and serum transaminases are predictors of fetal complications in pregnant women with Intrahepatic Cholestasis at the Alberto Sabogal Sologuren National Hospital. Material and methods: A retrospective, observational study of diagnostic tests in 73 pregnant women with intrahepatic cholestasis, establishing two study groups of 43 and 30 pregnant women according to the presence or absence of fetal complications. Sensitivity, specificity, positive and negative predictive value were calculated. The chi square test and area under the curve were applied. Results: The cut-off points found were as follows; Serum bile acids: 35.5 umol / L, Alanine aminotransferase: 56.5 U / L and for Aspartate aminotransferase 76.5 U / L. The sensitivity, specificity, VPP and NPV of bile acids were 76.74%; 90.0%; 91.67%; 91.67% and 72.97% respectively. With regard to transaminases; For the Alanine aminotransferase was found: sensitivity 55.81%, specificity: 63.33; VPP: 68.57%; VPN: 50 and in the case of Aspartate aminotransferase: sensitivity: 62.79%, specificity: 70%, PPV: 75% and NPV: 56.8% and the area under the curve for bile acids of 0.887 Conclusions: Bile acids and serum transaminases are predictors of fetal complications in pregnant women with Intrahepatic Cholestasis.Tesi

Tumor suppressor ARF regulates tissue microenvironment and tumor growth through modulation of macrophage polarization

Tumor microenvironment has been described to play a key role in tumor growth, progression, and metastasis. Macrophages are a major cellular constituent of the tumor stroma, and particularly tumor associated macrophages (TAMs or M2-like macrophages) exert important immunosuppressive activity and a pro-tumoral role within the tumor microenvironment. Alternative-reading frame (ARF) gene is widely inactivated in human cancer. We have previously demonstrated that ARF deficiency severely impairs inflammatory response establishing a new role for ARF in the regulation of innate immunity. On the basis of these observations, we hypothesized that ARF may also regulates tumor growth through recruitment and modulation of the macrophage phenotype in the tumor microenvironment. Xenograft assays of B16F10 melanoma cells into ARF-deficient mice resulted in increased tumor growth compared to those implanted in WT control mice. Tumors from ARF-deficient mice exhibited significantly increased number of TAMs as well as microvascular density. Transwell assays showed crosstalk between tumor cells and macrophages. On the one hand, ARF-deficient macrophages modulate migratory ability of the tumor cells. And on the other, tumor cells promote the skewing of ARF-/- macrophages toward a M2-type polarization. In conclusion, these results demonstrate that ARF deficiency facilitates the infiltration of macrophages into the tumor mass and favors their polarization towards a M2 phenotype, thus promoting tumor angiogenesis and tumor growth. This work provides novel information about the critical role of ARF in the modulation of tumor microenvironment.This study was supported by grant PI11.0036 and PI14.0055 from the FIS, MPY 1410/09 from ISCIII and Spanish Ministry of Health (Instituto de Salud Carlos III; RD12/0036/0059) to SH, and by grant TPY-M-1068/13 and IERPY 1149/16 to AL. L J-G was supported by FIS (FI12/00340). AL was supported by FIS (CP12/03087). S Herranz was supported by TPY-M-1068/13 from ISCIII. We thank Fernando González Camacho and Silvia Hernández Esteban for Confocal Microscopy assistance.S

Prospeccion de la comercializacion de plantas medicinales en la VII Region del Maule

Resumen (Spanish, English)87 p.En Chile, se encuentran más de 500 especies do plantas autóctonas y silvestres las cuales se han utilizado tradicionalmente en la medicina popular. Existe un mercado formal e informal que hoy en día sigue comercializando algunas de estas hierbas, las cuales generalmente se obtienen de la recolección silvestre, lo que ha disminuido su población natural. Con el objetivo de estimar el volumen de extracción, precio, lugares de recolección, y analizar los distintos canales de comercialización para 15 especies de plantas medicinales, se registraron los comerciantes de hierbas tanto en el mercado formal como informal, en nueve comunas de fa Región del Maule. Se aplicó un cuestionario estructurado a los comerciantes de este tipo de productos. Tres de las comunas encuestadas carecen de un mercado formal. Todos los comerciantes encuestados conocen y comercializan las especies bailahuén, boldo, pichipiedra, sanguinaria, y zarzaparrilla, mientras que el Quelén-Quelén solo se conoce en las comunas de Curico, Molina y Talca. Solo el 20% de los encuestados recolecta sus productos personalmente, siendo la mayoría de ellos mayores de edad

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response

The endothelial layer is essential for maintaining homeostasis in the body by controlling many different functions. Regulation of the inflammatory response by the endothelial layer is crucial to efficiently fight against harmful inputs and aid in the recovery of damaged areas. When the endothelial cells are exposed to an inflammatory environment, such as the outer component of gram-negative bacteria membrane, lipopolysaccharide (LPS), they express soluble pro-inflammatory cytokines, such as Ccl5, Cxcl1 and Cxcl10, and trigger the activation of circulating leukocytes. In addition, the expression of adhesion molecules E-selectin, VCAM-1 and ICAM-1 on the endothelial surface enables the interaction and adhesion of the activated leukocytes to the endothelial layer, and eventually the extravasation towards the inflamed tissue. In this scenario, the endothelial function must be tightly regulated because excessive or defective activation in the leukocyte recruitment could lead to inflammatory-related disorders. Since many of these disorders do not have an effective treatment, novel strategies with a focus on the vascular layer must be investigated. We propose comprehensive assays that are useful to the search of novel endothelial regulators that modify leukocyte function. We analyze endothelial activation by using specific expression targets involved in leukocyte recruitment (such as, cytokines, chemokines, and adhesion molecules) with several techniques, including: real-time quantitative polymerase chain reaction (RT-qPCR), western-blot, flow cytometry and adhesion assays. These approaches determine endothelial function in the inflammatory context and are very useful to perform screening assays to characterize novel endothelial inflammatory regulators that are potentially valuable for designing new therapeutic strategies.This work was supported by the Ministerio de Economía y Competitividad (MINECO) and the Instituto de Salud Carlos III (ISCIII) (grant number IERPY 1149/16 to A.L.; MPY 1410/09 to S. Hortelano); by the MINECO through the Fondo de Investigación en Salud (FIS) (grants numbers PI11.0036 and PI14.0055 to S. Hortelano). S. Herranz was supported by IERPY 1149/16 from ISCIII.S

Relación entre el clima organizacional y el desempeño docente en las II.EE. de la RED No. 09, UGEL No. 05 distrito de SJL. Lima; 2012

El presente trabajo de investigación tuvo como objetivo determinar como el Clima Organizacional se relaciona con el Desempeño Docente en las II.EE. de la Red N° 09, UGEL N° 05 Distrito de SJL. Lima; 2012. El tipo de estudio empleado en esta investigación se tipificó como descriptivo y correlacional. En cuanto al diseño de investigación empleado en esta investigación es de tipo no experimental, es de carácter transversal.En cuanto a la población de estudio está constituida por 580 docentes Red Educativa 09 de San Juan de Lurigancho – UGEL 05. Para seleccionar la muestra se utilizó la técnica de muestreo aleatorio estratificado, eligiendo 185 docentes. En la investigación se concluye que el clima organizacional se relaciona directamente con el desempeño docente en las II. EE.de la Red Nº 09,UGEL Nº 05 distrito de SJL.Lima;2012

Gastos deducibles y no deducibles y el impuesto a la renta de tercera categoría en las empresas industriales, Callao, 2021

El presente desarrollo de tesis tiene como objetivo general analizar de qué manera los gastos deducibles y no deducibles se relacionan con el impuesto a la renta de tercera categoría de las empresas industriales, Callao, 2021; el cual se elaboró a través de la metodología de tipo cuantitativo, correlacional, básica y diseño no experimental. Como técnica de recolección de datos se empleó la encuesta y como instrumento de recolección el cuestionario, el cual consta de 20 ítems (12 y 8 ítems correspondientes a cada una de las variables), aplicado a una muestra de 51 colaboradores del área contable del sector pesquero del distrito del Callao; para lo cual dicho cuestionario será sometido y validado con la base de datos Excel y el programa estadístico SPSS para identificar la correlación entre la variable 1 y variable 2 y a su vez determinar la confiabilidad del instrumento aplicado. Se concluye que los gastos deducibles y no deducibles se relacionan con el impuesto a la renta de tercera categoría en las empresas industriales del Callao, 2021, destacando que la mala aplicación de los gastos sujetos a límite y la deducción de gastos no deducibles generará que se realicen reparos tributarios

Accesibilidad universal: Barreras físicas arquitectónicas como limitantes del hábitat social para personas con discapacidad en el distrito de Ventanilla, Lima, 2022

En una ciudad con un crecimiento urbano desordenado, se originan espacios marginados y segregados, donde la presencia del estado es paupérrima, por ello, este estudio tiene la finalidad de identificar y analizar la relación existente de las barreras físicas arquitectónicas como limitantes del hábitat social para las personas con discapacidad, en relación con el pensamiento Moriniano y el objetivo 11.3 de las ODS. La metodología fue de tipo sustantiva, enfoque cualitativo de tipo fenomenológico, nivel descriptivo, diseño no experimental y corte longitudinal. Se contó con una muestra de 66 personas con discapacidad, aplicando técnicas para la recolección de datos a la población y especialistas multidisciplinarios, nacionales e internacionales. Se validó el instrumento mediante la confiabilidad del Alfa de Cronbach, a través de la prueba piloto del test y re-test respondida por 17 personas. Las fichas de observación y las entrevistas estructuradas, se codificaron por el software cualitativo ATLAS.ti9, en cambio, la encuesta fue por el software cuantitativo MAXQDA, concluyendo que las personas con discapacidad y sus familiares del asentamiento humano Cerro Cachito, no consideran este espacio físico como un parque, debido a las barreras existentes que niega su participación social, en consecuencia, buscan espacios públicos en otros distritos para poder ejercer su participación social

The mutational landscape of human olfactory G protein-coupled receptors

Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain. OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset. We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population. https://doi.org/10.13039/5011000110335https://doi.org/10.13039/5011000110333https://doi.org/10.13039/5011000110336https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033_https://doi.org/10.13039/501100011033_https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ahttps://doi.org/10.13039/501100011033ghttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033chttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ehttps://doi.org/10.13039/501100011033shttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033lhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033dhttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033vhttps://doi.org/10.13039/501100011033ehttps://doi.org/10.13039/501100011033shttps://doi.org/10.13039/501100011033thttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033ghttps://doi.org/10.13039/501100011033ahttps://doi.org/10.13039/501100011033chttps://doi.org/10.13039/501100011033ihttps://doi.org/10.13039/501100011033óhttps://doi.org/10.13039/501100011033nhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033dhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033$https://doi.org/10.13039/501100011033fhttps://doi.org/10.13039/501100011033 https://doi.org/10.13039/501100011033Phttps://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/501100011033Dhttps://doi.org/10.13039/5011000110332https://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110331https://doi.org/10.13039/5011000110339https://doi.org/10.13039/501100011033-https://doi.org/10.13039/5011000110331https://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110339https://doi.org/10.13039/5011000110332https://doi.org/10.13039/5011000110334https://doi.org/10.13039/5011000110330https://doi.org/10.13039/501100011033Rhttps://doi.org/10.13039/501100011033Bhttps://doi.org/10.13039/501100011033-https://doi.org/10.13039/501100011033Ihttps://doi.org/10.13039/5011000110330https://doi.org/10.13039/5011000110330https://doi.org/10.13039/50110001103