Mutations in TGM6 induce the unfolded protein response in SCA35

Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations in TG6 induce cerebellar degeneration by an unknown mechanism. We identified seven patients bearing new mutations in TGM6. To gain insights into the molecular basis of mutant TG6-induced neurotoxicity, we analyzed all of the seven new TG6 mutants and the five TG6 mutants previously linked to SCA35. We found that wild-type (TG6-WT) mainly localized to the nucleus and perinuclear area, whereas five TG6 mutations showed nuclear depletion, increased accumulation in the perinuclear area, insolubility and loss of enzymatic function. Aberrant accumulation of these TG6 mutants in the perinuclear area led to activation of the unfolded protein response (UPR), suggesting that specific TG6 mutants elicit an endoplasmic reticulum (ER) stress response. Mutations associated with activation of the UPR caused death of primary neurons and reduced the survival of novel D. melanogaster models of SCA35. These results indicate that mutations differently impacting on TG6 function cause neuronal dysfunction and death through diverse mechanisms and highlight the UPR as a potential therapeutic target for patient treatment

The role of an electronic alert system to detect acute kidney injury in hospitalized patients: DETECT-H Project

Background and aims: Acute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis. Methods: A fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines. Results: In six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80–5.59) and a LOS 1.52 (1.11–2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified. Conclusions: CKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes. Resumen: Introducción y objetivos: El fracaso renal agudo (FRA) aumenta la mortalidad y la estancia hospitalarias (EH). El empleo de sistemas de detección electrónica podría ser una herramienta beneficiosa para mejorar estos resultados. Métodos: Se desarrolló un sistema de detección automático a tiempo real de pacientes ingresados con función renal alterada, denominado proyecto DETECT-H. El FRA se estableció de acuerdo con las guías KDIGO. Resultados: En 6 meses, 1.241 alertas fueron recogidas de 11.022 ingresos. La incidencia global del FRA fue del 7,7%. La distribución en función del estadio máximo del FRA alcanzado fue: estadio 1: 49,8%, estadio 2: 24,5% y estadio 3: 25,8%; con una mortalidad hospitalaria del 10,9, 22,7 y 33,9%, respectivamente. En el caso del FRA con necesidad de diálisis fue del 57,1%. La mortalidad en pacientes con enfermedad renal crónica (ERC) estable fue del 4,3%. La mediana de EH en pacientes detectados fue 8 vs. 5 días para todos los pacientes hospitalizados. El FRA se asoció con una mortalidad 3,18 (1,8-5,59) y una EH 1,52 (1,11-2,08) veces superior que aquellos ingresos sin FRA. El análisis multivariante indicó que el FRA se asociaba con la EH > 8 días.En los informes de alta, la presencia de ERC previa solo fue registrada en el 31,9% de los pacientes con ERC y el FRA hospitalario en el 45,3%. Conclusiones: La ERC y el FRA intrahospitalario son entidades infradiagnosticadas. La mortalidad y la EH están aumentadas en pacientes con disfunción renal. La gravedad del FRA se asoció con mayor mortalidad y EH. Un sistema de detección automático para identificarlos podría ser útil para mejorar estos resultados. Keywords: Acute kidney injury, Automated electronic detection system, Chronic kidney disease, Diagnosis, Health information technology, Mortality, Palabras clave: Fracaso renal agudo, Sistema de detección electrónica automática, Enfermedad renal crónica, Diagnóstico, Tecnología de información de la salud, Mortalida

The ACER pollen and charcoal database: a global resource to document vegetation and fire response to abrupt climate changes during the last glacial period

Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard–Oeschger (D–O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D–O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73–15 ka) with a temporal resolution better than 1000 years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (14C, 234U∕230Th, optically stimulated luminescence (OSL), 40Ar∕39Ar-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft AccessTM at https://doi.org/10.1594/PANGAEA.870867

A serological assay to detect SARS-CoV-2 seroconversion in humans

Development of an enzyme-linked immunosorbent assay to detect antibodies to the SARS-CoV-2 spike protein in human sera and plasma. Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.Peer reviewe

Violencia Escolar En El Centro Educativo Ceat General Sede Jhon F. Kennedy Del Municipio De Yumbo Departamento Del Valle Del Cauca

La sociedad colombiana esta viviendo un deterioro progresivo debido a la descomposición social generada por las malas relaciones de convivencia en el seno de la familia y de las diferentes comunidades que hacen parte del territorio nacional lo que esta llevando a un Estado de neurosis colectiva donde cada individuo reacciona de manera agresiva o violenta ante sus semejantes perdiéndose el respeto por la vida, los valores de los demás; haciendo que las personas actúen para hacer justicia por sus propios medios.PregradoLicenciado en Pedagogía Infantí

Fresh Mint: Frescura a tu alcance!!!

Seminario Desarrollo de Emprendedores. 2013. Carrera Odontología . Docente Lic. Vivas, Rosa María.Propuesta de empresa manufacturera de enjuague bucal a base de polvo que ayuda al control de bacterias y prevenir el mal aliento. Se trata de un producto de bajo costo que utiliza como materia prima carbonato de sodio, triclosan y menta. El producto, acompañado de un correcto cepillado, mantiene la boca libre de bacterias. Su mercado potencial son los habitantes del Distrito III, IV y V que tienen un ingreso superior a los 10,000 córdobas mensuales

Ethylene sensitivity and relative air humidity regulate root hydraulic properties in tomato plants

The effect of ethylene and its precursor ACC on root hydraulic properties, including aquaporin expression and abundance, is modulated by relative air humidity and plant sensitivity to ethylene. Relative air humidity (RH) is a main factor contributing to water balance in plants. Ethylene (ET) is known to be involved in the regulation of root water uptake and stomatal opening although its role on plant water balance under different RH is not very well understood. We studied, at the physiological, hormonal and molecular levels (aquaporins expression, abundance and phosphorylation state), the plant responses to exogenous 1-aminocyclopropane-1-carboxylic acid (ACC; precursor of ET) and 2-aminoisobutyric acid (AIB; inhibitor of ET biosynthesis), after 24 h of application to the roots of tomato wild type (WT) plants and its ET-insensitive never ripe (nr) mutant, at two RH levels: regular (50%) and close to saturation RH. Highest RH induced an increase of root hydraulic conductivity (Lp(o)) of non-treated WT plants, and the opposite effect in nr mutants. The treatment with ACC reduced Lp(o) in WT plants at low RH and in nr plants at high RH. The application of AIB increased Lp(o) only in nr plants at high RH. In untreated plants, the RH treatment changed the abundance and phosphorylation of aquaporins that affected differently both genotypes according to their ET sensitivity. We show that RH is critical in regulating root hydraulic properties, and that Lp(o) is affected by the plant sensitivity to ET, and possibly to ACC, by regulating aquaporins expression and their phosphorylation status. These results incorporate the relationship between RH and ET in the response of Lp(o) to environmental changes

Insights into the economic situation of seabream and seabass companies in the Mediterranean area

This contribution aims to provide an economic assessment of the seabream and seabass industry in the Mediterranean, in order to describe the recent development and current situation of the economy and markets of this industry. It focuses on analyzing the economic and financial structure at different levels of aggregation (industry, company, and farms). The study is carried out through a descriptive analysis of information obtained from primary and secondary sources. The work starts with an analysis at the industry level that considers the productive structure, incomes and costs, and economic performance indicators. This analysis is carried out for the industry as a whole, but it is also disaggregated by production segments and countries. Moreover, it provides information about international trade and consumption. The data used come from secondary sources, mainly STECF, FAO and Eurostat. Secondly, the work addresses the study of the economic and financial situation of farming companies in the Mediterranean area with data from primary and secondary sources. Again, the analysis is performed for the industry as a whole and disaggregated by countries, but also by company size. The analyses also provides a property map of the companies identified as seabream and seabass farms. Finally, we use primary data obtained in the context of the MedAID project (Grant Agreement Nº 727315) in which this work has been performed, to develop an economic analysis at facility level