The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport

Ubiquitination regulates several biological processes, however the role of specific members of the ubiquitinome on intracellular membrane trafficking is not yet fully understood. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1187 genes of the human “ubiquitinome” using amyloid precursor protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 with Capzimin (CZM) caused a robust increase in APP levels at the Golgi apparatus and the swelling of this organelle. We showed that this phenotype is the result of rapid inhibition of Golgi-to-ER retrograde transport, a pathway implicated in the early steps of the autophagosomal formation. Indeed, we observed that inhibition of PSMD14 with CZM acts as a potent blocker of macroautophagy by a mechanism related to the retention of Atg9A and Rab1A at the Golgi apparatus. As pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and the K63-Ub chains, act as a crucial regulatory factor for macroautophagy by controlling Golgi-to-ER retrograde transport

Negative Modulation of Macroautophagy by Stabilized HERPUD1 is Counteracted by an Increased ER-Lysosomal Network With Impact in Drug-Induced Stress Cell Survival

Macroautophagy and the ubiquitin proteasome system work as an interconnected network in the maintenance of cellular homeostasis. Indeed, efficient activation of macroautophagy upon nutritional deprivation is sustained by degradation of preexisting proteins by the proteasome. However, the specific substrates that are degraded by the proteasome in order to activate macroautophagy are currently unknown. By quantitative proteomic analysis we identified several proteins downregulated in response to starvation independently of ATG5 expression. Among them, the most significant was HERPUD1, an ER membrane protein with low expression and known to be degraded by the proteasome under normal conditions. Contrary, under ER stress, levels of HERPUD1 increased rapidly due to a blockage in its proteasomal degradation. Thus, we explored whether HERPUD1 stability could work as a negative regulator of autophagy. In this work, we expressed a version of HERPUD1 with its ubiquitin-like domain (UBL) deleted, which is known to be crucial for its proteasome degradation. In comparison to HERPUD1-WT, we found the UBL-deleted version caused a negative role on basal and induced macroautophagy. Unexpectedly, we found stabilized HERPUD1 promotes ER remodeling independent of unfolded protein response activation observing an increase in stacked-tubular structures resembling previously described tubular ER rearrangements. Importantly, a phosphomimetic S59D mutation within the UBL mimics the phenotype observed with the UBL-deleted version including an increase in HERPUD1 stability and ER remodeling together with a negative role on autophagy. Moreover, we found UBL-deleted version and HERPUD1-S59D trigger an increase in cellular size, whereas HERPUD1-S59D also causes an increased in nuclear size. Interestingly, ER remodeling by the deletion of the UBL and the phosphomimetic S59D version led to an increase in the number and function of lysosomes. In addition, the UBL-deleted version and phosphomimetic S59D version established a tight ER-lysosomal network with the presence of extended patches of ER-lysosomal membrane-contact sites condition that reveals an increase of cell survival under stress conditions. Altogether, we propose stabilized HERPUD1 downregulates macroautophagy favoring instead a closed interplay between the ER and lysosomes with consequences in drug-cell stress survival

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Planes y programas de formación profesional : técnicos administrativos relaciones industriales

Se presentan los Planes y programas de formación para técnicos administrativos en relaciones industriales aplicable al año de 1983 en el que se describe el itinerario de formación, módulos ocupacionales, módulos instruccionales, objetivos, requisitos, intensidad horaria y operaciones que aplican.Training plans and programs for administrative technicians in industrial relations applicable to the year 1983 are described, describing the training itinerary, occupational modules, instructional modules, objectives, requirements, time intensity and operations that apply.Resumen del trabajo -- Itinerario de formación -- Resolución de módulos ocupacionales -- Guía de utilización del itinerario de formación -- Perfil profesional -- Plan de estudios para promoción -- Módulos ocupacionales -- Administración empresarial básica -- Nómina -- Análisis ocupacional y estudio del trabajo -- Selección y contratación de personal -- Evaluación, capacitación y desarrollo -- Salarios -- Seguridad industrial y bienestarna152 página

Planes y programas de formación profesional : técnicos administrativos mercadotecnia

Se describen los planes y programas para la familia ocupacional “Técnicos Administrativos de Mercadotecnia”, se resume el estudio de trabajo, itinerario de formación, módulos ocupacionales, módulos instruccionales, salidas ocupacionales, perfil profesional, requisitos y componentes de los módulos.The plans and programs for the occupational family “Marketing Administrative Technicians” are described, the work study, training itinerary, occupational modules, instructional modules, occupational exits, professional profile, requirements and module components are summarized.Resumen del trabajo página -- Itinerario de formación -- Relación de módulos ocupacionales -- Guía de utilización del itinerario de formación -- Perfil profesional -- Plan de estudios para promoción -- Módulos ocupacionales -- Administración empresarial básica -- Fundamentos de marketing. -- Análisis mercadológico y del producto -- Mershandising -- Administración y supervisión de ventas -- Dirección de ventas -- Investigación de mercados -- Investigación del producto -- Sistemas de compras -- Administración de activos -- Gestión de inventarios -- Promoción y exhibición -- Publicidadna196 página

Willingness-to-pay for COVID-19 vaccine in ten low-middle-income countries in Asia, Africa and South America: A cross-sectional study

Vaccine hesitancy is considered as one of the greatest challenges to control the ongoing coronavirus disease 2019 (COVID-19) pandemic. A related challenge is the unwillingness of the general public to pay for vaccination. The objective of this study was to determine willingness-to-pay (WTP) for COVID-19 vaccine among individuals from ten low-middle-income countries (LMICs) in Asia, Africa, and South America. Data were collected using an online questionnaire distributed during February - May 2021 in ten LMICs (Bangladesh, Brazil, Chile, Egypt, India, Iran, Nigeria, Pakistan, Sudan, and Tunisia). The major response variable of in this study was WTP for a COVID-19 vaccine. The assessment of COVID-19 vaccine hesitancy was based on items adopted from the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) vaccine hesitancy scale constructs. In this study, 1337 respondents included in the final analysis where the highest number of respondents was from India, while the lowest number was from Egypt. A total of 88.9% (1188/1337) respondents were willing to pay for the COVID-19 vaccination, and 11.1% (149/1337) were not. The average WTP for COVID-19 vaccination was 87.9 US dollars ($), (range:$5-$200). The multivariate model analysis showed that the country, monthly household income, having a history of respiratory disease, the agreement that routine vaccines recommended by health workers are beneficial and having received the flu vaccination within the previous 12 months were strongly associated with the WTP. Based on the country of origin, the highest mean WTP for COVID-19 vaccine was reported in Chile, while the lowest mean WTP for the vaccine was seen among the respondents from Sudan. The availability of free COVID-19 vaccination services appears as a top priority in the LMICs for successful control of the ongoing pandemic. This is particularly important for individuals of a lower socio-economic status. The effects of complacency regarding COVID-19 extends beyond vaccine hesitancy to involve less willingness to pay for COVID-19 vaccine and a lower value of WTP for the vaccine

Willingness-to-pay for COVID-19 vaccine in ten low-middle-income countries in Asia, Africa and South America: A cross-sectional study

Vaccine hesitancy is considered as one of the greatest challenges to control the ongoing coronavirus disease 2019 (COVID-19) pandemic. A related challenge is the unwillingness of the general public to pay for vaccination. The objective of this study was to determine willingness-to-pay (WTP) for COVID-19 vaccine among individuals from ten low-middle-income countries (LMICs) in Asia, Africa, and South America. Data were collected using an online questionnaire distributed during February - May 2021 in ten LMICs (Bangladesh, Brazil, Chile, Egypt, India, Iran, Nigeria, Pakistan, Sudan, and Tunisia). The major response variable of in this study was WTP for a COVID-19 vaccine. The assessment of COVID-19 vaccine hesitancy was based on items adopted from the World Health Organization (WHO) Strategic Advisory Group of Experts (SAGE) vaccine hesitancy scale constructs. In this study, 1337 respondents included in the final analysis where the highest number of respondents was from India, while the lowest number was from Egypt. A total of 88.9% (1188/1337) respondents were willing to pay for the COVID-19 vaccination, and 11.1% (149/1337) were not. The average WTP for COVID-19 vaccination was 87.9 US dollars ($), (range:$5-$200). The multivariate model analysis showed that the country, monthly household income, having a history of respiratory disease, the agreement that routine vaccines recommended by health workers are beneficial and having received the flu vaccination within the previous 12 months were strongly associated with the WTP. Based on the country of origin, the highest mean WTP for COVID-19 vaccine was reported in Chile, while the lowest mean WTP for the vaccine was seen among the respondents from Sudan. The availability of free COVID-19 vaccination services appears as a top priority in the LMICs for successful control of the ongoing pandemic. This is particularly important for individuals of a lower socio-economic status. The effects of complacency regarding COVID-19 extends beyond vaccine hesitancy to involve less willingness to pay for COVID-19 vaccine and a lower value of WTP for the vaccine

100 Cartas para Paulo Freire de quienes pretendemos Enseñar

Realizar un texto colectivo como “100 Cartas para Paule Freire de quienes pretendemos Enseñar”, es un desafío al reunir el aprehender desde el sentido profesional de la educación y con el espíritu de transformación, desde la educación como un espacio endógeno de revolución y exógeno a las comunidades y sociedades, en busca de un sentido de identidad. Hoy desde una crítica decolonial, antirracista, feminista y ecologica en la construcción de un sentido real que busque enfrentar el sistema hegemónico y destructivo que se ha impuesto con explotación, sangre y libertades de nuestro pueblo

New insights into the genetic etiology of Alzheimer’s disease and related dementias

Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele