A evolução molecular do sistema da oxitocina em primatas

A oxitocina (OXT) é um nonapeptídio envolvido em um amplo espectro de funções fisiológicas e comportamentais. Até recentemente acreditava-se em uma conservação de milhões de anos da sequência de aminoácidos, levando a pensar numa única proteína para todos os mamíferos placentários. Neste estudo foi analisada a oxitocina de 29 espécies de primatas, e desse grupo, foram estudados também os receptores de oxitocina (OXTR) de 21 espécies. Registramos aqui uma quebra na linha de conservação descrevendo 3 novas formas de OXT em macacos do Novo Mundo e reportamos um aminoácido (OXT-8Pro) com seleção positiva na família Cebidae; essa mesma posição registrou uma significância estatística (p= 0.003), numa análise de correlação com o tamanho da ninhada. Reforçando essa correlação, descrevemos uma nova forma de OXT (OXT-3Val-8Pro) nos Saguinus (Cebidae), um gênero com um pronunciado cuidado parental dos machos aparentados ou não. Em OXTR também foram detectados aminoácidos sob seleção positiva, assim como processos de coevolução intramolecular e intermolecular com seu ligante, OXT. Com os resultados aqui obtidos, propomos possíveis cenários da interação dessas novas formas de OXT com seus receptores e propomos perspectivas para o estudo do sistema OXT-OXTR e sua relação com outros sistemas.Oxytocin (OXT) is a nonapeptide involved with a wide range of physiological and behavior functions. Until recently it was believed that an unmodified oxytocin sequence was present in all placental mammals. This study analyzed the oxytocin in 29 primate species, and the oxytocin receptor (OXTR) was also investigated in 21 of these species. We reported here an unprecedented lack of conservation, describing three novel OXT forms in the New World Monkeys. A signal of positive selection was detected in OXT- 8Pro in the Cebidae family and the same position showed a statistically significance (p= 0.003) correlation with litter size. Reinforcing this correlation, we describe here a novel OXT form (OXT-3Val- 8Pro) in Saguinus (Cebidae), a genus with a pronounced male parental care. In OXTR amino acids under positive selection as well as intramolecular and intermolecular coevolutionary process with his ligand, OXT, were detected. We suggest some interaction scenarios of the novel OXT forms with their receptors and we propose perspectives for the study of the OXT-OXTR system as well as its relationship with other systems

Propuesta de recuperación y adecuación de estibas en la empresa cerámica San Lorenzo

Generar la recuperación de las estibas donde se despacha el producto terminado generado en la planta para así generar un control de las estibas que se devuelvan a la planta para luego generar su validación y los procesos como son clasificación, reparación y almacenamiento para llevarnos a la reducción de costos en este insumo que es primordial en el desarrollo de la actividad económica de la empresa.Generate the recovery of the pallets where the finished product generated in the plant is dispatched in order to generate control of the pallets that are returned to the plant and then generate their validation and processes such as classification, repair and storage to lead to reduction of costs in this input that is essential in the development of the economic activity of the company

ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to the host-cell infection. We perform comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses to analyze in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors

ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS-CoV-2

The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites. A perfect scenario for natural selection favored this opportunistic new coronavirus in its trajectory of infecting humans. We suggest that SARS-CoV-2 became a specialist coronavirus for human hosts. Differences in the rate of infection and mortality could be related to the innate immune responses, other unknown genetic factors, as well as non-biological factors

INSTALACIÓN Y CONFIGURACIÓN DHCP SERVER, DNS SERVER Y CONTROLADOR DE DOMINIO, PROXY NO TRANSPARENTE, CORTAFUEGOS, SERVICIOS FILE SERVER, PRINT SERVER Y VPN

El presente documento se detalla, muestra y evidencia el proceso realizado en la instalación de los diferentes procesos de administración y control de red que permite el servidor Zentyal. En el cual se realizará la Instalación y configuración DHCP Server, DNS Server y Controlador de Dominio, También un Proxy no transparente, Cortafuegos, servicios File Server, Print Server y VPN. Todo lo anterior mencionado con la intensión de que, como grupo de trabajo, terminemos de dar solución a la problemática* de puesta en marcha una infraestructura de red de acuerdo a los servicios y requerimientos específicos solicitados por el clienteThis document details, shows and evidences the process carried out in the installation of the different network administration and control processes that the Zentyal server allows. In which the Installation and configuration of the DHCP Server, DNS Server and Domain Controller will be carried out, as well as a non-transparent Proxy, Firewall, File Server, Print Server and VPN services. All of the above mentioned with the intention that, as a working group, we finish solving the problem of setting up a network infrastructure according to the specific services and requirements requested by the client

Herramientas tecnológicas para la transformación pedagógica

27 cm.El presente libro es el segundo tomo de la serie que desarrolla un planteamiento frente a la práctica pedagógica de la investigación educativa interdisciplinar desde la transformación y el uso de tecnologías (provisional)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Boletín oficial de la provincia de Santander: Año XXVIII Número 52 - 1964 Abril 29

Um dos maiores desafios que as Ciências Biomédicas têm na atualidade é conseguir conectar variações em nível do genoma com aquelas observadas em nível de fenótipos. Utilizando a estratégia de genes candidatos e abordagens interdisciplinares, temos obtido sucesso nessa empreitada desafiadora, ajudando, inclusive, a quebrar paradigmas, pelo menos no que diz respeito a características táxon-específicas. Tivemos como foco os neuropeptídeos Oxitocina (OXT) e Vasopressina (AVP), dois neurohormônios parálogos que, ao interagirem com seus receptores (OXTR, AVPR1a, AVPR1b e AVPR2), promovem funções fisiológicas e comportamentais. Demonstramos que a postulada conservação da sequência de aminoácidos de OXT em todos os mamíferos placentários não se confirma, visto serem encontradas pelo menos 7 formas (Leu8OXT, Pro8OXT, Val3Pro8OXT, Ala8OXT, Thr8OXT, Phe2OXT e Val3OXT) em espécies de primatas do Novo Mundo (pNM). Conectamos, ainda, pelo menos algumas dessas variantes com traços complexos em clados de macacos do Novo Mundo, tal como parto gemelar, monogamia social e cuidado paterno, o que indica sua possível relevância evolutiva, detectada também por testes específicos para seleção positiva e coevolução entre ligante e receptor. Para avançar no conhecimento funcional das potencialmente adaptativas variantes, conduzimos testes e experimentos in silico, in vitro e in vivo, comparando-as com a forma mais comum de OXT (Leu8OXT) e AVP. Demonstramos a capacidade reduzida das variantes Cebidae Pro8OXT e Saguinus Val3Pro8OXT no recrutamento das β-arrestinas, com consequente impacto na internalização de receptores e na dessensibilização de todo o sistema OXT-AVP. Ainda, conseguimos avaliar a capacidade de ambas as variantes estimularem o cuidado paterno em ratos, mostrando, pela primeira vez, um modelo natural para o conceito de agonismo com seletividade funcional, com prováveis implicações evolutivas. Além disso, investigamos a região regulatória do gene OXTR e identificamos que o número de elementos de resposta de progesterona (PREs) no promotor do referido gene é significativamente correlacionado com a presença de cuidado paterno no clado dos pNM. Com isso, buscamos delinear um cenário completo sobre a emergência de fenótipos adaptativos em macacos do Novo Mundo.One of the greatest challenges that the Biomedical Sciences has at present is to be able to connect variations at genome level with those observed at phenotype level. Using the strategy of candidate genes and interdisciplinary approaches we have succeeded in this challenging endeavor and even helped to break paradigms, at least considering taxonspecific characteristics. We focused on the oxytocin (OXT) and Vasopressin (AVP) nonapeptides, two paralog neurohormones that interact with their receptors (OXTR, AVPR1a, AVPR1b and AVPR2) promoting physiological and behavioral functions. We demonstrated that the postulated conservation of the amino acid sequence of OXT in all placental mammals is not true since at least 7 forms (Leu8OXT, Pro8OXT, Val3Pro8OXT, Ala8OXT, Thr8OXT, Phe2OXT and Val3OXT) were found in New World primate species (NWm). We also connected at least some of these variants with complex features in clades of NWm, such as twin birth, social monogamy and paternal care, indicating their possible evolutionary relevance, also detected by specific tests for positive selection and co-evolution between ligand and receptor. To understand the functional knowledge of the potentially adaptive variants we conducted in silico, in vitro and in vivo tests and experiments comparing them with the most common form of OXT (Leu8OXT) and AVP. We demonstrated the reduced capacity of the Cebidae Pro8OXT and Saguinus Val3Pro8OXT variants in the recruitment of β-arrestins, with a consequent impact on receptor internalization and desensitisation of the entire OXTAVP system. Furthermore, we were able to evaluate the ability of both variants to stimulate paternal care in rats, showing, for the first time, a natural model for the concept of agonism with functional selectivity, with probable evolutionary implications. In addition, we investigated the regulatory region of the OXTR gene and identified that the number of progesterone response elements (PREs) in the promoter of the above mentioned gene is significantly correlated with the presence of parental care in the NWm clade. With this, we aimed to delineate a complete scenario on the emergence of adaptive phenotypes in the New World monkeys