Parámetros, correlaciones y tendencias genéticas de caracteres reproductivos en ganado Holstein de México

The objective was to calculate the parameters, correlations and describe the genetic trends of reproductive traits in Holstein cattle from Mexico in three different periods of time, in females born between 2006 and 2019, using records of the Mexican Holstein association. The reproductive parameters calculated were: calving to first insemination interval (CFI), number of services per conception (NSC), days open (DO), interval between calving (IBC), and age at first calving (AFC). The components of variance were estimated using restricted maximum likelihood in an animal model, to calculate genetic parameters (narrow-sense heritability (h2), repeatability (r) and genetic correlations) and phenotypic correlations. Additive genetic variances and genetic values were also estimated in three periods of time (P1: 2006-2009, P2: 2010-2013 and P3: 2014-2017). The calculated heritabilities were from 4 to 9 % and the repeatabilities from 8 to 9 %, values close to previous reports for fertility traits. Phenotypic correlations were positive for almost all reproductive parameters and genetic correlations were positive over a wide range (0.13-0.99). Analyses by period showed changes, possibly derived from the influence of the import and use of germplasm from foreign bulls (mainly from the United States of America and Canada) which implement genomic selection and include fertility traits. The present research has made it possible to update the information on reproductive and genetic parameters in fertility traits that can be incorporated into national genetic evaluations.El objetivo fue calcular los parámetros, correlaciones y describir las tendencias genéticas de caracteres reproductivos en ganado Holstein de México en tres periodos diferentes de tiempo, en hembras nacidas entre 2006 y 2019, usando registros de la asociación Holstein de México. Los parámetros reproductivos calculados fueron: intervalo parto a primer servicio (IPPS), el número de servicios por concepción (NSC), los días abiertos (DAB), el intervalo entre partos (IEP) y la edad al primer parto (EPP). Los componentes de la varianza fueron estimados utilizando máxima verosimilitud restringida en un modelo animal, para calcular parámetros genéticos (heredabilidad en sentido estricto (h2), repetibilidad (r) y correlaciones genéticas) y correlaciones fenotípicas. También se estimaron varianzas genéticas aditivas y valores genéticos en tres periodos de tiempo (P1: 2006-2009, P2: 2010-2013 y P3: 2014-2017). Las heredabilidades calculadas fueron de 4 a 9 % y las repetibilidades del 8 al 9 %, valores cercanos a reportes previos para características de fertilidad. Las correlaciones fenotípicas fueron positivas para casi todos los parámetros reproductivos y las genéticas fueron positivas en un rango amplio (0.13-0.99). Los análisis por periodos mostraron cambios, posiblemente derivados de la influencia de la importación y uso de germoplasma de toros extranjeros (principalmente de los Estados Unido de América y Canadá) que implementan selección genómica e incluyen características fertilidad. La presente investigación ha permitido actualizar la información de parámetros reproductivos y genéticos en caracteres de fertilidad que podrán ser incorporados a las evaluaciones genéticas nacionales

Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly

Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported. To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history. Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101) mutations. The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics. The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test. In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed. One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled. The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective. These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained. In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations

Normas de bioseguridad y seguridad laboral en Facultades de Ciencias Veterinarias de Argentina

The biosafety and labor constitute topics of fundamental importance in the exercise of the veterinary profession. Having as objectives to know the situation of teaching of this topic, application of the corresponding norms as likewise to promote the establishment of programs that you/they improve the before mentioned. They were taken to end interviews and surveys to authorities, educational, students and not educational of all the national abilities of veterinary science of Argentina. They were obtained as results that none of the abilities possesses an established program as such that single 3 abilities have conformed biosafety commissions and labor security. He/she has been that the classes with better demand level toward the students and application of the norms are Microbiology, Virology, Illness Infectious and Parasitology. Most of the interviewed abilities don't include in their budget the provision of elements and/or protection teams for the personnel. In the formation of the veterinary doctor's grade it should have a deep knowledge of this problem in order to assure a good quality of professional lifeLa bioseguridad y seguridad laboral constituyen temas de fundamental importancia en la docencia y en el ejercicio de la profesión veterinaria. El presente trabajo tiene como objetivos conocer la situación de la enseñanza de este tema en distintas Universidades, la aplicación de normas de bioseguridad en la etapa formativa y promover el establecimiento de programas específicos de bioseguridad. Para ello se llevaron a cabo entrevistas y encuestas a autoridades universitarias, docentes, estudiantes y no docentes de todas las Facultades de Veterinaria de Argentina. El análisis de la información indicó que ninguna de las facultades posee un programa establecido como tal y sólo tres Facultades han conformado comisiones de bioseguridad y seguridad laboral. Las Cátedras con mejor nivel de exigencia hacia los alumnos y aplicación de normas son Microbiología, Virología, Enfermedades Infecciosas y Parasitología. La mayoría de las Facultades encuestadas no incluyen en su presupuesto la provisión sistematizada de elementos y/o equipos de protección para el personal. Se discute la necesidad que en la formación de grado del Médico Veterinario se genere conciencia y conocimiento de los riesgos del ejercicios de la profesión a fin de asegurar una buena calidad de vida profesiona

Análisis de la experiencia del usuario en la plataforma web para la compra de calzado deportivo en Runa Store

La presente investigación tiene como objetivo evaluar la experiencia del usuario en la plataforma web de comercio electrónico de la marca Runa Store a partir del modelo explicativo de experiencia de compra web de López (2015), modelo centrado específicamente en el sector de moda. Runa Store, sujeto de estudio, presenta un bajo nivel de ventas a través de su plataforma web, lo cual representa un problema para la organización y, de esta forma, resulta importante el análisis de la plataforma para generar información relevante sobre la situación actual. Así, prioriza acciones de marketing enfocadas en mejorar su imagen; entre ellas, las remodelaciones de las tiendas físicas y la creación de su página web. Sin embargo, en esta última no se obtuvieron los resultados esperados y la hipótesis de los investigadores es que se explique por la falta de incorporar criterios de experiencia de compra de usuario. Así, existe un relevante sustento teórico que argumenta que la experiencia que el usuario recibe influye en la decisión de compra de un producto y/o servicio a través de la web. Más aún, existen distintas variables de la experiencia web que permiten su evaluación como el modelo propuesto por López de experiencia de compra online de moda. Previo al análisis, se realizó una recolección de datos a través de un conjunto de entrevistas a personas claves de la organización sobre la gestión del canal online de la marca para el mejor conocimiento de los esfuerzos realizados en dicha plataforma. Luego, se realizaron encuestas estructuradas a clientes potenciales de Runa Store para conocer y analizar la experiencia recibida en la página web. Por último, se llevaron a cabo entrevistas a expertos en herramientas y análisis cuantitativo con el fin de obtener su punto de vista sobre cómo abordar la evaluación del problema encontrado y recibir retroalimentación sobre el análisis realizado bajo las ecuaciones estructurales con el modelo elegido. Dicho modelo de López propone que determinadas características de la página web producen, a través de ciertos mediadores, respuestas en los usuarios en torno a la experiencia que reciben. Así, como aporte a la literatura y futuras investigaciones, se encontró como resultado del análisis la aplicabilidad del modelo mediante la experiencia evaluada en el usuario durante la compra de calzado deportivo en la empresa, provocando como consecuencia las variables satisfacción y lealtad. Sin embargo, también se demostró la no relación de la variable “demostrabilidad” hacia “control percibido”, “atención al cliente” hacia “control percibido”, “estética general” hacia “nivel de implicación afectiva”, “calidad” hacia “nivel de implicación afectiva” y “nivel de implicación afectiva” hacia “satisfacción”.Tesi

Gene expression profiles induced by E6 from non-European HPV18 variants reveals a differential activation on cellular processes driving to carcinogenesis

AbstractCervical cancer in developed countries remains as a major concern on public health policies due to incidence and mortality rates. Persistent infection with high risk human papillomavirus is a necessary etiological agent in the progression to invasive cervical carcinoma. A proposed hypothesis is the association between more aggressive HPV variants and the risk to develop cervical cancer. In order to have a global perspective in terms of cellular transcripts and molecular pathways affected by HPV18 E6 intratype variants; we conducted a genome wide analysis of gene expression. Our results show that E6 derived from non-European variants are able to up-regulate cellular transcripts associated to the hallmarks of cancer; such as cell cycle, migration, Wnt pathway and mTor signaling. Moreover, we were able to show that HPV18 E6 from African variant had a major effect on cellular processes such as cell cycle and migration as confirmed by functional studies

Oxygen: From Toxic Waste to Optimal (Toxic) Fuel of Life

Some 2.5 billion years ago, the great oxygenation event (GOE) led to a 105‐fold rise in atmospheric oxygen [O2], killing most species on Earth. In spite of the tendency to produce toxic reactive oxygen species (ROS), the highly exergonic reduction of O2 made it the ideal biological electron acceptor. During aerobic metabolism, O2 is reduced to water liberating energy, which is coupled to adenosine triphosphate (ATP) synthesis. Today, all organisms either aerobic or not need to deal with O2 toxicity. O2‐permeant organisms need to seek adequate [O2], for example, aquatic crustaceans bury themselves in the sea bottom where O2 is scarce. Also, the intestinal lumen and cytoplasm of eukaryotes is a microaerobic environment where many facultative bacteria or intracellular symbionts hide from oxygen. Organisms such as plants, fish, reptiles and mammals developed O2‐impermeable epithelia, plus specialized external respiratory systems in combination with O2‐binding proteins such as hemoglobin or leg‐hemoglobin control [O2] in tissues. Inside the cell, ROS production is prevented by rapid O2 consumption during the oxidative phosphorylation (OxPhos) of ATP. When ATP is in excess, OxPhos becomes uncoupled in an effort to continue eliminating O2. Branched respiratory chains, unspecific pores and uncoupling proteins (UCPs) uncouple OxPhos. One last line of resistance against ROS is deactivation by enzymes such as super oxide dismutase and catalase. Aerobic organisms profit from the high energy released by the reduction of O2, while at the same time they need to avoid the toxicity of ROS

Diversity of HLA Class I and Class II blocks and conserved extended haplotypes in Lacandon Mayans.

Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups). Distinctive alleles present in the Lacandon population include HLA-A*24:14 and HLA-B*40:08. Furthermore, in Lacandons we observed a high frequency of haplotypes containing the allele HLA-DRB1*04:11, a relatively frequent allele in comparison with other neighboring indigenous groups. The specific demographic history of the Lacandon population including inbreeding, as well as pathogen selection, may have elevated the frequencies of a small number of HLA class II alleles and DNA blocks. To assess the possible role of different selective pressures in determining Native American HLA diversity, we evaluated the relationship between genetic diversity at HLA-A, HLA-B and HLA-DRB1 and pathogen richness for a global dataset and for Native American populations alone. In keeping with previous studies of such relationships we included distance from Africa as a covariate. After correction for multiple comparisons we did not find any significant relationship between pathogen diversity and HLA genetic diversity (as measured by polymorphism information content) in either our global dataset or the Native American subset of the dataset. We found the expected negative relationship between genetic diversity and distance from Africa in the global dataset, but no relationship between HLA genetic diversity and distance from Africa when Native American populations were considered alone

Prior drug allergies are associated with worse outcome in patients with idiosyncratic drug-induced liver injury: A machine learning approach for risk stratification

The impact of prior drug allergies (PDA) on the clinical features and outcomes of patients who develop idiosyncratic drug-induced liver injury (DILI) is largely unknown. We aimed to assess the clinical presentation and outcomes of DILI patients based on the presence or absence of PDA and explore the association between culprit drugs responsible for DILI and allergy. We analysed a well-vetted cohort of DILI cases enrolled from the Spanish DILI Registry. Bootstrap-enhanced least absolute shrinkage operator procedure was used in variable selection, and a multivariable logistic model was fitted to predict poor outcomes in DILI. Of 912 cases with a first episode of DILI, 61 (6.7%) had documented PDA. Patients with PDA were older (p = 0.009), had higher aspartate aminotransferase (AST) levels (p = 0.047), lower platelet count (p = 0.011) and higher liver-related mortality than those without a history of drug allergies (11% vs. 1.6%, p < 0.001). Penicillin was the most common drug associated with PDA in DILI patients (32%). A model including PDA, nR-based type of liver injury, female sex, AST, total bilirubin, and platelet count showed an excellent performance in predicting poor outcome in patients from the Spanish DILI Registry (area under the ROC curve [AUC] 0.887; 95% confidence interval [CI] 0.794 – 0.981) and the LATINDILI Network (AUC 0.932; 95% CI 0.884 – 0.981). Patients with suspected DILI should be screened for PDA as they would require a close monitoring for early detection of worsening clinical course.Funding for open access charge: Universidad de Málaga/CBUA. This work was supported by grants of Instituto de Salud Carlos III (ISCIII), cofounded by Fondo Europeo de Desarrollo Regional – FEDER, cofounded by European Union (grant number PI21/01248), and by the Agencia Española de Medicamentos y Productos Sanitarios. CIBERehd is funded by ISCIII. HN holds a postdoctoral research contract funded by Junta de Andalucía (POSTDOC_21_00780). JSC holds a Juan Rodés contract (JR21/00066), JMP-B holds a Rio Hortega contract (CM21/00074), and IAA holds a Sara Borrell contract (CD20/00083), funded by ISCIII. This project has received funding from the European Horizon´s research and innovation program HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679. Open Access funding provided thanks to the CRUE-CSIC agreement with Elsevier

The MADS-box XAANTAL1 increases proliferation at the Arabidopsis root stem-cell niche and participates in transition to differentiation by regulating cell-cycle components

Background Morphogenesis depends on the concerted modulation of cell proliferation and differentiation. Such modulation is dynamically adjusted in response to various external and internal signals via complex transcriptional regulatory networks that mediate between such signals and regulation of cell-cycle and cellular responses (proliferation, growth, differentiation). In plants, which are sessile, the proliferation/differentiation balance is plastically adjusted during their life cycle and transcriptional networks are important in this process. MADS-box genes are key developmental regulators in eukaryotes, but their role in cell proliferation and differentiation modulation in plants remains poorly studied. Methods We characterize the XAL1 loss-of-function xal1-2 allele and overexpression lines using quantitative cellular and cytometry analyses to explore its role in cell cycle, proliferation, stem-cell patterning and transition to differentiation. We used quantitative PCR and cellular markers to explore if XAL1 regulates cell-cycle components and PLETHORA1 (PLT1) gene expression, as well as confocal microscopy to analyse stem-cell niche organization. Key Results We previously showed that XAANTAL1 (XAL1/AGL12) is necessary for Arabidopsis root development as a promoter of cell proliferation in the root apical meristem. Here, we demonstrate that XAL1 positively regulates the expression of PLT1 and important components of the cell cycle: CYCD3;1, CYCA2;3, CYCB1;1, CDKB1;1 and CDT1a. In addition, we show that xal1-2 mutant plants have a premature transition to differentiation with root hairs appearing closer to the root tip, while endoreplication in these plants is partially compromised. Coincidently, the final size of cortex cells in the mutant is shorter than wild-type cells. Finally, XAL1 overexpression-lines corroborate that this transcription factor is able to promote cell proliferation at the stem-cell niche. ConclusionXAL1 seems to be an important component of the networks that modulate cell proliferation/differentiation transition and stem-cell proliferation during Arabidopsis root development; it also regulates several cell-cycle components.This work constitutes a partial fulfilment of the Graduate Program ‘Doctorado en Ciencias Biomédicas’ of the Universidad Nacional Autónoma de México in which Karla V. García-Cruz developed this project. We acknowledge the Consejo Nacional de Ciencia y Tecnología (CONACYT, México) that provided her scholarship. This work was supported by CONACYT: 240180 and 180380; PAPIIT, UNAM: IN203214-3; IN203113-3; IN203814-3; IN211516 and BFU2012-34821 from MINECO (Spain) to C.G., and an institutional grant from Fundación Ramón Areces to Centro de Biología Molecular Severo Ochoa. We thank David Cruz Sánchez and Diana Romo for technical and logistical support, respectively.Peer reviewe