Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility

Versión Open Access de la web de la revistaBackground: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation, Grant/Award Number: SAF2016-78722-R;PID2020-120157RB-I00; Instituto de Salud Carlos III, Grant/Award Number: DTS18/00101; Generalitat de Catalunya, Grant/Award Number: 2017SGR191; Ramón y Cajal, Grant/Award Number: RYC-2014-16458; Juan de la Cierva Incorporación, Grant/Award Number: IJC2018-038026-I; Andalusian Government, Grant/Award Number: PY20_00212;B-CTS-584-UGR20; FCT post-doctoral fellowship, Grant/Award Number: SFRH/BPD/120777/2016; FCT/MCTES, Grant/Award Numbers: UID/BIM/00009/2016, UIDB/00009/2020; ISCIII SNS/Dpt. Salut Generalitat de Catalunya, Grant/Award Number: CES09/02

Non-classical circulating monocytes expressing high levels of microsomal prostaglandin E2 synthase-1 tag an aberrant IFN-response in systemic sclerosis

Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14+ PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14+ cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc.Funding for open access charge: Universidad de Granada / CBUA This work was supported by the grant P18-RT-4442 funded by Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía. “Red de Investigación Cooperativa Orientada a Resultados en Salud'' (RICOR, RD21/0002/003). 115565. LBC was supported by the Spanish Ministry of Science and Innovation through the Juan de la Cierva Incorporación' program (Grant ref. IJC2018-038026-I, funded by MCIN/AEI/10.13039/501,100,011,033), which includes FEDER funds. MAH is a recipient of a Miguel Servet fellowship (CP21/00132) from the Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation). GV-M was funded by the Grant PRE2019-087586 funded by MCIN/AEI/10.13039/501,100,011,033 and by “ESF Investing in your future”

Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort

Background: Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non-obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes). Objectives: The main objective of the present study is to analyze in the Iberian population the effect of 6 single-nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome-wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns. Materials and methods: We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS-associated variants PRMT6-rs12097821, PEX10-rs2477686, CDC42BPA-rs3000811, IL17A-rs13206743, ABLIM1-rs7099208, and SOX5-rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources. Results: ABLIM1-rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA-rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10-rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis-specific expression of nearby genes and that lincRNA may play a role in SpF. Conclusions: Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1-rs7099208, CDC42BPA-rs3000811, and PEX10-rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.We thank the National DNA Bank Carlos III (University of Salamanca, Spain) for supplying part of the control DNA samples from Spain, as well as all patients and controls for kindly agreeing to their essential collaboration. This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. SAF2016- 78722-R) the “Ramón y Cajal” program (ref. RYC-2014- 16458) and the “Juan de la Cierva Incorporación” program (ref. IJC2018- 038026-I), which include FEDER funds. AG-J was recipient of a grant from the "Plan Propio" program of the University of Granada ("Becas de Iniciación a la Investigación para estudiantes de Grado,” conv. 2019). SL received support from the Spanish Ministry of Science and Innovation (grants FIS-ISCIII DTS18/00101, co-funded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe) and from Generalitat de Catalunya (grant 2017SGR191). SL is sponsored by the “Researchers Consolidation Program” from the SNS-Dpt. Salut Generalitat de Catalunya (Exp. CES09/020). JG was partially funded by FCT/MCTES, through national funds attrib-uted to Center for Toxicogenomics and Human Health—ToxOmics (UIDB/00009/2020). PIM is supported by the FCT post-doctoral fel-lowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the Programa Operacional do Capital Humano

Confidence-Based Learning in Investment Analysis

The aim of this study is to determine the effectiveness of using multiple choice tests in subjects related to the administration and business management. To this end we used a multiple-choice test with specific questions to verify the extent of knowledge gained and the confidence and trust in the answers. The tests were performed in a group of 200 students at the bachelor's degree in Business Administration and Management. The analysis made have been implemented in one subject of the scope of investment analysis and measured the level of knowledge gained and the degree of trust and security in the responses at two different times of the course. The measurements have been taken into account different levels of difficulty in the questions asked and the time spent by students to complete the test. The results confirm that students are generally able to obtain more knowledge along the way and get increases in the degree of trust and confidence in the answers. It is confirmed as the difficulty level of the questions set a priori by the heads of the subjects are related to levels of security and confidence in the answers. It is estimated that the improvement in the skills learned is viewed favourably by businesses and are especially important for job placement of students

Metodología para selección tribológica de lubricantes para formado de cuerpos de aluminio

Los refrigerantes para el “formado de cuerpo” de latas de aluminio consisten de emulsiones de aceite en agua los cuales son utilizados como lubricantes en el proceso de planchado. Estos lubricantes se formulan para enfriar la interfase en el proceso de formación de la lata y proveer la lubricidad necesaria para el planchado. En el presente trabajo se presenta una nueva metodología para la selección de distintos refrigerantes para “formado de cuerpo” en función a su desempeño tribológico utilizando un tribómetro de confi guración espiga y bloque en V. Los resultados experimentales indican que la conductividad térmica de cada lubricante es un parámetro muy importante en su desempeño tribológico. Este método se aplica ya con éxito para evaluar y comparar el funcionamiento de refrigerantes comerciales para “formado de cuerpo” de latas de aluminio

NEW RECORD O? INCA CLATHRATA SOMMERI WESTWOOD (COLEOPTERA: MELOLONTHIDAE, THRICHIINAE) IN TAMAULIPAS, MEXICO

Se extiende la distribución conocida de Inca clathrata sommeri Westwood, 120 Km al Norte en el Estado de Tamaulipas, México, en donde habita en un bosque de encino situado a 1100 msnm

La organización de las mujeres en el Sindicato Nacional de Trabajadores de Agricultura y Recursos Hidráulicos (SNTAR)

Las luchas sindicales que han emprendido las trabajadoras de la SARH han sido, principalmente, de las madres y en momentos coyuntrales, con excepción de un movimiento fuerte que hubo en 1984 en Jalapa, Veracruz, donde las mujeres de esa sección se destacaron por su participación en todos los niveles para democratizar su sindicato. El CEN, conjuntamente con las autoridades estatales, reprimieron su movimiento y varas trabajadoras fueron despedidas y otras reubicada

Estrategias de política económica dirigidas al sector ganadero. 2010-2015

El objetivo del escrito es analizar los impactos sectoriales de las estrategias de política económica dirigidas al sector ganadero de Nicaragua. Así pues, para efectos de desarrollo del estudio investigativo se ha recurrido al método de análisis-síntesis que ha permitido observar, comprender, explicar y valorar las estrategias de política implementadas en el sector pecuario de Nicaragua entre 2010 y 2015. De ahí que se induzca que tales ordenanzas han logrado cumplir en gran medida los objetivos de crecimiento del sector e incremento de su productividad. No obstante, deben redirigirse acciones para dinamizar ciertas actividades pertenecientes al sector como la porcina, a la cual no se destinan recursos suficientes para su desarrollo. Paralelamente, cabe destacar el elevado potencial que representa este sector para contribuir a los Objetivos de Desarrollo Sostenible (ODS), por su incidencia en los sistemas alimentarios, económicos y ambientales; sin embargo, éste está siendo subutilizado. Por ello, se propone intervenir en los desafíos de la producción pecuaria e identificar nuevas herramientas y mejores políticas para el desarrollo de la ganadería sostenible en el territorio

La gestión del talento humano y la ventaja competitiva de la empresa CISESAC Chimbote 2017

En la presente investigación se analizó la gestión del talento humano la ventaja competitiva de la empresa Cisesac en Chimbote, 2017. Por medio de la aplicación de un cuestionario realizado y dirigido a 30 trabajadores como población de dicha institución y por medio de una ficha de evaluación los cuales permitieron analizar la gestión del talento humano y la ventaja competitiva. El diseño de la investigación fue no experimental ya que no tuvo manipulación de las variables y transversal porque se recolectaron datos en un solo momento. Fue Correlacional , ya que se busca la relación que existe entre ambas variables. En conclusión, como resultado se obtuvo que la Gestión del talento humano de la empresa Cisesac es regular con un 40% del personal encuestado, pese a lograr las metas, no tienen una buena orientación, no les gusta el control y además existen conflictos, mientras en la variable ventaja competitiva l se muestra que el 43% del personal tiene un nivel regular debido a que no consideran que la empresa tiene mucha competencia y que deberían realizar acciones que favorezcan al cliente