Transactive Response DNA-Binding Protein (TARDBP/TDP-43) Regulates Cell Permissivity to HIV-1 Infection by Acting on HDAC6

The transactive response DNA-binding protein (TARDBP/TDP-43) influences the processing of diverse transcripts, including that of histone deacetylase 6 (HDAC6). Here, we assessed TDP-43 activity in terms of regulating CD4+ T-cell permissivity to HIV-1 infection. We observed that overexpression of wt-TDP-43 increased both mRNA and protein levels of HDAC6, resulting in impaired HIV-1 infection independently of the viral envelope glycoprotein complex (Env) tropism. Consistently, using an HIV-1 Env-mediated cell-to-cell fusion model, the overexpression of TDP-43 levels negatively affected viral Env fusion capacity. Silencing of endogenous TDP-43 significantly decreased HDAC6 levels and increased the fusogenic and infection activities of the HIV-1 Env. Using pseudovirus bearing primary viral Envs from HIV-1 individuals, overexpression of wt-TDP-43 strongly reduced the infection activity of Envs from viremic non-progressors (VNP) and rapid progressors (RP) patients down to the levels of the inefficient HIV-1 Envs observed in long-term non-progressor elite controllers (LTNP-EC). On the contrary, silencing endogenous TDP-43 significantly favored the infectivity of primary Envs from VNP and RP individuals, and notably increased the infection of those from LTNP-EC. Taken together, our results indicate that TDP-43 shapes cell permissivity to HIV-1 infection, affecting viral Env fusion and infection capacities by altering the HDAC6 levels and associated tubulin-deacetylase anti-HIV-1 activity.This work is supported by the Spanish AIDS network “Red Temática Cooperativa de Investigación en SIDA” RD12/0017/0002, RD12/0017/0028, RD12/0017/0034, RD16/0025/0011, RDCIII16/0002/0005 and RD16/0025/0041 as part of the Plan Nacional R + D+I and co-funded by the Spanish “Instituto de Salud Carlos III (ISCIII)-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER)”. J.B. is a researcher from “Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol” supported by the Health Department of the Catalonian Government/Generalitat de Catalunya and ISCIII grant numbers PI17/01318 and PI20/00093 (to J.B.). Work in CC Lab was supported by grants SAF (2010-17226) and (2016-77894-R) from MINECO (Spain), FIS (PI 13/02269, ISCIII) and PI20/00093. Work in CF Lab was supported by the Cabildo Insular de Tenerife (grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”); the agreement with the Instituto Tecnológico y de Energías Renovables (ITER) to strengthen scientific and technological education, training research, development and innovation in Genomics, Personalized Medicine and Biotechnology (grant number OA17/008). A.V.-F.’s Lab is supported by the European Regional Development Fund (ERDF), RTI2018-093747-B-100 (“Ministerio de Ciencia e Innovación”, Spain), “Ministerio de Ciencia, Innovación y Universidades” (Spain), ProID2020010093 (“Agencia Canaria de Investigación, Innovación y Sociedad de la Información” and European Social Fund), UNLL10-3E-783 (ERDF and “Fundación CajaCanarias”) and “SEGAI-ULL”. S.P-Y is funded by “Fundación Doctor Manuel Morales” (La Palma, Spain) and “Contrato Predoctoral Ministerio-ULL Formación de Doctores” (2019 Program) (“Ministerio de Ciencia, Innovación y Universidades”, Spain). R.C.-R. is funded by RD16/0025/0011 and ProID2020010093 (“Agencia Canaria de Investigación, Innovación y Sociedad de la Información” and European Social Fund). J.G.-L. is funded by the “Juan de la Cierva de Incorporación” Spanish Program (IJC2019-038902-I) (“Ayudas Juan de la Cierva de incorporación; Agencia Estatal de Investigación. Ministerio de Ciencia e Innovación”).S

The rs12617336 and rs17574 Dipeptidyl Peptidase-4 Polymorphisms Are Associated With Hypoalphalipoproteinemia and Dipeptidyl Peptidase-4 Serum Levels: A Case-Control Study of the Genetics of Atherosclerotic Disease (GEA) Cohort

Dipeptidyl peptidase-4 (DPP4) can influence lipid homeostasis and atherosclerosis progression. We aimed to assess the association of DPP4 gene polymorphisms with hypoalphalipoproteinemia and DPP4 serum levels, in a cohort of Mexican individuals. Five DPP4 polymorphisms (rs12617336, rs12617656, rs1558957, and rs3788979, and rs17574) were genotyped in 748 participants with and 745 without hypoalphalipoproteinemia. The associations were evaluated using logistic regression analyses. Under inheritance models adjusted for confounding variables, the rs12617336 (OR = 0.22, Pheterozygote = 0.001) and rs17574 (OR = 0.78, Padditive = 0.022; OR = 0.73, Pdominant = 0.012; OR = 0.73, Pheterozygote = 0.017; OR = 0.72, Pcodominant1 = 0.014) minor alleles were associated with a low risk of hypoalphalipoproteinemia. After the correction for multiple comparisons, the associations were marginal except the association of the rs12617336 that remaining significant. Additionally, both DPP4 minor alleles were associated with protection for the presence of insulin resistance (IR) (OR = 0.17, Pheterozygote = 0.019 for rs12617336 and OR = 0.75, Padditive = 0.049 for rs17574). The rs12617336 minor allele was also associated with a low risk of hyperinsulinemia (OR = 0.11, Pheterozygote = 0.006). Differences in DPP4 levels were observed in individuals with rs17574 genotypes, the rs17574 GG genotype individuals had the lowest levels. Our data suggest that rs12617336 and rs17574 DPP4 minor alleles could be envisaged as protective genetic markers for hypoalphalipoproteinemia, IR, and hyperinsulinemia. The rs17574 GG genotype was associated with the lowest DPP4 levels

Factor structure and measurement invariance across various demographic groups and over time for the phq-9 in primary care patients in spain

The Patient Health Questionnaire (PHQ-9) is a widely-used screening tool for depression in primary care settings. The purpose of the present study is to identify the factor structure of the PHQ-9 and to examine the measurement invariance of this instrument across different sociodemographic groups and over time in a sample of primary care patients in Spain. Data came from 836 primary care patients enrolled in a randomized controlled trial (PsicAP study) and a subsample of 218 patients who participated in a follow-up assessment at 3 months. Confirmatory factor analysis (CFA) was used to test one- and two-factor structures identified in previous studies. Analyses of multiple-group invariance were conducted to determine the extent to which the factor structure is comparable across various demo- graphic groups (i.e., gender, age, marital status, level of education, and employment situa- tion) and over time. Both one-factor and two-factor re-specified models met all the pre- established fit criteria. However, because the factors identified in the two-factor model were highly correlated (r = .86), the one-factor model was preferred for its parsimony. Multi-group CFA indicated measurement invariance across different demographic groups and across time. The present findings suggest that physicians in Spain can use the PHQ-9 to obtain a global score for depression severity in different demographic groups and to reliably monitor changes over time in the primary care setting

The Research Journey as a Challenge Towards New Trends

The academic community of the department of Risaralda, in its permanent interest in evidencing the results of the research processes that are carried out from the Higher Education Institutions and as a product of the VI meeting of researchers of the department of Risaralda held in November 2021 presents its work: “The journey of research as a challenge towards new trends”, which reflects the result of the latest research and advances in different lines of knowledge in Agricultural Sciences, Health Sciences, Social Sciences and Technology and Information Sciences, which seek to solve and meet the demands of the different sectors. This work would not have been possible without the help of each of the teachers, researchers and authors who presented their articles that make up each of the chapters of the book, to them our gratitude for their commitment, dedication and commitment, since their sole purpose is to contribute from the academy and science to scientific and technological development in the search for the solution of problems and thus contribute to transform the reality of our society and communities. We also wish to extend our gratitude to the institutions of the Network that made this publication possible: UTP, UCP, UNAD, UNIREMINGTON; UNISARC, CIAF, Universidad Libre, Uniclaretiana, Fundación Universitaria Comfamiliar and UNIMINUTO, institutions that in one way or another allowed this work to become a reality, which we hope will be of interest to you.Preface............................................................................................................................7 Chapter 1. Technologies and Engineering Towards a humanization in Engineering using soft skills in training in Engineers.............................................................................................................11 Omar Iván Trejos Buriticá1, Luis Eduardo Muñoz Guerrero Innovative materials in construction: review from a bibliometric analysis....................................................................................................................27 Cristian Osorio Gómez, Daniel Aristizábal Torres, Alejandro Alzate Buitrago, Cristhian Camilo Amariles López Bibliometric review of disaster risk management: progress, trends, and challenges.........................................................................................................51 Alejandro Alzate Buitrago, Gloria Milena Molina Vinasco. Incidence of land coverage and geology, in the unstability of lands of the micro-basin of the Combia creek, Pereira, Risaralda....................................73 Alejandro Alzate Buitrago, Daniel Aristizábal Torres. Chapter 2. Arts, Humanities, and Social Sciences Training experience with teachers teaching mathematics using the inquiry methodology ...............................................................................................95 Vivian Libeth Uzuriaga López, Héctor Gerardo Sánchez Bedoya. Interpretation of the multiple representations of the fears associated to the boarding of limited visual patients in the elective I students’ written productions and low vision ...................................................................................113 Eliana Bermúdez Cardona, Ana María Agudelo Guevara, Caterine Villamarín Acosta. The relevance of local knowledge in social sciences............................................131 Alberto Antonio Berón Ospina, Isabel Cristina Castillo Quintero. Basic education students’ conceptions of conflict a view from the peace for the education....................................................................................................143 Astrid Milena Calderón Cárdenas,Carolina Aguirre Arias, Carolina Franco Ossa, Martha Cecilia Gutiérrez Giraldo, Orfa Buitrago. Comprehensive risk prevention in educational settings: an interdisciplinary and socio-educational approach ............................................................................163 Olga María Henao Trujillo, Claudia María López Ortiz. Chapter 3. Natural and Agricultural Sciences Physicochemical characterization of three substrates used in the deep bedding system in swine .......................................................................................175 Juan Manuel Sánchez Rubio, Andrés Felipe Arias Roldan, Jesús Arturo Rincón Sanz, Jaime Andrés Betancourt Vásquez. Periodic solutions in AFM models........................................................................187 Daniel Cortés Zapata, Alexander Gutiérrez Gutiérrez. Phenology in flower and fruit of Rubus glaucus benth. Cv. Thornless in Risaralda: elements for phytosanitary management .........................................199 Shirley Palacios Castro, Andrés Alfonso Patiño Martínez, James Montoya Lerma, Ricardo Flórez, Harry Josué Pérez. Socio-economic and technical characterization of the cultivation of avocado (Persea americana) in Risaralda..............................................................217 Andrés Alfonso Patiño Martínez, Kelly Saudith Castañez Poveda, Eliana Gómez Correa. Biosecurity management in backyard systems in Santa Rosa de Cabal, Risaralda................................................................................................................227 Julia Victoria Arredondo Botero, Jaiver Estiben Ocampo Jaramillo, Juan Sebastián Mera Vallejo, Álvaro de Jesús Aranzazu Hernández. CONTENTS Physical-chemical diagnosis of soils in hillside areas with predominance of Lulo CV. La Selva production system in the department of Risaralda.............241 Adriana Patricia Restrepo Gallón, María Paula Landinez Montes, Jimena Tobón López. Digestibility of three concentrates used in canine feeding....................................271 María Fernanda Mejía Silva, Valentina Noreña Sánchez, Gastón Adolfo Castaño Jiménez. Chapter 4. Economic, Administrative, and Accounting Sciences Financial inclusion in households from socioeconomic strata 1 and 2 in the city of Pereira ..................................................................................................285 Lindy Neth Perea Mosquera, Marlen Isabel Redondo Ramírez, Angélica Viviana Morales. Internal marketing strategies as a competitive advantage for the company Mobilautos SAS de Dosquebradas........................................................................303 Inés Montoya Sánchez, Sandra Patricia Viana Bolaños, Ana María Barrera Rodríguez. Uses of tourist marketing in the tourist sector of the municipality of Belén de Umbría, Risaralda.............................................................................................319 Ana María Barrera Rodríguez, Paola Andrea Echeverri Gutiérrez, María Camila Parra Buitrago, Paola Andrea Martín Muñoz, Angy Paola Ángel Vélez, Luisa Natalia Trejos Ospina. Territorial prospective of Risaralda department (Colombia), based on the SDGS...............................................................................................................333 Juan Guillermo Gil García, Samanta Londoño Velásquez. Chapter 5. Health and Sports Sciences Performance evaluation in times of pandemic. What do medical students think?.......................................................................................................353 Samuel Eduardo Trujillo Henao, Rodolfo A. Cabrales Vega, Germán Alberto Moreno Gómez. The relevance of the therapist’s self and self-reference in the training of psychologists.....................................................................................................371 Maria Paula Marmolejo Lozano, Mireya Ospina Botero. Habits related to oral health which influence lifestyle of elder people in a wellness center for the elderly in Pereira 2020. .............................................387 Isadora Blanco Pérez, Olga Patricia Ramírez Rodríguez, Ángela María Rincón Hurtado. Analysis of the suicide trend in the Coffee Region in Colombia during the years 2012-2018 ..............................................................................................405 Germán Alberto Moreno Gómez, Jennifer Nessim Salazar, Jairo Franco Londoño, Juan Carlos Medina Osorio. Hind limb long bone fractures in canines and felines...........................................419 María Camila Cruz Vélez, Valentina Herrera Morales, Alba Nydia Restrepo Jiménez, Lina Marcela Palomino, Gabriel Rodolfo Izquierdo Bravo. Prevalence of overweight and obesity in children in the rural and urban area of Risaralda....................................................................................................439 Angela María Álvarez López, Angela Liceth Pérez Rendón, Alejandro Gómez Rodas, Luis Enrique Isaza Velásquez. Chapter 6. Architecture, Design and Advertising The artisan crafts of Risaralda, characteristics, importance, and risks within the Colombian Coffee Cultural Landscape, CCCL....................................457 Yaffa Nahir Ivette Gómez Barrera, Javier Alfonso López Morales

Problema de localización y ruteo en ambientes de ultima Milla.

El transporte de mercancías es fundamental en la actividad de una empresa, puesto que es transversal a las operaciones de la misma, desde el recibo de materia prima hasta la distribución del producto terminado, ya sea de manera directa o indirecta al cliente, se evidencia como el transporte es piedra angular en cualquier tipo de empresa..

From Samples to Germline and Somatic Sequence Variation: A Focus on Next-Generation Sequencing in Melanoma Research

Next-generation sequencing (NGS) applications have flourished in the last decade, permitting the identification of cancer driver genes and profoundly expanding the possibilities of genomic studies of cancer, including melanoma. Here we aimed to present a technical review across many of the methodological approaches brought by the use of NGS applications with a focus on assessing germline and somatic sequence variation. We provide cautionary notes and discuss key technical details involved in library preparation, the most common problems with the samples, and guidance to circumvent them. We also provide an overview of the sequence-based methods for cancer genomics, exposing the pros and cons of targeted sequencing vs. exome or whole-genome sequencing (WGS), the fundamentals of the most common commercial platforms, and a comparison of throughputs and key applications. Details of the steps and the main software involved in the bioinformatics processing of the sequencing results, from preprocessing to variant prioritization and filtering, are also provided in the context of the full spectrum of genetic variation (SNVs, indels, CNVs, structural variation, and gene fusions). Finally, we put the emphasis on selected bioinformatic pipelines behind (a) short-read WGS identification of small germline and somatic variants, (b) detection of gene fusions from transcriptomes, and (c) de novo assembly of genomes from long-read WGS data. Overall, we provide comprehensive guidance across the main methodological procedures involved in obtaining sequencing results for the most common short- and long-read NGS platforms, highlighting key applications in melanoma research

Benchmarking of human Y-chromosomal haplogroup classifiers with whole-genome and whole-exome sequence data

In anthropological, medical, and forensic studies, the nonrecombinant region of the human Y chromosome (NRY) enables accurate reconstruction of pedigree relationships and retrieval of ancestral information. Using high-throughput sequencing (HTS) data, we present a benchmarking analysis of command-line tools for NRY haplogroup classification. The evaluation was performed using paired Illumina data from whole-genome sequencing (WGS) and whole-exome sequencing (WES) experiments from 50 unrelated donors. Additionally, as a validation, we also used paired WGS/WES datasets of 54 individuals from the 1000 Genomes Project. Finally, we evaluated the tools on data from third-generation HTS obtained from a subset of donors and one reference sample. Our results show that WES, despite typically offering less genealogical resolution than WGS, is an effective method for determining the NRY haplogroup. Y-LineageTracker and Yleaf showed the highest accuracy for WGS data, classifying precisely 98% and 96% of the samples, respectively. Yleaf outperforms all benchmarked tools in the WES data, classifying approximately 90% of the samples. Yleaf, Y-LineageTracker, and pathPhynder can correctly classify most samples (88%) sequenced with third-generation HTS. As a result, Yleaf provides the best performance for applications that use WGS and WES. Overall, our study offers researchers with a guide that allows them to select the most appropriate tool to analyze the NRY region using both second- and third-generation HTS data

Digging into the admixture strata of current-day Canary Islanders based on mitogenomes

Summary: The conquest of the Canary Islands by Europeans began at the beginning of the 15th century and culminated in 1496 with the surrender of the aborigines. The collapse of the aboriginal population during the conquest and the arrival of settlers caused a drastic change in the demographic composition of the archipelago. To shed light on this historical process, we analyzed 896 mitogenomes of current inhabitants from the seven main islands. Our findings confirm the continuity of aboriginal maternal contributions and the persistence of their genetic footprints in the current population, even at higher levels (>60% on average) than previously evidenced. Moreover, the age estimates for most autochthonous founder lineages support a first aboriginal arrival to the islands at the beginning of the first millennium. We also revealed for the first time that the main recognizable genetic influences from Europe are from Portuguese and Galicians

Reinfection rate and disease severity of the BA.5 Omicron SARS-CoV-2 lineage compared to previously circulating variants of concern in the Canary Islands (Spain)

ABSTRACTThe emergence of the Omicron SARS-CoV-2 variant of concern has changed the COVID-19 scenario as this variant is characterized by high transmissibility and immune evasion ability. To evaluate the impact of this variant on the Canary Islands (Spain) population, we determined the reinfection rates and disease severity associated with the Omicron sublineages and the previously circulating variants of concern. We performed a retrospective observational study on 21,745 SARS-CoV-2 viral genomes collected from December 2020 to July 2022 in the Canary Islands (Spain). We compared the reinfection rates between lineages using pairwise proportion and Fisher’s exact tests. To assess disease severity, we studied the association of Alpha, Delta, BA.1, BA.2, BA.5, and other risk factors on 28-day hospital mortality using logistic regression and Cox proportional hazard models. We observed 127 bona fide reinfection cases throughout the study period. We found that BA.5 had the highest reinfection rate compared to other lineages (vs. Delta p = 2.89 × 10−25; vs. BA.1 p = 5.17 × 10−11; vs. BA.2 p = 0.002). Among the 1,094 hospitalized patients, multivariate logistic regression showed that Alpha (Odds Ratio [OR] =  0.45, 95% Confidence Interval [CI] =  0.23-0.87, p = 0.02), BA.2 (OR =   0.38, 95% CI = 0.22-0.63, p = 1.91 × 10−4), and BA.5 (OR = 0.30, 95% CI = 0.16-0.55, p = 1.05 × 10−4) had lower 28-day hospital mortality compared to Delta. These results were confirmed by using Cox proportional hazard models. Omicron lineages, and in particular BA.5, were associated with higher reinfection rates and lower disease severity (28-day hospital mortality) than previously circulating variants of concern

Bioinformatic approaches to draft the viral genome sequence of Canary Islands cases related to the multicountry mpox virus 2022-outbreak

On July 23, 2022, monkeypox disease (mpox) was declared a Public Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to a multicountry outbreak. In Europe, several cases of mpox virus (MPXV) infection related to this outbreak were detected in the Canary Islands (Spain). Here we describe the combination of viral DNA sequencing and bioinformatic approaches, including methods for de novo genome assembly and short- and long-read technologies, used to reconstruct the first MPXV genome isolated in the Canary Islands on the 31st of May 2022 from a male adult patient with mild symptoms. The same sequencing and bioinformatic approaches were then validated with three other positive cases of MPXV infection from the same mpox outbreak. We obtained the best results using a reference-based approach with short reads, evidencing 46–79 nucleotide variants against viral sequences from the 2018–2019 mpox outbreak and placing the viral sequences in the new B.1 sublineage of clade IIb of the MPXV classification. This study of MPXV demonstrates the potential of metagenomics sequencing for rapid and precise pathogen identification