1,210 research outputs found
Desarrollo multidisciplinario en investigaciĂłn y docencia del centro universitario UAEM Valle de MĂ©xico
DESARROLLO MULTIDISCIPLINARIO EN INVESTIGACIĂN Y DOCENCIA DEL CENTRO UNIVERSITARIO UAEM VALLE DE MĂXICOLa Universidad AutĂłnoma del Estado de MĂ©xico ha evolucionado a travĂ©s de sus 188 años de historia, dedicada a la educaciĂłn, la investigaciĂłn, la cultura y el deporte, como sus grandes ejes rectores, formadora de hombres y mujeres con un alto sentido humanista y Ă©tico, contribuyendo a lograr nuevas y mejores formas de existencia y convivencia social. Durante el proceso de desconcentraciĂłn de la UAEM, se crearon las Unidades AcadĂ©micas y Centros Universitarios para brindar el servicio de educaciĂłn a mĂĄs jĂłvenes en todo el Estado de MĂ©xico, este Centro Universitario fue uno de los primeros y a sus veinte años de existencia se estĂĄ consolidando como uno de los mejores. Es en los Ășltimos años que se ha venido impulsando la investigaciĂłn al contar con cuerpos acadĂ©micos, en formaciĂłn y en consolidaciĂłn, con infraestructura de primera tanto en equipo como en laboratorios especializados, con profesores de tiempo completo que participan en congresos, seminarios y presentan publicaciones en revistas indexadas. Por ello para celebrar esos veinte años de existencia de esta honorable instituciĂłn, se planeĂł la compilaciĂłn de esta obra que es parte del quehacer multidisciplinario en investigaciĂłn y docencia como parte del Plan de Desarrollo 2013-2017, de esta administraciĂłn. Esta obra reĂșne investigaciones tanto de profesores como de alumnos desde las diferentes ramas del saber en las que se inscriben sus siete licenciaturas, ActuarĂa, AdministraciĂłn, ContadurĂa, Derecho, EconomĂa, Relaciones EconĂłmicas Internacionales e InformĂĄtica Administrativa, tanto presencial como a distancia, asĂ como sus tres ingenierĂas, Industrial, en ComputaciĂłn y Sistemas y Comunicaciones, asĂ como gracias a la vinculaciĂłn y colaboraciĂłn acadĂ©mico â cientĂfica que se tiene con otras instituciones de educaciĂłn superior a nivel nacional, como el Instituto TecnolĂłgico de Orizaba, la Universidad AutĂłnoma de San Luis PotosĂ, la Universidad Nacional AutĂłnoma de MĂ©xico, la Universidad AutĂłnoma Metropolitana, Universidad PolitĂ©cnica de Victoria, el Instituto PolitĂ©cnico Nacional entre otras. En el capĂtulo 1 se abordan seis temĂĄticas diferentes de vanguardia en el ĂĄrea de las IngenierĂas, en los capĂtulos 2 y 3 se incluyen temas de interĂ©s y gran relevancia en materia de ciencias sociales, polĂtica y economĂa. Se hace extensivo un reconocimiento para todos los que participaron tanto en la revisiĂłn de los trabajos, como en la compilaciĂłn del producto final de este Libro intitulado âDesarrollo Multidisciplinario en InvestigaciĂłn y Docencia del Centro Universitario UAEM Valle de MĂ©xicoâ
Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals
The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.Funding: Research reported in this publication was supported in part by the National Cancer Institute of the NIH (5R01HD102614-02; R01CA249204 and R01CA248984) and an ISMMS seed fund to E.G. The authors gratefully acknowledge use of the services and facilities of the Tisch Cancer Institute supported by a NCI Cancer Center Support Grant (P30 CA196521). M.S. was supported by a NCI training grant (T32CA078207). This work was supported by an ISMMS seed fund to J.O.; Instituto de Salud Carlos III (COV20-00668) to R.C.R.; the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181) co-financed by the European Development Regional Fund ââA way to achieve Europeââ to E.P.; the Instituto de Salud Carlos III, Spain (COV20/00170); the Government of Cantabria, Spain (2020UIC22-PUB-0019) to M.L.H.; the Instituto de Salud Carlos III (PI16CIII/00012) to P.P.; the Fondo Social Europeo e Iniciativa de Empleo Juvenil YEI (Grant PEJ2018-004557-A) to M.P.E.; and by REDInREN 016/009/009 ISCIII. This project has received funding from the European Union Horizon 2020 research and innovation programs VACCELERATE and INsTRuCT under grant agreements 101037867 and 860003
Differential effects of the second SARS-CoV-2 mRNA vaccine dose on TÂ cell immunity in naive and COVID-19 recovered individuals
The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in detail. In this study, we characterize SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during and after two doses of BNT162b2 vaccination. Our results demonstrate that, while the second dose increases both the humoral and cellular immunity in naive individuals, COVID-19 recovered individuals reach their peak of immunity after the first dose. These results suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.Research reported in this publication was supported in part by the National Cancer Institute of the NIH (5R01HD102614-02; R01CA249204 and R01CA248984) and an ISMMS seed fund to E.G. The authors gratefully acknowledge use of the services and facilities of the Tisch Cancer Institute supported by a NCI Cancer Center Support Grant (P30 CA196521). M.S. was supported by a NCI training grant (T32CA078207). This work was supported by an ISMMS seed fund to J.O.; Instituto de Salud Carlos III (COV20-00668) to R.C.R.; the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 research call COV20/00181) co-financed by the European Development Regional Fund âA way to achieve Europeâ to E.P.; the Instituto de Salud Carlos III, Spain (COV20/00170); the Government of Cantabria, Spain (2020UIC22-PUB-0019) to M.L.H.; the Instituto de Salud Carlos III (PI16CIII/00012) to P.P.; the Fondo Social Europeo e Iniciativa de Empleo Juvenil YEI (Grant PEJ2018-004557-A) to M.P.E.; and by REDInREN 016/009/009 ISCIII. This project has received funding from the European Union Horizon 2020 research and innovation programs VACCELERATE and INsTRuCT under grant agreements 101037867 and 860003.S
Activating Transcription Factor 4 Modulates TGFÎČ-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling
Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFÎČ1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFÎČ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFÎČ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFÎČ was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFÎČ/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer
Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort
Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD
Contribución de la producción animal en pequeña escala al desarrollo rural
La producciĂłn y el consumo de productos de origen animal han experimentado un rĂĄpido crecimiento en todo el mundo, y se prevĂ© que continuarĂĄn aumentando. Se considera que la mayor parte del incremento en la producciĂłn provendrĂĄ de sistemas de producciĂłn en pequeña escala, que representan el medio de vida de hasta un 70% de la poblaciĂłn rural pobre del mundo.1 La producciĂłn animal en pequeña escala se reconoce en todo el mundo como un elemento que contribuye al alivio de la pobreza en el medio rural, mediante generaciĂłn de ingresos, oportunidades de ocupaciĂłn y dinamismo del uso de los recursos disponibles. Por lo tanto, es de suma importancia conocer las dinĂĄmicas de estos sistemas de producciĂłn animal y su contribuciĂłn al desarrollo rural en MĂ©xico. Investigadores y extensionistas deben priorizar las demandas de la producciĂłn animal en las comunidades rurales, ya que la producciĂłn animal en pequeña escala ha contribuido a mejorar la calidad de vida y a disminuir la vulnerabilidad de las familias productoras. En el MĂ©xico prehispĂĄnico la poblaciĂłn sĂłlo criaba xoloitzcuintle y guajolotes como animales domĂ©sticos, y complementaba en proteĂnas su dieta con la caza y la pesca. Sin embargo, con la llegada de los españoles en 1521 llegaron tambiĂ©n los primeros bovinos a la Nueva España, que se reprodujeron con suma rapidez. La carne de bovino llegĂł a constituir una parte sustancial de la dieta alimenticia de toda la poblaciĂłn.2 A pesar de que al inicio la producciĂłn animal era casi nula, Ă©sta empezĂł a desarrollarse rĂĄpidamente y en la actualidad representa un pilar importante para el desarrollo rural en las familias campesinas de nuestro paĂs, pues es vista como una fuente de ingreso
CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative
Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodiumâglucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with reninâangiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years
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 Δ4 allele
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