Integrated analysis of microRNA regulation and its interaction with mechanisms of epigenetic regulation in the etiology of systemic lupus erythematosus

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p

Integrated analysis of microRNA regulation and its interaction with mechanisms of epigenetic regulation in the etiology of systemic lupus erythematosus

The aim of this study was to identity in silico the relationships among microRNAs (miRNAs) and genes encoding transcription factors, ubiquitylation, DNA methylation, and histone modifications in systemic lupus erythematosus (SLE). To identify miRNA dysregulation in SLE, we used miR2Disease and PhenomiR for information about miRNAs exhibiting differential regulation in disease and other biological processes, and HMDD for information about experimentally supported human miRNA-disease association data from genetics, epigenetics, circulating miRNAs, and miRNA-target interactions. This information was incorporated into the miRNA analysis. High-throughput sequencing revealed circulating miRNAs associated with kidney damage in patients with SLE. As the main finding of our in silico analysis of miRNAs differentially expressed in SLE and their interactions with disease-susceptibility genes, post-translational modifications, and transcription factors; we highlight 226 miRNAs associated with genes and processes. Moreover, we highlight that alterations of miRNAs such as hsa-miR-30a-5p, hsa-miR-16-5p, hsa-miR-142-5p, and hsa-miR-324-3p are most commonly associated with post-translational modifications. In addition, altered miRNAs that are most frequently associated with susceptibility-related genes are hsa-miR-16-5p, hsa-miR-374a-5p, hsa-miR-34a-5p, hsa-miR-31-5p, and hsa-miR-1-3p

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Evaluación electroquímica de recubrimientos Zn-Fe depositados con corriente pulsante

This work presents the electrochemical characterization to evaluate the corrosion resistance of Zn-Fe metal coating electroplated foil substrates cold-rolled steel. The coating is deposited by a function generator, an oscilloscope and an electrolytic cell of 50 mL, provided with a soluble anode of pure zinc. The reagents used were analytical grade, and the tests were performed at a temperature of 25oC. No complexing agents were used or polishes; so that the process is environmentally clean. The electrochemical characterization measurements made with open circuit potential, linear polarization resistance and electrochemical impedance spectroscopy show that within the range of duty cycle from 87.5% to 97.5%; and with varying frequencies between 40 Hz and 100 Hz, the effect of the reverse current pulse promotes corrosion resistance coating for frequencies of 100 Hz; the samples with higher corrosion resistance was obtained in 90% duty cycle, and are shown in the content of this article.Se presenta la caracterización electroquímica para evaluar la resistencia a la corrosión de un recubrimiento metálico Zn-Fe por vía electrolítica sobre sustratos de lámina de acero cold-rolled. Los recubrimientos se depositaron mediante un generador de funciones, un osciloscopio y una celda electrolítica de 50 ml, provista de un ánodo soluble de zinc puro. Los reactivos utilizados son de grado analítico, y las pruebas se realizaron a temperatura de 25oC. No se utilizaron agentes acomplejantes ni abrillantadores; para que el proceso sea ambientalmente limpio. La caracterización electroquímica se realizó con mediciones de potencial de circuito abierto, resistencia a la polarización lineal y Espectroscopia de Impedancia Electroquímica, los cuales muestran que dentro del rango de ciclo de trabajo desde el 87,5% al 97,5%; y con variación de frecuencias entre 40 Hz y 100 Hz, el efecto de la corriente pulsante inversa favorece la resistencia a la corrosión del recubrimiento para valores de frecuencia de 100 Hz; la muestra con mayor resistencia a la corrosión se obtuvo con un ciclo de trabajo de 90%, al tener la mayor pendiente en la curva de resistencia a la polarización lineal de las muestras analizadas

Crossed and Linked Histories of Tetrapyrrolic Macrocycles and Their Use for Engineering Pores within Sol-Gel Matrices

The crossed and linked histories of tetrapyrrolic macrocycles, interwoven with new research discoveries, suggest that Nature has found in these structures a way to ensure the continuity of life. For diverse applications porphyrins or phthalocyanines must be trapped inside solid networks, but due to their nature, these compounds cannot be introduced by thermal diffusion; the sol-gel method makes possible this insertion through a soft chemical process. The methodologies for trapping or bonding macrocycles inside pristine or organo-modified silica or inside ZrO2 xerogels were developed by using phthalocyanines and porphyrins as molecular probes. The sizes of the pores formed depend on the structure, the cation nature, and the identities and positions of peripheral substituents of the macrocycle. The interactions of the macrocyclic molecule and surface Si-OH groups inhibit the efficient displaying of the macrocycle properties and to avoid this undesirable event, strategies such as situating the macrocycle far from the pore walls or to exchange the Si-OH species by alkyl or aryl groups have been proposed. Spectroscopic properties are better preserved when long unions are established between the macrocycle and the pore walls, or when oligomeric macrocyclic species are trapped inside each pore. When macrocycles are trapped inside organo-modified silica, their properties result similar to those displayed in solution and their intensities depend on the length of the alkyl chain attached to the matrix. These results support the prospect of tuning up the pore size, surface area, and polarity inside the pore cavities in order to prepare efficient catalytic, optical, sensoring, and medical systems. The most important feature is that research would confirm again that tetrapyrrolic macrocycles can help in the development of the authentic pore engineering in materials science

Comparative Study of the Optical and Textural Properties of Tetrapyrrole Macrocycles Trapped Within ZrO2, TiO2, and SiO2 Translucent Xerogels

The entrapping of physicochemical active molecules inside mesoporous networks is an appealing field of research due to the myriad of potential applications in optics, photocatalysis, chemical sensing, and medicine. One of the most important reasons for this success is the possibility of optimizing the properties that a free active species displays in solution but now trapped inside a solid substrate. Additionally it is possible to modulate the textural characteristics of substrates, such as pore size, specific surface area, polarity and chemical affinity of the surface, toward the physical or chemical adhesion of a variety of adsorbates. In the present document, two kinds of non-silicon metal alkoxides, Zr and Ti, are employed to prepare xerogels containing entrapped tetrapyrrolic species that could be inserted beforehand in analogue silica systems. The main goal is to develop efficient methods for trapping or binding tetrapyrrole macrocycles inside TiO2 and ZrO2 xerogels, while comparing the properties of these systems against those of the SiO2 analogues. Once the optimal synthesis conditions for obtaining translucent monolithic xerogels of ZrO2 and TiO2 networks were determined, it was confirmed that these substrates allowed the entrapment, in monomeric form, of macrocycles that commonly appear as aggregates within the SiO2 network. From these experiments, it could be determined that the average pore diameters, specific surface areas, and water sorption capacities depicted by each one of these substrates, are a consequence of their own nature combined with the particular structure of the entrapped tetrapyrrole macrocycle. Furthermore, the establishment of covalent bonds between the intruding species and the pore walls leads to the obtainment of very similar pore sizes in the three different metal oxide (Ti, Zr, and Si) substrates as a consequence of the templating effect of the encapsulated species

Nadie nos quita lo baila’o. Desarrollo humano: cuerpo, escuela y convivencia

Incorporar el baile de la salsa como elemento clave de las jornadas escolares complementarias en las instituciones educativas públicas, es reconocer el valor patrimonial que tiene, pero, a su vez, validar su potencial formador o educativo si se piensa y practica pedagógicamente. Por tanto, la perspectiva de la presente cartilla considera el baile de salsa como una experiencia subjetiva y colectiva que permite promover e incorporar una serie de dimensiones del desarrollo humano que fortalezcan la formación de niños, niñas, adolescentes y jóvenes (NNAJ). Esta experiencia se configura en una mediación pedagógica en la cual los participantes se forman bailando, pero reconociendo que bailar implica conocer e incorporar en su formación tres dimensiones básicas del desarrollo humano: proyecto de vida, nutrición y hábitos de vida saludables, convivencia pacífica y resolución de conflictos.Universidad de San Buenaventura - Cal