Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Species and population specific gene expression in blood transcriptomes of marine turtles.

BACKGROUND: Transcriptomic data has demonstrated utility to advance the study of physiological diversity and organisms' responses to environmental stressors. However, a lack of genomic resources and challenges associated with collecting high-quality RNA can limit its application for many wild populations. Minimally invasive blood sampling combined with de novo transcriptomic approaches has great potential to alleviate these barriers. Here, we advance these goals for marine turtles by generating high quality de novo blood transcriptome assemblies to characterize functional diversity and compare global transcriptional profiles between tissues, species, and foraging aggregations. RESULTS: We generated high quality blood transcriptome assemblies for hawksbill (Eretmochelys imbricata), loggerhead (Caretta caretta), green (Chelonia mydas), and leatherback (Dermochelys coriacea) turtles. The functional diversity in assembled blood transcriptomes was comparable to those from more traditionally sampled tissues. A total of 31.3% of orthogroups identified were present in all four species, representing a core set of conserved genes expressed in blood and shared across marine turtle species. We observed strong species-specific expression of these genes, as well as distinct transcriptomic profiles between green turtle foraging aggregations that inhabit areas of greater or lesser anthropogenic disturbance. CONCLUSIONS: Obtaining global gene expression data through non-lethal, minimally invasive sampling can greatly expand the applications of RNA-sequencing in protected long-lived species such as marine turtles. The distinct differences in gene expression signatures between species and foraging aggregations provide insight into the functional genomics underlying the diversity in this ancient vertebrate lineage. The transcriptomic resources generated here can be used in further studies examining the evolutionary ecology and anthropogenic impacts on marine turtles.

Elevated Heterozygosity in Adults Relative to Juveniles Provides Evidence of Viability Selection on Eagles and Falcons.

Viability selection yields adult populations that are more genetically variable than those of juveniles, producing a positive correlation between heterozygosity and survival. Viability selection could be the result of decreased heterozygosity across many loci in inbred individuals and a subsequent decrease in survivorship resulting from the expression of the deleterious alleles. Alternatively, locus-specific differences in genetic variability between adults and juveniles may be driven by forms of balancing selection, including heterozygote advantage, frequency-dependent selection, or selection across temporal and spatial scales. We use a pooled-sequencing approach to compare genome-wide and locus-specific genetic variability between 74 golden eagle (Aquila chrysaetos), 62 imperial eagle (Aquila heliaca), and 69 prairie falcon (Falco mexicanus) juveniles and adults. Although genome-wide genetic variability is comparable between juvenile and adult golden eagles and prairie falcons, imperial eagle adults are significantly more heterozygous than juveniles. This evidence of viability selection may stem from a relatively smaller imperial eagle effective population size and potentially greater genetic load. We additionally identify ~2000 single-nucleotide polymorphisms across the 3 species with extreme differences in heterozygosity between juveniles and adults. Many of these markers are associated with genes implicated in immune function or olfaction. These loci represent potential targets for studies of how heterozygote advantage, frequency-dependent selection, and selection over spatial and temporal scales influence survivorship in avian species. Overall, our genome-wide data extend previous studies that used allozyme or microsatellite markers and indicate that viability selection may be a more common evolutionary phenomenon than often appreciated.

Doble ruptura miocárdica como complicación mecánica de un infarto agudo / Double myocardial rupture as a mechanical complication of an acute infarction

Resumen Las complicaciones del infarto agudo de miocardio se clasifican en mecánicas, eléctricas, isquémicas, tromboembólicas e inflamatorias; entre las complicaciones mecánicas destaca la ruptura de la pared libre del ventrículo izquierdo, músculos papilares y del septum ventricular, con incidencia menor de 1%, que ha descendido con la introducción de la intervención coronaria percutánea como principal estrategia de reperfusión. Se comunica el caso de una paciente de 64 años de edad, que acudió a urgencias por un cuadro de dolor torácico agudo compatible con síndrome coronario agudo con elevación del segmento ST (SICACEST) y durante su evolución tuvo deterioro clínico, se identificó una doble ruptura miocárdica. Se plantea el abordaje del caso y se revisa la bibliografía, porque una doble ruptura miocárdica corresponde solo a 0.3% de los casos reportados.

Abstract The complications of acute myocardial infarction are classified in mechanical, electrical, ischemic, embolic and inflammatory. The main mechanical complications are free wall rupture, papillary muscle and ventricular septal rupture. Its incidence is less than 1% and has decreased with the introduction of percutaneous coronary intervention as the main reperfusion strategy. This article presents a clinical case of a 64-year-old female that arrived to emergency room with thoracic pain, due to an acute coronary syndrome: ST-elevation myocardial infarction (STEMI); with a clinical deterioration presenting a double myocardial rupture. Clinical approach and bibliographic review are reported, the incidence estimation of this disorder is only 0.3% of the reported clinical cases.

Efecto cardiometabólico de los inhibidores del cotransportador sodio glucosa tipo 2 (SGLT2) / Cardiometabolic effect of inhibitors of sodium glucose cotransporter type 2 (SGLT2)

Resumen: El advenimiento de nuevos fármacos para el tratamiento de los distintos componentes del síndrome metabólico, que por su farmacocinética y farmacodinamia tengan un efecto pleiotrópico, ha tomado auge. Hace poco los inhibidores del cotransportador sodio glucosa tipo 2 (SGLT2) prescritos para el tratamiento de la diabetes mellitus 2 han demostrado tener un efecto protector cardiorrenal. Éstos actúan en el segmento S1 del túbulo proximal disminuyendo la filtración de glucosa e incrementando su excreción urinaria; con efecto glucosúrico y natriurético. Este último es el principal mecanismo de protección cardiovascular. Modelos experimentales y estudios, entre los que destacan el estudio EMPAREG y el programa CANVAS, han demostrado que los inhibidores de SGLT2 permiten disminuir la progresión de la miocardiopatía hipertrófica, fibrosis, remodelamiento, disfunción sistólica e insuficiencia cardiaca, por su efecto en la precarga y poscarga. Los resultados de estos estudios reconocen a este grupo de fármacos (específicamente a la empagliflozina y canagliflozina) como tratamiento de protección cardiovascular en pacientes con diabetes mellitus 2, recomendados actualmente por la FDA, ACC/AHA, la Sociedad Europea de Cardiología y recientemente por la Asociación Americana de Diabetes (ADA) en su reciente publicación de 2018.

Abstract: There is an increase in the use of new drugs for the treatment of the different elements that integrate the metabolic syndrome; that, by their pharmacokinetics and pharmacodynamics have a pleiotropic effect. Recently, the inhibitors of sodium glucose cotransporter type 2 (SGLT2) used for the treatment of diabetes mellitus type 2 have demonstrated a cardio-renal protector effect. They function at the S1 segment of the proximal tube, lowering the filtration of glucose and enhancing its excretion; resulting in a glycosuric and natriuretic effect. This is the main mechanism of cardiovascular protection. Experimental essays and different studies, such as the EMAREG study and the CANVAS program, have established that the inhibitors of SGLT2 reduce the progression of hypertrophic cardiomyopathy, fibrosis, cardiac remodeling, systolic dysfunction and heart failure. The results of these studies recognize this group of drugs (empaglifozine and canaglifozine) as a valid treatment for cardiovascular protection in patients with diabetes mellitus type 2, and which is recommended by the FDA, the ACC/AHA, the European Society of Cardiology and the American Diabetes Association (ADA) in its last publication in 2018.

Characterization of the Gray Whale Eschrichtius robustus Genome and a Genotyping Array Based on Single-Nucleotide Polymorphisms in Candidate Genes.

Genetic and genomic approaches have much to offer in terms of ecology, evolution, and conservation. To better understand the biology of the gray whale Eschrichtius robustus (Lilljeborg, 1861), we sequenced the genome and produced an assembly that contains ∼95% of the genes known to be highly conserved among eukaryotes. From this assembly, we annotated 22,711 genes and identified 2,057,254 single-nucleotide polymorphisms (SNPs). Using this assembly, we generated a curated list of candidate genes potentially subject to strong natural selection, including genes associated with osmoregulation, oxygen binding and delivery, and other aspects of marine life. From these candidate genes, we queried 92 autosomal protein-coding markers with a panel of 96 SNPs that also included 2 sexing and 2 mitochondrial markers. Genotyping error rates, calculated across loci and across 69 intentional replicate samples, were low (0.021%), and observed heterozygosity was 0.33 averaged over all autosomal markers. This level of variability provides substantial discriminatory power across loci (mean probability of identity of 1.6 × 10-25 and mean probability of exclusion >0.999 with neither parent known), indicating that these markers provide a powerful means to assess parentage and relatedness in gray whales. We found 29 unique multilocus genotypes represented among our 36 biopsies (indicating that we inadvertently sampled 7 whales twice). In total, we compiled an individual data set of 28 western gray whales (WGSs) and 1 presumptive eastern gray whale (EGW). The lone EGW we sampled was no more or less related to the WGWs than expected by chance alone. The gray whale genomes reported here will enable comparative studies of natural selection in cetaceans, and the SNP markers should be highly informative for future studies of gray whale evolution, population structure, demography, and relatedness.

Golden Eagle fatalities and the continental-scale consequences of local wind-energy generation.

Renewable energy production is expanding rapidly despite mostly unknown environmental effects on wildlife and habitats. We used genetic and stable isotope data collected from Golden Eagles (Aquila chrysaetos) killed at the Altamont Pass Wind Resource Area (APWRA) in California in demographic models to test hypotheses about the geographic extent and demographic consequences of fatalities caused by renewable energy facilities. Geospatial analyses of δ2 H values obtained from feathers showed that ≥25% of these APWRA-killed eagles were recent immigrants to the population, most from long distances away (>100 km). Data from nuclear genes indicated this subset of immigrant eagles was genetically similar to birds identified as locals from the δ2 H data. Demographic models implied that in the face of this mortality, the apparent stability of the local Golden Eagle population was maintained by continental-scale immigration. These analyses demonstrate that ecosystem management decisions concerning the effects of local-scale renewable energy can have continental-scale consequences.

The impacts of inbreeding, drift and selection on genetic diversity in captive breeding populations.

The goal of captive breeding programmes is often to maintain genetic diversity until re-introductions can occur. However, due in part to changes that occur in captive populations, approximately one-third of re-introductions fail. We evaluated genetic changes in captive populations using microsatellites and mtDNA. We analysed six populations of white-footed mice that were propagated for 20 generations using two replicates of three protocols: random mating (RAN), minimizing mean kinship (MK) and selection for docility (DOC). We found that MK resulted in the slowest loss of microsatellite genetic diversity compared to RAN and DOC. However, the loss of mtDNA haplotypes was not consistent among replicate lines. We compared our empirical data to simulated data and found no evidence of selection. Our results suggest that although the effects of drift may not be fully mitigated, MK reduces the loss of alleles due to inbreeding more effectively than random mating or docility selection. Therefore, MK should be preferred for captive breeding. Furthermore, our simulations show that incorporating microsatellite data into the MK framework reduced the magnitude of drift, which may have applications in long-term or extremely genetically depauperate captive populations.

Mitochondria, Energy and Cancer: The Relationship with Ascorbic Acid.

Ascorbic Acid (AA) has been used in the prevention and treatment of cancer with reported effectiveness. Mitochondria may be one of the principal targets of ascorbate's cellular activity and it may play an important role in the development and progression of cancer. Mitochondria, besides generating adenosine triphosphate (ATP), has a role in apoptosis regulation and in the production of regulatory oxidative species that may be relevant in gene expression. At higher concentrations AA may increase ATP production by increasing mitochondrial electron flux, also may induce apoptotic cell death in tumor cell lines, probably via its pro-oxidant action In contrast, at lower concentrations AA displays antioxidant properties that may prevent the activation of oxidant-induced apoptosis. These concentration dependent activities of ascorbate may explain in part the seemingly contradictory results that have been reported previously.

Grasa parda / Postgraduate medical specialties

La obesidad ha alcanzado proporciones epidèmicas, las complicaciones relacionadas con ella contribuyen sustancialmente al costo de salud.