Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Comparison of DNA quantity and quality from fecal samples of mammals transported in ethanol or lysis buffer.

Using fecal microbial community profiles through sequencing approaches helps to unravel the intimate interplay between health, wellness, and diet in wild animals with their environment. Ensuring the proper preservation of fecal samples before processing is crucial to ensure reliable results. In this study, we evaluated the efficiency of two different preservation methods, considering the following criteria: DNA yield, quality and integrity, and microbial community structure based on Oxford Nanopore amplicon sequencing of the V3-V4 region of bacterial 16S rRNA and protozoa 18S rRNA genes. Eighteen matched pairs of mammalian fecal samples were collected and transported in 99.8% ethanol and lysis buffer; processing occurred between 55 and 461 days post-collection. Wilcoxon signed-rank tests were used to analyze quantitative measurements for paired samples. The A260/280 ratio, a measure of nucleic acid purity, was assessed descriptively for each media, and the Bartlett test evaluated dispersion of this ratio. A Fisher test was performed to compare the number of positive reactions for DNA extraction or PCR amplification of the 16S and 18S rRNA genes between both media. The concentration of total DNA and amplicons, as well as the number of reads obtained in sequencing, was significantly higher in the samples preserved with lysis buffer compared to ethanol, with magnitudes up to three times higher. Electrophoretic analysis of total DNA and amplicons further confirmed superior DNA integrity in lysis buffer preserved samples. The A260/280 values  obtained using the lysis buffer were of optimal purity (mean: 1.92) and with little dispersion (SD: 0.27); on the other hand, the ethanol samples also presented an excellent average quality (mean: 1.94), but they were dispersed (SD: 1.10). For molecular studies using mammalian feces, the lysis buffer reagent proved to be a reliable solution for their collection, conservation, and storage.

Soil bacteria and fungi communities are shaped by elevation influences in Colombian forest and páramo natural ecosystems

The influence of elevation on natural terrestrial ecosystems determines the arrangements of microbial communities in soils to be associated with biotic and abiotic factors. To evaluate changes of fungi and bacteria at the community level along an elevational gradient (between 1000 and 3800 m.a.s.l.), physicochemical measurements of soils, taxonomic identifications of plants, and metabarcoding sequences of the 16S rRNA gene for bacteria and the ITS1 region for fungi were obtained. The bacterial taxonomic composition showed that Acidobacteriota increased in abundance with elevation, while Actinobacteriota and Verrucomicrobiota decreased. Furthermore, Firmicutes and Proteobacteria maintained maximum levels of abundance at intermediate elevations (1200 and 2400 m.a.s.l.). In fungi, Ascomycota was more abundant at higher elevations, Basidiomycota tended to dominate at lower elevations, and Mortierellomycota had a greater presence at intermediate sites. These results correlated with the edaphic parameters of decreasing pH and increasing organic carbon and available nitrogen with elevation. In addition, the Shannon index found a greater diversity in bacteria than fungi, but both showed a unimodal pattern with maximum values in the Andean Forest at 2400 m.a.s.l. Through the microbial characterization of the ecosystems, the elevational gradient, soil properties, and vegetation were found to exert significant effects on microbial communities and alpha diversity indices. We conclude that the most abundant soil microorganisms at the sampling points differed in abundance and diversity according to the variations in factors influencing ecological communities. (AU)

Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study.

BACKGROUND: Up to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients. METHODS: This was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality. RESULTS: The 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07-3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47-4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018). CONCLUSIONS: High age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Exploring Genomics and Microbial Ecology: Analysis of Bidens pilosa L. Genetic Structure and Soil Microbiome Diversity by RAD-Seq and Metabarcoding.

Bidens pilosa L., native to South America and commonly used for medicinal purposes, has been understudied at molecular and genomic levels and in its relationship with soil microorganisms. In this study, restriction site-associated DNA markers (RADseq) techniques were implemented to analyze genetic diversity and population structure, and metabarcoding to examine microbial composition in soils from Palmira, Sibundoy, and Bogotá, Colombia. A total of 2,984,123 loci and 3485 single nucleotide polymorphisms (SNPs) were identified, revealing a genetic variation of 12% between populations and 88% within individuals, and distributing the population into three main genetic groups, FST = 0.115 (p < 0.001) and FIT = 0.013 (p > 0.05). In the soil analysis, significant correlations were found between effective cation exchange capacity (ECEC) and apparent density, soil texture, and levels of Mg and Fe, as well as negative correlations between ECEC and Mg, and Mg, Fe, and Ca. Proteobacteria and Ascomycota emerged as the predominant bacterial and fungal phyla, respectively. Analyses of alpha, beta, and multifactorial diversity highlight the influence of ecological and environmental factors on these microbial communities, revealing specific patterns of clustering and association between bacteria and fungi in the studied locations.

Supervivencia de pacientes con síndrome de bajo gasto cardiaco en el periodo posoperatorio / Survival of patients with low cardiac output syndrome in the postoperative period i: en

Introducción: La intervención quirúrgica cardiaca es compleja, pero con resultados satisfactorios para el paciente, pues incrementa su supervivencia y calidad de vida. El síndrome de bajo gasto cardiaco en el periodo posoperatorio es una de las entidades que ensombrece el pronóstico y eleva los índices de morbilidad y mortalidad en dichos pacientes. Objetivo: Estimar la supervivencia de los pacientes con síndrome de bajo gasto cardiaco en el periodo posoperatorio según variables clínicas y ecocardiográficas. Métodos: Se realizó una investigación de cohorte de supervivencia en 56 pacientes operados del corazón, diagnosticados con síndrome de bajo gasto cardiaco posoperatorio, quienes fueron atendidos en el Centro de Cardiología y Cirugía Cardiovascular de Santiago de Cuba, desde enero del 2019 hasta noviembre del 2021. Resultados: Predominaron el grupo etario de 65 o más años (60,7 %), la diabetes mellitus (44,6 %) como antecedente patológico personal y los pacientes con fracción de eyección de 45 % o más, quienes presentaron mayor cantidad de decesos (29,8 %). La función del ventrículo derecho afectada se halló en 52,6 % de los fallecidos. El tiempo de circulación extracorpórea de 90 minutos o más primó en 67,9 % de los afectados, de los cuales 42,1 % murieron. Conclusiones: Se observó que la diabetes mellitus, el tiempo de circulación extracorpórea y el sangrado perioperatorio prolongados, así como la función sistólica biventricular se relacionaron con el pronóstico del síndrome de bajo gasto cardiaco en el periodo posoperatorio.

Introduction: Heart surgical intervention is complex, but with satisfactory results for the patient, because it increases his survival and life quality. The low cardiac output syndrome in the postoperative period is one of the entities that darkens the prognosis of this operation and elevates the morbidity and mortality indexes in these patients. Objective: To estimate the survival of patients with low cardiac output syndrome in the postoperative period according to clinical and echocardiographyc variables. Methods: A cohort investigation of survival in 56 operated patients was carried out, who were diagnosed with postoperative low cardiac output syndrome and were assisted in the Cardiology and Cardiovascular Surgery Center of Santiago de Cuba, from January, 2019 to November, 2021. Results: There was prevalence of the 65 years and over age group (60.7%), the diabetes mellitus (44.6%) as personal pathological history and patients with ejection fraction of 45% or more who presented higher quantity of deaths (29.8%). The function of the affected right ventricle was found in 52.6% of deaths. The time of extracorporeal circulation of 90 minutes or more prevailed in 67.9% of those affected, of whom 42.1% died. Conclusions: It was observed that diabetes mellitus, the time of extracorporeal circulation and the long perioperative bleeding, as well as the biventricular systolic function was related to the prognosis of low cardiac output syndrome in the postoperative period.

Ethnobotanical Insights: Qualitative Analysis of Medicinal Plants in Colón Putumayo for Traditional Knowledge Preservation.

The ancestral knowledge of the community of Colón Putumayo unfolds in several dimensions that allow us to recognise the ethnomedicinal properties of plants. The research focused on systematising ethnobotanical and ethnomedicinal knowledge on the use of plants as alternatives for treating illnesses. A cross-sectional study was carried out through semi-structured questionnaires to 100 inhabitants of the community of Colón. We found 38 plant species catalogued in 18 botanical families where 10 species of medicinal plants were prioritised by the community for the treatment of illnesses. The use value (UV) evaluation showed that Chamaemelum nobile equals 0.18 compared to Cymbopogon citratus and Lippia alba with 0.04. The Informant Consensus Factor (ICF) for the cited medicinal use categories equivalent to 1.00 are for the treatment of six types of ailments, however, the plants can treat 16 types of ailments. The Fidelity Level (LF) found identified that four plants are used for the treatment of one type of ailment while three are used to alleviate several ailments. The local knowledge of the community of Colón Putumayo is linked to the ancestry of the territory, culture, and family farming practices.

Genome-wide association study reveals candidate genes for traits related to meat quality in Colombian Creole hair sheep.

Genome-wide association studies (GWAS) allow identifying genomic regions related to traits of economic importance in animals of zootechnical interest. The objective of this research was to conduct a genome-wide association study on meat quality traits using the Illumina OvineSNPs50 BeadChip array. The animals were sampled in the departments of Córdoba, Cesar, and Valle del Cauca. The genotypes obtained with the Illumina OvineSNP50 BeadChip microarray were analyzed SNP (single-nucleotide polymorphism) data to conduct a GWAS for pH and water-holding capacity (WHC) traits measured after 7 days of maturation, in the Longissimus dorsi (LD) muscle, in 167 Creole hair sheep of 12 months old belonging to Pelibuey (CHSP, n = 60), Ethiopian (CHSE, n = 44), and Sudan (CHSS, n = 63) breeds. The GWAS was done using a mixed linear model (MLMA) and based on the Ovis aries v3.1 genome. The CHSE showed the lowest meat juice release and, consequently, the highest water-holding capacity (WHC = 30.6 ± 0.1), suggesting that this breed has better performance in the meat industry compared with CHSS (WHC = 41.7 ± 0.1) and CHSP (WHC = 36.8 ± 0.1), since there is a relationship between WHC and juiciness. For the character pH, it was not possible to annotate genes related to meat quality, while, for the WHC, they have obtained 11 candidate genes associated (ELOVL2, ARAP2, LOC101102527, SHOC2, AIPL1, CSRNP3, IFRD, KDM8, NANS, DAPK1, IBN2, TPM2). Particularly, ELOVL2, ARAP2, IBN2, and TPM2 genes are involved in muscle contraction and fatty acid composition in sheep. In this study, we generated a baseline for GWAS related to meat quality traits in Colombian Creole hair sheep that can be used for future genomic selection plans.

Regulación de la respuesta inflamatoria dependiente de citocinas / Regulation of the inflammatory response dependent on cytokines i: en

Las citocinas son hormonas proteicas que permiten la comunicación intercelular, estimulan la activación de receptores de membrana específicos, poseen funciones de diferenciación celular y proliferación, participan en la quimiotaxis, así como en el crecimiento y la modulación de la secreción de inmunoglobulinas; no obstante, su acción principal está dada por la regulación del mecanismo de la inflamación. Las principales citocinas encargadas de esto son las interleucinas 1, 8, 12 y 16; además del factor de necrosis tumoral alfa e interferones, todas ellas proinflamatorias. Las interleucinas 6 y 12 también actúan en la inmunidad específica.

Cytokines are protein hormones that allow the intercellular communication, stimulate the activation of specific membrane receptors, have cell differentiation functions and proliferation, participate in the chemotaxis, as well as in the growth and modulation of immunoglobulin secretion; nevertheless, their main action is given by the regulation of the inflammation mechanism. The main cytokines in charge of this are interleukins 1, 8, 12 and 16, besides the tumor necrosis factor alpha and interferons, all of them proinflammatory. Interleukins 6 and 12 also act in the specific immunity.

Active cancer as the main predictor of mortality for COVID-19 in oncology patients in a specialized center.

Introduction: The role of the type, stage and status of cancer in the outcome of COVID-19 remains unclear. Moreover, the characteristic pathological changes of severe COVID-19 reveled by laboratory and radiological findings are similar to those due to the development of cancer itself and antineoplastic therapies. Objective: To identify potential predictors of mortality of COVID-19 in cancer patients. Materials and methods: A retrospective and cross-sectional study was carried out in patients with clinical suspicion of COVID-19 who were confirmed for COVID-19 diagnosis by RT-PCR testing at the National Institute of Neoplastic Diseases between April and December 2020. Demographic, clinical, laboratory and radiological data were analyzed. Statistical analyses included area under the curve and univariate and multivariate logistic regression analyses. Results: A total of 226 patients had clinical suspicion of COVID-19, the diagnosis was confirmed in 177 (78.3%), and 70/177 (39.5%) died. Age, active cancer, leukocyte count ≥12.8 × 109/L, urea ≥7.4 mmol/L, ferritin ≥1,640, lactate ≥2.0 mmol/L, and lung involvement ≥35% were found to be independent predictors of COVID-19 mortality. Conclusion: Active cancer represents the main prognosis factor of death, while the role of cancer stage and type is unclear. Chest CT is a useful tool in the prognosis of death from COVID-19 in cancer patients. It is a challenge to establish the prognostic utility of laboratory markers as their altered values it could have either oncological or pandemic origins.

Phytochemical Profile and Composition of Chickpea (Cicer arietinum L.): Varietal Differences and Effect of Germination under Elicited Conditions.

Germination is a simple process that improves the nutritional and medicinal values of seeds such as chickpeas. However, the detailed analysis of the phytochemical profile after chemical elicitation during chickpea germination is indispensable when making inferences about its biological properties. Therefore, an evaluation was made of the effect of the chemical inducers salicylic acid (SA, 1 and 2 mM), chitosan (CH, 3.3 and 7 µM), and hydrogen peroxide (H2O2, 20 and 30 mM) during germination at 25 °C with 70% RH for 4 days on the content of antinutritional and bioactive compounds, including phenolics, sterols, and saponins, in three Mexican chickpea varieties (Blanoro, Patron, and San Antonio) using UPLC-ELSD-ESI-QqQ-MS/MS, UPLC-DAD-ESI-QqQ-MS/MS, and HPLC-DAD-sQ-MS. The highest increase in phenolics and saponins was found in the Blanoro sprouts induced with SA 2 mM, whereas the highest phytosterol content was detected in San Antonio sprouts induced with CH 7 µM. In addition, significant increases in mono-, di-, and oligosaccharides and decreases in antinutritional contents were achieved after germination with most of the elicitation conditions. More importantly, we identified new compounds in chickpea sprouts, such as the lignans matairesinol and secoisolariciresinol, the phenolic compounds epicatechin gallate and methyl gallate, some phytosterols, and the saponin phaseoside 1, which further increased after chemical elicitation.

Soil bacteria and fungi communities are shaped by elevation influences in Colombian forest and páramo natural ecosystems.

The influence of elevation on natural terrestrial ecosystems determines the arrangements of microbial communities in soils to be associated with biotic and abiotic factors. To evaluate changes of fungi and bacteria at the community level along an elevational gradient (between 1000 and 3800 m.a.s.l.), physicochemical measurements of soils, taxonomic identifications of plants, and metabarcoding sequences of the 16S rRNA gene for bacteria and the ITS1 region for fungi were obtained. The bacterial taxonomic composition showed that Acidobacteriota increased in abundance with elevation, while Actinobacteriota and Verrucomicrobiota decreased. Furthermore, Firmicutes and Proteobacteria maintained maximum levels of abundance at intermediate elevations (1200 and 2400 m.a.s.l.). In fungi, Ascomycota was more abundant at higher elevations, Basidiomycota tended to dominate at lower elevations, and Mortierellomycota had a greater presence at intermediate sites. These results correlated with the edaphic parameters of decreasing pH and increasing organic carbon and available nitrogen with elevation. In addition, the Shannon index found a greater diversity in bacteria than fungi, but both showed a unimodal pattern with maximum values in the Andean Forest at 2400 m.a.s.l. Through the microbial characterization of the ecosystems, the elevational gradient, soil properties, and vegetation were found to exert significant effects on microbial communities and alpha diversity indices. We conclude that the most abundant soil microorganisms at the sampling points differed in abundance and diversity according to the variations in factors influencing ecological communities.

A review of the global emergence of multidrug-resistant Salmonella enterica subsp. enterica Serovar Infantis.

Salmonella enterica serovar Infantis is an emergent foodborne and zoonotic Salmonella serovar with critical implications for global health. In recent years, the prevalence of S. Infantis infections has increased in the United States, Europe, and Latin America, due to contaminated chicken and other foods. An essential trait of S. Infantis is its resistance to multiple antibiotics, including the critically important third-generation cephalosporins and quinolones, undermining effective medical treatment, particularly in low-resource settings. We describe the emergence of multidrug-resistant (MDR) S. Infantis, focusing on humans, animals, the environment, and food. We conducted a systematic review (1979-2021), selected 183 studies, and analyzed the origin, source, antimicrobial resistance, and presence of a conjugative plasmid of emerging S. Infantis (pESI) in reported isolates. S. Infantis has been detected worldwide, with a substantial increase since 2011. We found the highest number of isolations in the Americas (42.9 %), Europe (29.8 %), Western Pacific (17.2 %), Eastern Mediterranean (6.6 %), Africa (3.4 %), and South-East Asia (0.1 %). S. Infantis showed MDR patterns and numerous resistant genes in all sources. The primary source of MDR S. Infantis is broiler and their meat; however, this emerging pathogen is also present in other reservoirs such as food, wildlife, and the environment. Clinical cases of MDR S. Infantis have been reported in children and adults. The global emergence of S. Infantis is related to a plasmid (pESI) with antibiotic and arsenic- and mercury-resistance genes. Additionally, a new megaplasmid (pESI-like), carrying blaCTX-M-65 and antibiotic-resistant genes reported in an ancestral version, was detected in the broiler, human, and chicken meat isolates. Strains harboring pESI-like were primarily observed in the Americas and Europe. MDR S. Infantis has spread globally, potentially becoming a major public health threat, particularly in low- and middle-income countries.

Soil Bacterial Communities from Three Agricultural Production Systems in Rural Landscapes of Palmira, Colombia.

Soils play important roles in the proper functioning of agroecosystems. Using molecular characterization methods such as metabarcoding, soils from eight farms (57 samples) belonging to three production system types-agroecological (two farms with twenty-two sampling points), organic (three farms with twenty-one sampling points), and conventional (three farms with fourteen sampling points)-were compared from the rural villages of El Arenillo and El Mesón in Palmira, Colombia. Amplification and sequencing of the hypervariable V4 region of the 16S rRNA gene was performed using next-generation sequencing (Illumina MiSeq) to estimate the bacterial composition and the alpha and beta diversity present. Across all soil samples, we found 2 domains (Archaea and Bacteria), 56 phylum, 190 classes, 386 orders, 632 families, and 1101 genera to be present. The most abundant phyla in the three systems were Proteobacteria, (agroecological 28%, organic 30%, and conventional 27%), Acidobacteria (agroecological 22%, organic 21%, and conventional 24%), and Verrucomicrobia (agroecological 10%, organic 6%, and conventional 13%). We found 41 nitrogen-fixing and phosphate-dissolving genera which promote growth and pathogens. Alpha and beta diversity indices were very similar across the three agricultural production systems, as reflected by shared amplicon sequence variants (ASVs) among them, likely due to the proximity of the sampling sites and recent management changes.

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year.

Background and objective: Prolonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up. Methods: We conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed. Results: Thirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year. Conclusions: Prolonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis.

Structure-function relationships in the sodium chloride cotransporter.

The thiazide sensitive Na+:Cl- cotransporter (NCC) is the principal via for salt reabsorption in the apical membrane of the distal convoluted tubule (DCT) in mammals and plays a fundamental role in managing blood pressure. The cotransporter is targeted by thiazide diuretics, a highly prescribed medication that is effective in treating arterial hypertension and edema. NCC was the first member of the electroneutral cation-coupled chloride cotransporter family to be identified at a molecular level. It was cloned from the urinary bladder of the Pseudopleuronectes americanus (winter flounder) 30 years ago. The structural topology, kinetic and pharmacology properties of NCC have been extensively studied, determining that the transmembrane domain (TM) coordinates ion and thiazide binding. Functional and mutational studies have discovered residues involved in the phosphorylation and glycosylation of NCC, particularly on the N-terminal domain, as well as the extracellular loop connected to TM7-8 (EL7-8). In the last decade, single-particle cryogenic electron microscopy (cryo-EM) has permitted the visualization of structures at high atomic resolution for six members of the SLC12 family (NCC, NKCC1, KCC1-KCC4). Cryo-EM insights of NCC confirm an inverted conformation of the TM1-5 and TM6-10 regions, a characteristic also found in the amino acid-polyamine-organocation (APC) superfamily, in which TM1 and TM6 clearly coordinate ion binding. The high-resolution structure also displays two glycosylation sites (N-406 and N-426) in EL7-8 that are essential for NCC expression and function. In this review, we briefly describe the studies related to the structure-function relationship of NCC, beginning with the first biochemical/functional studies up to the recent cryo-EM structure obtained, to acquire an overall view enriched with the structural and functional aspects of the cotransporter.

CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-ß1 signaling.

Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a deadly disease with limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECIIs. Deficiency of CYB5R3 in AECIIs led to sustained activation of the pro-fibrotic factor TGF-ß1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and the sGC/cGMP/protein kinase G axis that modulates activation of the TGF-ß1 signaling pathway. We demonstrate that sGC agonists (BAY 41-8543 and BAY 54-6544) are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECIIs. Taken together, these results show that CYB5R3 in AECIIs is required to maintain resilience after lung injury and fibrosis and that therapeutic manipulation of the sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.

Genome Sequence Data Reveal at Least Two Distinct Incursions of the Tropical Race 4 Variant of Fusarium Wilt into South America.

The global banana industry is threatened by one of the most devastating diseases: Fusarium wilt of banana. Fusarium wilt of banana is caused by the soilborne fungus Fusarium oxysporum f. sp. cubense (Foc), which almost annihilated the banana production in the late 1950s. A new strain of Foc, known as tropical race 4 (TR4), attacks a wide range of banana varieties, including Cavendish clones, which are the source of 99% of banana exports. In 2019, Foc TR4 was reported in Colombia, and more recently (2021) in Peru. In this study, we sequenced three fungal isolates identified as Foc TR4 from La Guajira (Colombia) and compared them against 19 whole-genome sequences of Foc TR4 publicly available, including four genome sequences recently released from Peru. To understand the genetic relatedness of the Colombian Foc TR4 isolates and those from Peru, we conducted a phylogenetic analysis based on a genome-wide set of single nucleotide polymorphisms (SNPs). Additionally, we compared the genomes of the 22 available Foc TR4 isolates, looking for the presence-absence of gene polymorphisms and genomic regions. Our results reveal that (i) the Colombian and Peruvian isolates are genetically distant, which could be better explained by independent incursions of the pathogen to the continent, and (ii) there is a high correspondence between the genetic relatedness and geographic origin of Foc TR4. The profile of present/absent genes and the distribution of missing genomic regions showed a high correspondence to the clades recovered in the phylogenetic analysis, supporting the results obtained by SNP-based phylogeny.

Epileptic Encephalopathy with Variants in the PHACTR1 and AFF2 Genes: A Case Report.

Developmental and epileptic encephalopathy 70 (DEE70) is an epileptic encephalopathy associated with multiple neurological abnormalities and global developmental delay, among other characteristics. It has recently been established that it is caused by a heterozygous variant of the PHACTR1 gene, with currently four cases reported in the literature. This article presents a case report of a patient with DEE70 with a heterozygous variant in the PHACTR1 gene, who also presents a hemizygous variant in the AFF2 gene, associated with FRAXE syndrome. A phenotypic comparison is made between this case and the four other previously reported cases with variants in the PHACTR1 gene. In addition, the possible participation of the PHACTR1 and AFF2 genes in the clinical characteristics of the individual is discussed.

PredictION: a predictive model to establish the performance of Oxford sequencing reads of SARS-CoV-2.

The optimization of resources for research in developing countries forces us to consider strategies in the wet lab that allow the reuse of molecular biology reagents to reduce costs. In this study, we used linear regression as a method for predictive modeling of coverage depth given the number of MinION reads sequenced to define the optimum number of reads necessary to obtain >200X coverage depth with a good lineage-clade assignment of SARS-CoV-2 genomes. The research aimed to create and implement a model based on machine learning algorithms to predict different variables (e.g., coverage depth) given the number of MinION reads produced by Nanopore sequencing to maximize the yield of high-quality SARS-CoV-2 genomes, determine the best sequencing runtime, and to be able to reuse the flow cell with the remaining nanopores available for sequencing in a new run. The best accuracy was -0.98 according to the R squared performance metric of the models. A demo version is available at https://genomicdashboard.herokuapp.com/.