Nucleobindin-1 modulates extracellular matrix remodeling by promoting intra-Golgi trafficking of matrix metalloproteinase 2

Matrix metalloproteases (MMPs) play a crucial role in tissue homeostasis. Profuse literature has studied their roles in cell migration and tissue invasion during cancer metastasis, as well as in inflammatory processes. Although the literature covering MMPs function is abundant, the intracellular trafficking of these proteins remains poorly understood. The aim of the present work was to identify the molecular mechanism of intracellular trafficking of MMPs, with particular focus on MMP2. A novel mass spectrometry approach revealed nucleobindin-1 (NUCB1), a major regulator of Ca2+ homeostasis at the Golgi, as a potential candidate for the regulation of MMP transport. Using a synchronized cargo trafficking assay, it was possible to demonstrate that in the absence of NUCB1 the intracellular trafficking of MMP2 is delayed. Moreover, this work reveals that NUCB1-dependent MMP2 trafficking is restricted to the Golgi, exclusively delaying its intra-Golgi trafficking at the cis compartment and, as a consequence, decreasing MMP2 mediated cell migration and matrix invasion. Furthermore, my findings show that not only MMP2, but also MT1-MMP intra-Golgi trafficking is impaired, implying that this mechanism could also influence the trafficking of other MMPs. Interestingly, experiments performed with a NUCB1 Ca2+-binding deficient mutant showed that Ca2+ is required, both for the interaction, as well as for proper MMP2 trafficking, suggesting that a specific impairment of cis-Golgi Ca2+ homeostasis, rather than an overall Ca2+ deficiency, is essential for proper MMP2 intra-Golgi trafficking. Taken together the results of this thesis contributed to enlighten the mechanism of MMP2 intracellular trafficking by identifying NUCB1 as a critical player in MMP transport. Importantly, this work highlights the requirement of Ca2+ for proper trafficking, not just at the TGN, as has been documented, but also at the cis-Golgi. Although this is a big step towards the understanding of MMP intracellular trafficking, further investigations are required to gain a better understanding of the retention mechanism of NUCB1 at the cis-Golgi lumen and a deeper insight into the regulation of intra-Golgi protein trafficking

PATRONES DE DIVERSIDAD DE EPÍFITAS EN BOSQUES DE TIERRAS BAJAS Y SUBANDINOS

Tropical rainforests are the most diverse ecosystems on the planet. Although many theories have been proposed to explain their richness we currently know little about their relative importance. This diversity is threatened by anthropogenic disturbances such as fragmentation and forest degradation. In this study we compared epiphytic plant diversity patterns in lowland and subandean forests. More epiphytic diversity was found in subandean (PNN Cueva de los Guácharos) compared to lowland forest (Palmarí Reserve). In addition a higher abundance of epiphytes was found in conserved forest. Tree host diversity was higher in lowland forests than in subandean forests, so we can reject the possibility that differences between the patterns of epiphytic diversity are caused by regional effects of plant diversity. Our results suggest that humidity seems to be the most important environmental filter explaining epiphyte diversity.Los bosques tropicales son los ecosistemas más diversos del planeta y aunque se han propuesto muchas teorías para explicar su riqueza, aún desconocemos gran parte de la importancia relativa de los factores que la afectan. Esta diversidad se encuentra amenazada por alteraciones de origen antrópico, como la fragmentación y la degradación de los bosques. En este estudio se comparan patrones de diversidad de epífitas en un bosque de tierras bajas y uno subandino. De esta manera, se encontró una mayor diversidad de epífitas en el bosque subandino (PNN Cueva de los Guacharos) comparado con el de tierras bajas (reserva Palmarí). Adicionalmente se encontró mayor abundancia de epífitas en los bosques más conservados. Dado que la diversidad de forofitos es mayor en el bosque de tierras bajas que en el subandino, se descarta la posibilidad de que las diferencias en los patrones encontrados se den por efectos regionales de diversidad de plantas. Se concluye que la humedad parece ser el filtro ambiental más importante para explicar la variación en diversidad de epífitas

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

Procesos de subjetivación del género: una experiencia desde la Investigación Basada en Artes

284 p. Libro ElectrónicoPrimera EdicionEste libro, resultado de investigación, fue elaborado en el marco del Convenio Ciencia y Tecnología No. 58 de 2022 suscrito entre el Instituto para la Investigación Educativa y el Desarrollo Pedagógico (IDEP) y la Universidad El Bosque, con el objeto de “Anuar esfuerzos para desarrollar la Investigación Arte, Género y Educación 2022”, en el marco de la Agenda de Investigaciones para la Transformación Pedagógica

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

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 sodium–glucose 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 renin–angiotensin 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

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Todo sabe mejor con ciencia

Notas. Ciencias biológicasLos experimentos permitieron explorar la cocina como laboratorio, haciendo que los cocineros, en un intento por mejorar sus recetas y crear nuevas texturas y sabores, empezaran a aplicar los principios físicoquímicos implicados en la cocina y el equipamiento mismo del laboratorio en sus receta