Yra1-bound RNA–DNA hybrids cause orientation-independent transcription– replication collisions and telomere instability

R loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess causes lethality and genome instability. Here, we show that, in addition to ssDNA and ssRNA, Yra1 binds RNA–DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA– DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo. Importantly, an excess of Yra1 increases R-loop-mediated genome instability caused by transcription–replication collisions regardless of whether they are codirectional or head-on. It also induces telomere shortening in telomerase-negative cells and accelerates senescence, consistent with a defect in telomere replication. Our results indicate that RNA–DNA hybrids form transiently in cells regardless of replication and, after stabilization by excess Yra1, compromise genome integrity, in agreement with a two-step model of R-loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.European Research Council ERC2014 AdG669898 TARLOOPMinisterio de Economía y Competitividad BFU2016-75058-PJunta de Andalucía PA12- BIO123

Development and Testing of a Real-Time LoRawan Sniffer Based on GNU-Radio

En este documento se muestran las vulnerabilidades presentes en una red de sensores inalámbricas implementada sobre una red de área amplia de largo alcance (LoRaWAN por sus siglas en inglés) LoRaWAN y se identifican los posibles ataques que se podrían realizar a la red usando sniffing y/o replay. Los ataques a la red se realizaron implementando un analizador de protocolos (Sniffer) para capturar los paquetes. El Sniffer se implementó utilizando el hardware RTL2832U y se visualizó en Wireshark, a través de GNU-Radio. Las pruebas mostraron que se pueden amenazar la disponibilidad y confidencialidad de los datos a través de ataques de replay con verificación en el LoRa server utilizando hardware HackRF One y GNU-Radio. Aunque la especificación LoRaWAN tiene contadores para evitar ataques de replay, bajo condiciones adecuadas se lograría vulnerar la red llegando a realizar la denegación del servicio del nodo en el servidor.This paper shows the vulnerabilities present in a wireless sensor network implemented over a long-range wide area network (LoRaWAN) LoRaWAN, and identifies possible attacks that could be made to the network using sniffing and/or replay. Attacks on the network were performed by implementing a protocol analyzer (Sniffer) to capture packets. The Sniffer was implemented using the RTL2832U hardware and visualized in Wireshark, through GNU-Radio. Tests showed that data availability and confidentiality could be threatened through replay attacks with LoRa server verification using HackRF One and GNU-Radio hardware. Although the LoRaWAN specification has, frame counters to avoid replay attacks, under given the right conditions, this measure could be violated even deny service to the node on the server

Evaluation of the Naïve Bayes clasificator as a tool of diagnosisin the intensive care units

En el proceso de diagnóstico médico se busca identificar el estado de salud de un paciente. Sin embargo, la complejidad fisiológica del ser humano genera una amplia gama de condiciones difíciles de establecer por el personal médico en pacientes patológicos. En las unidades de cuidado intensivo, donde habitualmente se utiliza la ventilación asistida, se presenta un alto grado de incertidumbre a la hora de identificar el momento adecuado de retirar el ventilador mecánico. Teniendo en cuenta esta problemática, presentamos el diseño y evaluación de una herramienta basada en inferencia bayesiana que brinda información al médico sobre la viabilidad de tener una extubación exitosa. Para su diseño y validación se utilizó una base de datos con señales de flujo respiratorio compuesta por 98 pacientes exitosamente extubados, y 38 que fracasaron. Las señales fueron caracterizadas inicialmente con un grupo de series temporales, y posteriormente, el patrón respiratorio en los dos grupos de estudio fue analizado con técnicas estadísticas y de modelado autorregresivo. De este último proceso se derivo un grupo de variables con las cuales se diseñó un clasificador tipo Naive Bayes. Los resultados fueron medidos en función de la exactitud, sensibilidad y especificidad del clasificador, logrando un 78% en la primera medida y un 75% y 74% en las dos segundas.In the process of medical diagnosis is to identify the health status of a patient. However, the complexity of the human physiological generates a variety of difficult conditions set by the medical staff in each patient. A high degree of uncertainty comes to identifying the right time to begin the withdrawal of mechanical ventilation in Intensive Care Units. Considering this problem, we present the design and evaluation of a Bayesian inference based tool that provides information to the physician about the feasibility of having a successful extubation. For design and validation database with respiratory flow signals composed successfully extubated 98 patients, 38 who failed was used. The signals were initially characterized with a group of time series, and then the breathing pattern in the two study groups was analyzed with statistical techniques and autoregressive modeling. This latter process a group of variables with which a Naive Bayes classifier type design was derived. Results were measured in terms of exactitude, sensitivity and specificity of the classifier, achieving 78% in the first step and 75% and 74% in the second two

Evaluation of sustainability of the production of biofuels of the second generation by means of the application of Analysis Exergy

El acelerado desarrollo en los últimos años de la industria del bioetanol en Colombia y América Latina ha generado como consecuencia un posterior debate sobre sus impactos ambientales, energéticos y el uso de cultivos de uso alimenticio para su producción. Debido a esto, los esfuerzos en el desarrollo de biocombustibles se han enfocado en la búsqueda de nuevas materias primas y el análisis de las tecnologías de producción desde el punto de vista energético y ambiental, que permitan alcanzar el desarrollo sostenible de esta industria. El uso de residuos lignocelulósicos para la producción de biocombustibles, representa una mejor alternativa que los cultivos energéticos tradicionales, ya que no es usado como alimento y en muchos casos representan un problema asociado a su disposición. Así, para asegurar el desarrollo sostenible de los biocombustibles de segunda generación, es necesario confirmar que el consumo energético del proceso global sea menor que la energía obtenida por el uso del biocombustible producido. De esta manera, el análisis exergético representa una gran herramienta que permite evaluar la eficiencia global del proceso, al tiempo que se determinan las etapas que requieren mejoras. En este trabajo, el bagazo de caña ha sido utilizado como materia prima para la producción de biocombustibles de segunda generación. El análisis exergético ha sido usado como herramienta para evaluar la eficiencia y sostenibilidad del proceso de producción de segunda generación. Como caso de estudio, se han evaluado dos esquemas de producción usando como base la utilización de 1200 toneladas diarias de bagazo de caña los cuales fueron simulados usando ASPEN-HYSYS® y software desarrollado por los autores. Con base en los resultados obtenidos han sido identificadas las etapas que requieren mejoras tecnológicas y ha sido analizada la sostenibilidad de las tecnologías analizadas en la industria colombiana.Abstract: The rapid development of the bioethanol industry in Colombia and LatinAmerica sparked a “food versus fuel” debate and further speculation about the industry’s environmental impact. However, lignocellulosic biomass is a great alternative because it utilizes waste resources and, therefore, does not compete with food crops. To ensure the sustainability of the production of second generation biofuels, it is necessary to confirm that the energy content of biofuels produced from lignocellulosic biomass is significantly greater than the energy consumed in the process. Exergy analysis serves as a unified and effective tool to evaluate the global process efficiency. As bagasse does not jeopardize the food supply, this paper analyzes the integration of sugarcane bagasse as a raw material for second generation biofuels production. Exergy analysis evaluates the performance of sugarcane bagasse and its sustainability in the bioethanol production process. This case study implements a design and process integration to compare two biorefinery topologies using the typical daily amount of residual biomass produced by the sugar industry (1,200 tonnes). Based on results, the stages with most need of improvement were identified and the sustainability of technologies in Colombia was analyzed. This study was executed by the use of the ASPEN-HYSYS® program and other software developed by the authors

Toxic Determination of Cry11 Mutated Proteins Obtained Using Rational Design and Its Computational Analysis

Cry11 proteins are toxic to Aedes aegypti, the vector of dengue, chikungunya, and Zika viruses. Cry11Aa and Cry11Bb are protoxins, which when activated present their active-toxin form in two fragments between 30 and 35 kDa respectively. Previous studies conducted with Cry11Aa and Cry11Bb genes using DNA shuffling generated variant 8, which presented a deletion in the first 73 amino acids and one at position 572 and 9 substitutions including L553F and L556W. In this study, variant 8 mutants were constructed using site-directed mutagenesis, resulting in conversion of phenylalanine (F) and tryptophan (W) to leucine (L) at positions 553 and 556, respectively, producing the mutants 8F553L, 8W556L, and 8F553L/8W556L. Additionally, two mutants, A92D and C157R, derived from Cry11Bb were also generated. The proteins were expressed in the non-crystal strain BMB171 of Bacillus thuringiensis and subjected to median-lethal concentration (LC 50) tests on first-instar larvae of A. aegypti. LC 50 analysis showed that the 8F553L, 8W556L, 8F553L/8W556L, and C157R variants lost their toxic activity (&gt;500 ng·mL -1), whereas the A92D protein presented a loss of toxicity of 11.4 times that of Cry11Bb. Cytotoxicity assays performed using variant 8, 8W556L and the controls Cry11Aa, Cry11Bb, and Cry-negative BMB171 on the colorectal cancer cell line SW480 reported 30-50% of cellular viability except for BMB171. Molecular dynamic simulations performed to identify whether the mutations at positions 553 and 556 were related to the stability and rigidity of the functional tertiary structure (domain III) of the Cry11Aa protein and variant 8 showed the importance of these mutations in specific regions for the toxic activity of Cry11 against A. aegypti. This generates pertinent knowledge for the design of Cry11 proteins and their biotechnological applications in vector-borne disease control and cancer cell lines. </p

Renal vasculitis in Colombia

A retrospective review of publications about primary vasculitis cases was performed from the Colombian medical literature, the clinical and pathological features are described.The Renal vasculitis occurred in 33.9% of cases of primary vasculitis reviewed and was more frequent in women. The main clinical, hematological, immunological variables and nephropathology and immunosuppressive treatments used findings are described

Clinical factors associated with high glycemic variability defined by coefficient of variation in patients with type 2 diabetes

Antecedentes: La Variabilidad Glucémica Alta (VHG) ha convertirse en un predictor más fuerte de hipoglucemia. Sin embargo, aún se desconocen los factores clínicos asociados con el VHG. Objetivo:Determinar las variables clínicas que se asociaron con un coeficiente de variación (CV) superior al 36% evaluado mediante monitorización continua de glucosa (MCG) en un grupo de pacientes con diabetes mellitus. Métodos: Se evaluó una cohorte de pacientes con diabetes tipo 2 (T2D). Se evaluaron variables demográficas, HbA1c, tasa de filtración glomerular (TFG) y régimen de tratamiento. Se realizó un análisis bivariado, para evaluar la asociación entre la variable resultado (CV > 36%) y cada una de las variables independientes. Se construyó un modelo multivariado para evaluar las asociaciones después de controlar las variables de confusión. Resultados:Se analizaron los datos de MCG de 274 pacientes. CV> 36% estuvo presente en 56 pacientes (20,4%). En el análisis bivariado se incluyeron variables demográficas y clínicas, como tiempo desde el diagnóstico, antecedente de hipoglucemia, A1c, FG y tratamiento instaurado. En el análisis multivariante, FG 9% (OR 2,81; IC 1,05,7,51; p:0,04) y antecedentes de hipoglucemia (OR 2,09; IC 1,02, 4,32; p: 0,04) se asociaron con VHG. El tratamiento con iDPP4 (OR 0,39; IC 0,19, 0,82; p: 0,01) y AGLP1 (OR 0,08; IC 0,01, 0,68; p: 0,02) se asoció inversamente con la VG. Conclusión:Variables clínicas como FG 9% y antecedentes de hipoglucemia se asocian a un VG alto. Nuestros datos sugieren que el uso de tecnología y tratamientos capaces de reducir la variabilidad glucémica podría ser útil en esta población para reducir el riesgo de hipoglucemia y mejorar el control glucémico.Q3Background: High glycemic Variability (HGV) has become a stronger predictor of hypoglycemia. However, clinical factors associate with HGV still are unknown. Objective: To determine clinical variables that were associated with a coefficient of variation (CV) above 36% evaluated by continuous glucose monitoring (CGM) in a group of patients with diabetes mellitus. Methods: A cohort of patients with type 2 diabetes (T2D) was evaluated. Demographic variables, HbA1c, glomerular filtration rate (GFR) and treatment regimen were assessed. A bivariate analysis was performed, to evaluate the association between the outcome variable (CV> 36%) and each of the independent variables. A multivariate model was constructed to evaluate associations after controlling for confounding variables. Results: CGM data from 274 patients were analyzed. CV> 36% was present in 56 patients (20.4%). In the bivariate analysis, demographic and clinical variables were included, such as time since diagnosis, hypoglycemia history, A1c, GFR and treatment established. In the multivariate analysis, GFR 9% (OR 2.81; CI 1.05,7.51; p:0.04) and hypoglycemia history (OR 2.09; CI 1.02,4.32; p:0.04) were associated with HGV. Treatment with iDPP4 (OR 0.39; CI 0.19,0.82; p:0.01) and AGLP1 (OR 0.08; CI 0.01,0.68; p:0.02) was inversely associated with GV. Conclusion: Clinical variables such as GFR 9% and a history of hypoglycemia are associated with a high GV. Our data suggest that the use of technology and treatments able to reduce glycemic variability could be useful in this population to reduce the risk of hypoglycemia and to improve glycemic control.Revista Internacional - Indexad

Comparison of the pulmonary function of patients with type 2 diabetes mellitus treated with insulin injections versus that of patients treated with oral hypoglucemic agents

Introducción: la potencial asociación entre el tipo de tratamiento de la diabetes mellitus tipo 2 (DM2) y alteración de la función pulmonar es algo poco estudiado hasta ahora. Objetivos: comparar la función pulmonar de pacientes con DM2 que reciben tratamiento con insulina inyectable versus hipoglicemiantes orceles (HO). Determinar si niveles de marcadores de inflamación en pacientes con tratamiento basado en insulina son diferentes a los de los tratados con HO. Métodos: estudio observational analítico de corte transversal a partir de una muestra de conveniencia de 369 pacientes con diagnóstico de DM2, y tratamiento con insulina o HO. Se realizaron espirometrías, y se obtuvieron valores residuales promedios para VEF1, CVF y relación VEF1/CVF. Mediante regresión lineal múltiple, se ajustó por diferencias en determinantes conocidos de la función pulmonar, así como por control de la diabetes y tiempo desde el diagnóstico. Adicionalmente, se midieron niveles de marcadores inflamatorios sanguíneos para cada grupo de tratamiento. Resultados: 63 pacientes (17%) recibían tratamiento con insulina y 306 (83%) con HO. La diferencia en residuales faxoreció a los tratados con HO. Para VEF1, CVF y VEF1/CVF la diferencia fue 57.6 mL (IC95% 32.45-82.74; P 0.0047), 45.6 mL (IC95% 20.84-70.39; P 0.0231) y 0.017, (IC95% 0.01-0.02, PcO.0001), respectivamente. No hubo cambios estadísticamente significativos en marcadores de inflamación. Conclusiones: los pacientes en tratamiento con HO presentaron mejor función pulmonar que los tratados con insulina. Este hallazgo de diferencias en función pulmonar pudiera tener implicación clínica en el manejo de los pacientes diabéticos, pero debe confirmarse en estudios prospectivos.Artículo original113-118Introduction: the potential association between the type of treatment of type 2 diabetes mellitus (DM2) and impaired lung function is something rarely studied so far. Objectives: to compare the lung function of patients with DM2 who are treated with injectable insulin versus HO. To determine whether levels of inflammatory markers in patients with insulin-based treatment are different from those treated with HO. Methods: an observational, analytical, cross-sectional study from a convenience sample of 369 patients diagnosed with DM2 and treated with insulin or HO. Spirometry was performed, and residual values were averaged for FEV1, FVC and FEV1/FVC ratios. Multiple linear regression results were adjusted by differences in known determinants of lung function, as well as control of diabetes and time since diagnosis. Additionally, we measured blood levels of inflammatory markers for each treatment group. Results: 63 patients (17%) were treated with insulin and 306 (83%) with OH. The difference in residual favored those treated with HO. For FEV1, FVC and FEV1/FVC the difference was 57.6 mL (95% CI 32.45 to 82.74, P 0.0047), 45.6 mL (95% CI 20.84 to 70.39, P 0.0231) and 0.017 (95% CI 0.01 to 0.02, P <0.0001), respectively. There were no statistically significant changes in inflammation markers. Conclusions: patients treated with HO showed better lung function than those treated with insulin. This finding of differences in lung function may have clinical implications in the management of diabetic patients, but needs to be confirmed in prospective studies

Nature-based solutions and carbon dioxide removal

The negative impacts of climate change call for an urgent global response, to mitigate emissions and strengthen the adaptive capacity of social, economic, and environmental structures. In Latin America and the Caribbean, in a context of high vulnerability and three simultaneous crises affecting the region, development models need to be transformed, to bring about a sustainable transition. During this process, national and local policies must harness the full potential of climate action, through adoption of new technologies, innovation, productive reorganization, and identification of synergies. This is why nature-based solutions and carbon dioxide removal measures and technologies are critical to achieving climate goals. Against this backdrop, this paper examines the opportunities and challenges of large-scale implementation of such measures in the region, emphasizing the need to accelerate ongoing efforts, expand the research frontier and manage risks.Abstract .-- Introduction .-- I. Greenhouse gas emission reduction targets and Nationally Determined Contributions. The problem of insufficiency and global climate targets .-- II. Carbon dioxide removal measures and technologies, and their relevance to Latin America and the Caribbean: regional overview, challenges, and opportunities .-- III. The problem of land degradation and desertification. Deforestation: the global context with a focus on Latin America and the Caribbean .-- IV. Carbon Dioxide Removal: techniques and rationales .-- V. Some CDR governance agenda for global consideration .-- VI. Case study: impact of carbon dioxide removal measures and/or technologies on sustainable development objectives in Latin America and the Caribbean .-- VII. Conclusion