224 research outputs found

    Determination of protein-protein interactions at the single-molecule level using optical tweezers

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    Biomolecular interactions are at the base of all physical processes within living organisms; the study of these interactions has led to the development of a plethora of different methods. Among these, single-molecule (in singulo) experiments have become relevant in recent years because these studies can give insight into mechanisms and interactions that are hidden for ensemble-based (in multiplo) methods. The focus of this review is on optical tweezer (OT) experiments, which can be used to apply and measure mechanical forces in molecular systems. OTs are based on optical trapping, where a laser is used to exert a force on a dielectric bead; and optically trap the bead at a controllable position in all three dimensions. Different experimental approaches have been developed to study protein-protein interactions using OTs, such as: (1) refolding and unfolding in trans interaction where one protein is tethered between the beads and the other protein is in the solution; (2) constant force in cis interaction where each protein is bound to a bead, and the tension is suddenly increased. The interaction may break after some time, giving information about the lifetime of the binding at that tension. And (3) force ramp in cis interaction where each protein is attached to a bead and a ramp force is applied until the interaction breaks. With these experiments, parameters such as kinetic constants (koff, kon), affinity values (KD), energy to the transition state ΔG≠, distance to the transition state Δx≠ can be obtained. These parameters characterize the energy landscape of the interaction. Some parameters such as distance to the transition state can only be obtained from force spectroscopy experiments such as those described here

    COVID-19 and dengue coinfection in Latin America: A systematic review

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    "Introduction: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally, becoming a long-lasting pandemic. Dengue is the most common arboviral disease in tropical and subtropical regions worldwide. COVID-19 and dengue coinfections have been reported, associated with worse outcomes with significant morbidity and mortality. Therefore, this study aims to determine the epidemiological situation of COVID-19 and dengue coinfection in Latin America. Methods: A systematic literature review was performed using PubMed, Scopus, Embase, Web of Science, LILACS, and BVS databases from January 1, 2020, to September 4, 2021. The key search terms used were ""dengue"" and ""COVID-19"". Results: Nineteen published articles were included. The studies were case reports with a detailed description of the coinfection’s clinical, laboratory, diagnostic, and treatment features. Conclusion: Coinfection with SARS-CoV-2 and dengue virus is associated with worse outcomes with significant morbidity and mortality. The similar clinical and laboratory features of each infection are a challenge in accurately diagnosing and treating cases. Establishing an early diagnosis could be the answer to reducing the estimated significant burden of these conditions.

    Caracterización de pacientes con prediabetes en instituciones de servicio de salud de primer nivel en Cali, Colombia

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    Introduction: Type 2 diabetes (DM 2) is one of the first ten causes of mortality in Colombia. Pre-diabetes is a state of hyperglycemia that associated with other risk factors appears 5-10 years before this disease. It has been reported that controlling the diet and exercise decreases the probability of suffering DM 2 by 60%. This intervention requires establishing the risk in pre-diabetic patients. Objectives: To detect patients with pre-diabetes who are members of a private health care provider (EPS for its name in Spanish) in Cali and to describe the clinical and epidemiological characteristics related to the risk of developing DM 2. Materials and methods: This is a cross-sectional descriptive study in patients with altered glucemias (Impaired fasting glucose: 100-125 mg/dl and impaired glucose tolerance: 140-199 mg/dl). Clinical histories were reviewed and surveys on risk factors, habits and perception of knowledge were conducted. We determined: fasting glucose, vital signs, and anthropometric measures. Results: 111 patients were included (64% women) whose most common occupation was home duties (39.6%). The descriptive analysis reported high risk; the results were: noticeable presence of associate pathological antecedents as follows: Diabetes in the family (64%), obesity (54.1%), dyslipidemia (72.1%), and hypertension (66.7%) in a population with a mean age at 51 years and 10.8% were under 40 years of age. This great proportion of overweight or obesity (86.5%), according to BMI, influenced the determination of the high cardio-metabolic risk (81%, agreeing with the WHO). When evaluating diet with consumption frequency, we still found the intake of simple carbohydrates and animal fats; when reviewing physical activity, 53.2% of the patients reported activity in the last 7 days according to the International Physical Activity Questionnaire (IPAQ). Conclusions: 66% of pre-diabetics did not have diagnosis of some disorder of the metabolism of carbohydrates. More than 70% of the patients have high risk of DM 2 with pathological antecedents, inadequate health habits, and low perception of disease complications. Introducción: La diabetes tipo 2 (DM 2) es una de las diez primeras causas de mortalidad en Colombia. La prediabetes es un estado de hiperglucemia que, asociado con otros factores de riesgo, se presenta 5-10 años antes de dicha enfermedad. Se ha informado que controlar la dieta y el ejercicio disminuye la probabilidad de padecer DM 2 hasta en 60%. Identificar y caracterizar el riesgo en los pacientes prediabéticos contribuye en la prevención de la DM 2. Objetivos: Detectar los pacientes con prediabetes afiliados a una EPS privada de Cali, evaluar y describir su estado de riesgo. Materiales y métodos: Se realizó estudio descriptivo transversal en pacientes con glucemias alteradas (glucemia en ayunas, 100-125 mg/dl y glucemia post-carga, 140-199 mg/dl). Se revisaron historias clínicas y se realizó encuesta de factores de riesgo, hábitos y percepción de conocimientos. Se determinaron glucemia en ayunas, signos vitales y medidas antropométricas. Resultados: Se incluyeron 111 pacientes (64% mujeres), con edad promedio de 51 años y 10.8% menor de 40 años, cuya mayor ocupación fue el hogar (39.6%). Se encontró alto riesgo para desarrollar DM 2 de acuerdo con los siguientes resultados: alta proporción de antecedentes patológicos asociados como diabetes familiar (64%), obesidad (54.1%), dislipidemias (72.1%) e hipertensión (66.7%). La gran proporción de sobrepeso u obesidad según IMC hallado (86.5%), influyó en la determinación del alto riesgo cardiometabólico (81% según criterios de la OMS). Al evaluar dieta con frecuencia de consumo, se encontró todavía ingesta de carbohidratos simples y grasas animales; luego de revisar actividad física, 53.2% informó actividad en la semana antes del Cuestionario Internacional de Actividad Física (IPAQ). Conclusiones: Del total de los prediabéticos, 66% no tenía diagnóstico de algún desorden del metabolismo de los carbohidratos. Más del 70% de los pacientes tiene alto riesgo de DM 2 con hábitos saludables inadecuados y baja percepción de las complicaciones

    Oscillatory surface rheotaxis of swimming E. coli bacteria

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    Bacterial contamination of biological conducts, catheters or water resources is a major threat to public health and can be amplified by the ability of bacteria to swim upstream. The mechanisms of this rheotaxis, the reorientation with respect to flow gradients, often in complex and confined environments, are still poorly understood. Here, we follow individual E. coli bacteria swimming at surfaces under shear flow with two complementary experimental assays, based on 3D Lagrangian tracking and fluorescent flagellar labelling and we develop a theoretical model for their rheotactic motion. Three transitions are identified with increasing shear rate: Above a first critical shear rate, bacteria shift to swimming upstream. After a second threshold, we report the discovery of an oscillatory rheotaxis. Beyond a third transition, we further observe coexistence of rheotaxis along the positive and negative vorticity directions. A full theoretical analysis explains these regimes and predicts the corresponding critical shear rates. The predicted transitions as well as the oscillation dynamics are in good agreement with experimental observations. Our results shed new light on bacterial transport and reveal new strategies for contamination prevention.Comment: 12 pages, 5 figure

    Results from the Super Cryogenic Dark Matter Search (SuperCDMS) experiment at Soudan

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    We report the result of a blinded search for Weakly Interacting Massive Particles (WIMPs) using the majority of the SuperCDMS Soudan dataset. With an exposure of 1690 kg days, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP--nucleon cross section of 1.4×10441.4 \times 10^{-44} (1.0×10441.0 \times 10^{-44}) cm2^2 at 46 GeV/c2c^2. These results set the strongest limits for WIMP--germanium-nucleus interactions for masses >>12 GeV/c2c^2

    Zero-Branes, Quantum Mechanics and the Cosmological Constant

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    We analyse some dynamical issues in a modified type IIA supergravity, recently proposed as an extension of M-theory that admits de Sitter space. In particular we find that this theory has multiple zero-brane solutions. This suggests a microscopic quantum mechanical matrix description which yields a massive deformation of the usual M(atrix) formulation of M-theory and type IIA string theory.Comment: 15 pages LaTeX, added reference

    Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry

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    OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies
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