Cobalamin decyanation by the membrane transporter BtuM.

BtuM is a bacterial cobalamin transporter that binds the transported substrate in the base-off state, with a cysteine residue providing the α-axial coordination of the central cobalt ion via a sulfur-cobalt bond. Binding leads to decyanation of cobalamin variants with a cyano group as the β-axial ligand. Here, we report the crystal structures of untagged BtuM bound to two variants of cobalamin, hydroxycobalamin and cyanocobalamin, and unveil the native residue responsible for the β-axial coordination, His28.

Effects of Hypoxia and Reoxygenation on Metabolic Profiles of Cardiomyocytes.

In vitro cellular models provide valuable insights into the adaptive biochemical mechanisms triggered by cells to cope with the stress situation induced by hypoxia and reoxygenation cycles. The first biological data generated in studies based on this micrometric life-scale has the potential to provide us a global overview about the main biochemical phenomena presented in some reported preconditioning therapies in life-scale of higher dimensions. Thus, in this study, a cell incubator was designed and manufactured to produce a cellular model of heart hypoxia followed by reoxygenation (HfR) through consecutive repetitions of hypoxia-normoxia gas exchange.

Interactions Between Silver Nanoparticles and Culture Medium Biomolecules with Dose and Time Dependencies.

The interaction between silver nanoparticles (AgNPs) and molecules producing coronas plays a key role in cytotoxicity mechanisms. Once adsorbed coronas determine the destiny of nanomaterials in vivo, their effective deployment in the biomedical field requires a comprehensive understanding of the dynamic interactions of biomolecules with nanoparticles. In this work, we characterized 40 nm AgNPs in three different nutritional cell media at different molar concentrations and incubation times to study the binding mechanism of molecules on surface nanoparticles.

Random-walk model of the sodium-glucose transporter SGLT2 with stochastic steps and inhibition.

Random-walk models are frequently used to model distinct natural phenomena such as diffusion processes, stock-market fluctuations, and biological systems. Here, we present a random-walk model to describe the dynamics of glucose uptake by the sodium-glucose transporter of type 2, SGLT2. Our starting point is the canonical alternating-access model, which suggests the existence of six states for the transport cycle.

Random-walk model of cotransport.

We present a statistical mechanical model to describe the dynamics of an arbitrary cotransport system. Our starting point was the alternating access mechanism, which suggests the existence of six states for the cotransport cycle. Then we determined the 14 transition probabilities between these states, including a leak pathway, and used them to write a set of Master Equations for describing the time evolution of the system.

Discriminating aspects of global metabolism of neonatal cardiomyocytes from wild type and KO-CSRP3 rats using proton magnetic resonance spectroscopy of culture media samples.

Knockout of multifunction gene cysteine- and glycine-rich protein 3 (CSRP3) in cardiomyocytes (CMs) of mice leads to heart dilation, severely affecting its functions. In humans, CSRP3 mutations are associated with hypertrophic (HCM) and dilated cardiomyopathy (DCM). The absence of the CSRP3 expression produces unknown effects on in vitro neonatal CMs' metabolism.

Modified 3D Ewald Summation for Slab Geometry at Constant Potential.

We present a new Monte Carlo method to simulate ionic liquids in slab geometry at constant potential. The algorithm is built upon two previous methods while retaining the advantages of each of them. The method is tested against a Poisson-Boltzmann theory and the constant surface charge ensemble, achieving consistency among all of them.

Neurally adjusted ventilatory assist vs. pressure support to deliver protective mechanical ventilation in patients with acute respiratory distress syndrome: a randomized crossover trial.

Background: Protective mechanical ventilation is recommended for patients with acute respiratory distress syndrome (ARDS), but it usually requires controlled ventilation and sedation. Using neurally adjusted ventilatory assist (NAVA) or pressure support ventilation (PSV) could have additional benefits, including the use of lower sedative doses, improved patient-ventilator interaction and shortened duration of mechanical ventilation. We designed a pilot study to assess the feasibility of keeping tidal volume (V) at protective levels with NAVA and PSV in patients with ARDS.

Alterations in cellular force parameters and cell projections in Nasal polyps-derived fibroblasts.

Objective: Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is a disease that features a mechanical dysfunction involving chronic inflammation and altered tissue remodeling. In this study, we aim to evaluate the fibroblast morphology and its cellular traction force in primary fibroblasts cell cultures obtained from both healthy individuals (n=7) and patients with CRSwNP (n=8).

Methods: Using a Traction-force Microscopy we analyzed parameters of Force/Tension in fibroblasts cultures in both experimental groups.

Transport cycle of Escherichia coli lactose permease in a nonhomogeneous random walk model.

We present Monte Carlo simulations for the transport cycle of Escherichia coli lactose permease (LacY), using as a starting point the model proposed by Kaback et al. [Nat. Rev.

Nasal Polyposis: More than a Chronic Inflammatory Disorder-A Disease of Mechanical Dysfunction-The São Paulo Position.

 The importance of our study lies in the fact that we have demonstrated the occurrence of mechanical dysfunction within polypoid tissues, which promotes the development of polyps in the nasal cavity.  To change the paradigm of nasal polyposis (NP). In this new conception, the chronic nasal inflammatory process that occurs in response to allergies, to pollution, to changes in the epithelial barrier, or to other factors is merely the trigger of the development of the disease in individuals with a genetic predisposition to an abnormal tissue remodeling process, which leads to a derangement of the mechanical properties of the nasal mucosa and, consequently, allows it to grow unchecked.

Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells.

Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses.

Quantification of alignment of vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) are essential components that keep the tonus of the arterial network, which is the channel used to conduct the blood from the heart to the peripheral areas of the body. It is known that mechanical and architectural changes in VSMCs may lead to functional modifications in the cardiovascular system; therefore, the quantitative characterization of these changes can help to elucidate questions that remain unclear in pathological situations, such as hypertension, vasospasm, vascular hypertrophy, and atherosclerosis. In this work, we have developed a new framework of image processing using the Sobel operator, associated with statistical analysis, to determine the degree of local alignment of actin filaments, which we found to be directly related with the distensibility of the arterial wall.

Integrated molecular, biochemical, and physiological assessment unravels key extraction method mediated influences on rat neonatal cardiomyocytes.

Neonatal cardiomyocytes are instrumental for disease modeling, but the effects of different cell extraction methods on basic cell biological processes remain poorly understood. We assessed the influence of two popular methods to extract rat neonatal cardiomyocytes, Pre-plating (PP), and Percoll (PC) on cell structure, metabolism, and function. Cardiomyocytes obtained from PP showed higher gene expression for troponins, titin, and potassium and sodium channels compared to PC.

Neurally Adjusted Ventilatory Assist (NAVA) or Pressure Support Ventilation (PSV) during spontaneous breathing trials in critically ill patients: a crossover trial.

Background: Neurally Adjusted Ventilatory Assist (NAVA) is a proportional ventilatory mode that uses the electrical activity of the diaphragm (EAdi) to offer ventilatory assistance in proportion to patient effort. NAVA has been increasingly used for critically ill patients, but it has not been evaluated during spontaneous breathing trials (SBT). We designed a pilot trial to assess the feasibility of using NAVA during SBTs, and to compare the breathing pattern and patient-ventilator asynchrony of NAVA with Pressure Support (PSV) during SBTs.

Non-equilibrium cytoquake dynamics in cytoskeletal remodeling and stabilization.

The cytoskeleton (CSK) is a tensed fiber framework that supports, shapes and stabilizes the cell. The CSK is in a constant state of remodeling, moreover, which is an active non-equilibrium thermodynamic process. We report here that cytoskeletal remodeling involves reconfigurations that are not only sudden but also are transmitted to great distances within the cell in a fashion reminiscent of quakes in the Earth's crust.

Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression.

Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity.

Smoking and Female Sex: Independent Predictors of Human Vascular Smooth Muscle Cells Stiffening.

Aims: Recent evidence shows the rigidity of vascular smooth muscle cells (VSMC) contributes to vascular mechanics. Arterial rigidity is an independent cardiovascular risk factor whose associated modifications in VSMC viscoelasticity have never been investigated. This study's objective was to evaluate if the arterial rigidity risk factors aging, African ancestry, female sex, smoking and diabetes mellitus are associated with VMSC stiffening in an experimental model using a human derived vascular smooth muscle primary cell line repository.

Effects of Oropharyngeal Exercises on Snoring: A Randomized Trial.

Background: Snoring is extremely common in the general population and may indicate OSA. However, snoring is not objectively measured during polysomnography, and no standard treatment is available for primary snoring or when snoring is associated with mild forms of OSA. This study determined the effects of oropharyngeal exercises on snoring in minimally symptomatic patients with a primary complaint of snoring and diagnosis of primary snoring or mild to moderate OSA.

Rapid and Localized Mechanical Stimulation and Adhesion Assay: TRPM7 Involvement in Calcium Signaling and Cell Adhesion.

A cell mechanical stimulation equipment, based on cell substrate deformation, and a more sensitive method for measuring adhesion of cells were developed. A probe, precisely positioned close to the cell, was capable of a vertical localized mechanical stimulation with a temporal frequency of 207 Hz, and strain magnitude of 50%. This setup was characterized and used to probe the response of Human Umbilical Endothelial Vein Cells (HUVECs) in terms of calcium signaling.

Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells.

This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements.

Cardiac mechanics evaluated by speckle tracking echocardiography.

Natural myocardial markers, or speckles, originated from constructive and destructive interference of ultrasound in the tissues may provide early diagnosis of myocardial changes and be used in the prediction of some cardiac events. Due to its relatively temporal stability, speckles can be tracked by dedicated software along the cardiac cycle, enabling the analysis of the systolic and diastolic function. They are identified by either conventional 2D grey scale and by 3D echo, conferring independence of the insonation angle, thus allowing assessment of cardiac mechanics in the three spatial planes: longitudinal, circumferential, and radial.

Diesel exhaust particulates affect cell signaling, mucin profiles, and apoptosis in trachea explants of Balb/C mice.

Particulate matter from diesel exhaust (DEP) has toxic properties and can activate intracellular signaling pathways and induce metabolic changes. This study was conducted to evaluate the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and to analyze the mucin profile (acid (AB(+) ), neutral (PAS(+) ), or mixed (AB/PAS(+) ) mucus) and vacuolization (V) of tracheal explants after treatment with 50 or 100 μg/mL DEP for 30 or 60 min. Western blot analyses showed small increases in ERK1/2 and JNK phosphorylation after 30 min of 100 μg/mL DEP treatment compared with the control.