Results of salt intake restriction monitored with the new sodium control biosensor

Adherence to a low sodium (Na) diet is crucial in patients under hemodialysis, as it improves cardiovascular outcomes and reduces thirst and interdialytic weight gain. Recommended salt intake is lower than 5 g/day. The new 6008 CareSystem monitors incorporate a Na module that offers the advantage of estimating patients' salt intake. The objective of this study was to evaluate the effect of dietary Na restriction for 1 week, monitored with the Na biosensor.A prospective study was conducted in 48 patients who maintained their usual dialysis parameters and were dialyzed with a 6008 CareSystem monitor with activation of the Na module. Total Na balance, pre/postdialysis weight, serum Na (sNa), changes in pre- to post-dialysis sNa (ΔsNa), diffusive balance, and systolic and diastolic blood pressure were compared twice, once after 1 week of patients' usual Na diet and again after another week with more restricted Na intake.Restricted Na intake increased the percentage of patients on a low-sodium diet (<85 Na mmol/day) from 8% to 44%. Average daily Na intake decreased from 149 ± 54 to 95 ± 49 mmol and interdialytic weight gain was reduced by 460 ± 484 g per session. More restricted Na intake also decreased pre-dialysis sNa and increased both intradialytic diffusive balance and ΔsNa. In hypertensive patients, reducing daily sodium by more than 3 g Na/day lowered their systolic blood pressure.The new Na module allowed objective monitoring of Na intake, which in turn could permit more precise personalized dietary recommendations in patients under hemodialysis.S. Karger AG, Basel

The effects of intermittent hypoxia training on hematological and aerobic performance in triathletes

The aim of the present research was to analyze modifications on hematological and aerobic performance parameters after a 7-week intermittent hypoxia training (IHT) program. Eighteen male trained triathletes were divided in two groups: an intermittent hypoxia training group (IHTG: n: 9; 26.0 ± 6.7 years; 173.3 ± 5.9 cm; 66.4 ± 5.9 kg; VO2max: 59.5 ± 5.0 ml/kg/min) that conducted a normoxic training plus an IHT and a control group (CG: n: 9; 29.3 ± 6.8 years; 174.9 ± 4.6 cm; 59.7 ± 6.8 kg; VO2max: 58.9 ± 4.5 ml/kg/min) that performed only a normoxic training. Training process was standardized across the two groups. The IHT program consisted of two 60-min sessions per week at intensities over the anaerobic threshold and atmospheric conditions between 14.5 and 15% FiO2. Before and after the 7-week training, aerobic performance in an incremental running test and hematological parameters were analyzed. After this training program, the IHTG showed higher hemoglobin and erythrocytes (p < 0.05) values than in the CG. In terms of physiological and performance variables, between the two groups no changes were found. The addition of an IHT program to normoxic training caused an improvement in hematological parameters but aerobic performance and physiological variables compared to similar training under normoxic conditions did not increase

ER-Bound Protein Tyrosine Phosphatase PTP1B Interacts with Src at the Plasma Membrane/Substrate Interface

PTP1B is an endoplasmic reticulum (ER) anchored enzyme whose access to substrates is partly dependent on the ER distribution and dynamics. One of these substrates, the protein tyrosine kinase Src, has been found in the cytosol, endosomes, and plasma membrane. Here we analyzed where PTP1B and Src physically interact in intact cells, by bimolecular fluorescence complementation (BiFC) in combination with temporal and high resolution microscopy. We also determined the structural basis of this interaction. We found that BiFC signal is displayed as puncta scattered throughout the ER network, a feature that was enhanced when the substrate trapping mutant PTP1B-D181A was used. Time-lapse and co-localization analyses revealed that BiFC puncta did not correspond to vesicular carriers; instead they localized at the tip of dynamic ER tubules. BiFC puncta were retained in ventral membrane preparations after cell unroofing and were also detected within the evanescent field of total internal reflection fluorescent microscopy (TIRFM) associated to the ventral membranes of whole cells. Furthermore, BiFC puncta often colocalized with dark spots seen by surface reflection interference contrast (SRIC). Removal of Src myristoylation and polybasic motifs abolished BiFC. In addition, PTP1B active site and negative regulatory tyrosine 529 on Src were primary determinants of BiFC occurrence, although the SH3 binding motif on PTP1B also played a role. Our results suggest that ER-bound PTP1B dynamically interacts with the negative regulatory site at the C-terminus of Src at random puncta in the plasma membrane/substrate interface, likely leading to Src activation and recruitment to adhesion complexes. We postulate that this functional ER/plasma membrane crosstalk could apply to a wide array of protein partners, opening an exciting field of research

Near-Membrane Dynamics and Capture of TRPM8 Channels within Transient Confinement Domains

The cold and menthol receptor, TRPM8, is a non-selective cation channel expressed in a subset of peripheral neurons that is responsible for neuronal detection of environmental cold stimuli. It was previously shown that members of the transient receptor potential (TRP) family of ion channels are translocated toward the plasma membrane (PM) in response to agonist stimulation. Because the spatial and temporal dynamics of cold receptor cell-surface residence may determine neuronal activity, we hypothesized that the movement of TRPM8 to and from the PM might be a regulated process. Single particle tracking (SPT) is a useful tool for probing the organization and dynamics of protein constituents in the plasma membrane.We used SPT to study the receptor dynamics and describe membrane/near-membrane behavior of particles containing TRPM8-EGFP in transfected HEK-293T and F-11 cells. Cells were imaged using total internal reflection fluorescence (TIRF) microscopy and the 2D and 3D trajectories of TRPM8 molecules were calculated by analyzing mean-square particle displacement against time. Four characteristic types of motion were observed: stationary mode, simple Brownian diffusion, directed motion, and confined diffusion. In the absence of cold or menthol to activate the channel, most TRPM8 particles move in network covering the PM, periodically lingering for 2–8 s in confined microdomains of about 800 nm radius. Removing cholesterol with methyl-beta-cyclodextrin (MβCD) stabilizes TRPM8 motion in the PM and is correlated with larger TRPM8 current amplitude that results from an increase in the number of available channels without a change in open probability.These results reveal a novel mechanism for regulating TRPM8 channel activity, and suggest that PM dynamics may play an important role in controlling electrical activity in cold-sensitive neurons

FAK/src-Family Dependent Activation of the Ste20-Like Kinase SLK Is Required for Microtubule-Dependent Focal Adhesion Turnover and Cell Migration

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal

Revisiting the dimensional structure of the Edinburgh Postnatal Depression Scale (EPDS): empirical evidence for a general factor

<p>Abstract</p> <p>Background</p> <p>The Edinburgh Postnatal Depression Scale (EPDS) has been proposed as a one-dimensional instrument and used as a single 10-item scale. This might be considered questionable since repeated psychometric studies have shown multi-dimensionality, which would entail using separate component subscales. This study reappraised the dimensional structure of the EPDS, with a focus on the extent of factor correlations and related factor-based discriminant validity as a foundation for deciding how to effectively scale the component items.</p> <p>Methods</p> <p>The sample comprised 811 randomly selected mothers of children up to 5 months attending primary health services of Rio de Janeiro, Brazil. Strict Confirmatory Factor Analysis (CFA) and Exploratory Factor Analysis modeled within a CFA framework (E/CFA) were sequentially used to identify best fitting and parsimonious model(s), including a bifactor analysis to evaluate the existence of a general factor. Properties concerning the related 10-item raw-score scale were also investigated using non-parametric items response theory methods (scalability and monotonicity).</p> <p>Results</p> <p>An initial CFA rejected the one-dimensional structure, while an E/CFA subscribed a three-dimensional solution. Yet, factors were highly correlated (0.66, 0.75 and 0.82). The ensuing CFA showed poor discriminant validity (some square-roots of average variance extracted below the factor correlations). A general bifactor CFA was then fit. Results suggested that, although still weakly encompassing three specific factors, the EPDS might be better described by a model encompassing a general factor (loadings ranging from 0.51 to 0.81). The related 10-item raw score showed adequate scalability (Loevinger's H coefficient = 0.4208), monotonicity e partial double monotonicity (nonintersections of Item Step Response Functions).</p> <p>Conclusion</p> <p>Although the EPDS indicated the presence of specific factors, they do not qualify as independent dimensions if used separately and should therefore not be used empirically as sub-scales (raw scores). An all-encompassing scale seems better suited and continuing its use in clinical practice and applied research should be encouraged.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta