Calcium Sensing by Recoverin : Effect of Protein Conformation on Ion Affinity

The detailed functional mechanism of recoverin, which acts as a myristoyl switch at the rod outer-segment disk membrane, is elucidated by direct and replica-exchange molecular dynamics. In accord with NMR structural evidence and calcium binding assays, simulations point to the key role of enhanced calcium binding to the EF3 loop of the semiopen state of recoverin as compared to the closed state. This 2-4-order decrease in calcium dissociation constant stabilizes the semiopen state in response to the increase of cytosolic calcium concentration in the vicinity of recoverin. A second calcium ion then binds to the EF2 loop and, consequently, the structure of the protein changes from the semiopen to the open state. The latter has the myristoyl chain extruded to the cytosol, ready to act as a membrane anchor of recoverin.Peer reviewe

From first‐trimester screening to risk stratification of evolving pre‐eclampsia in second and third trimesters of pregnancy: comprehensive approach

Preeclampsia and associated hypertensive disorders of pregnancy represent a leading cause of global maternal and neonatal morbidity and mortality. Identification of women at high risk for developing preterm-preeclampsia and prophylaxis with low-dose aspirin has the potential to significantly reduce the rate of preterm-preeclampsia. In addition, risk assessment and monitoring of women in the second and third trimester of pregnancy, to aid in early detection of evolving disease, timely referral to specialist care, and active monitoring of women with confirmed or suspected preeclampsia is essential for improving maternal and neonatal outcomes. The angiogenesis-related biomarkers sFlt-1 and PlGF have been shown to have clinical value to aid in the prediction, diagnosis, and risk stratification of preeclampsia when used either alone or in combination with other risk factors. However, currently there is no consensus on the optimum strategy to link first trimester screening for preterm-preeclampsia with appropriate second and third trimester risk assessment strategies. This opinion paper will outline the current evidence for first trimester preeclampsia screening and prevention, as well as the evidence for various risk stratification approaches for detection of evolving preeclampsia through the second and third trimesters of pregnancy, and proposes a potential model integrating these tools. This article is protected by copyright. All rights reserved

Simultaneous bilateral or unilateral carpal tunnel release? A prospective cohort study of early outcomes and limitations

BACKGROUND: Over 60% of patients with carpal tunnel syndrome present with symptoms and findings of nerve compression in both hands. Our goal was to compare patient-rated difficulties in performing activities of daily living in the early postoperative period between those undergoing bilateral carpal tunnel release and those undergoing unilateral carpal tunnel release. METHODS: This prospective cohort study enrolled consecutive patients with bilateral carpal tunnel syndrome undergoing bilateral carpal tunnel release (n = 47) or unilateral carpal tunnel release (n = 41). Patient function and disease severity were measured by an abbreviated form of the Disabilities of the Arm, Shoulder and Hand questionnaire, QuickDASH, and the Boston Carpal Tunnel Questionnaire at baseline, at postoperative visit 1 at a mean time (and standard deviation) of 10 ± 3 days, and at postoperative visit 2 at a mean time (and standard deviation) of 30 ± 6 days. Patients rated their difficulty in completing fifteen activities of daily living each day for the first postoperative week. Patients reported the factors that influenced their choice of surgery. RESULTS: There was no difference in baseline function or disease severity between the two groups with regard to QuickDASH and the Boston Carpal Tunnel Questionnaire. Patients in both groups improved after carpal tunnel release with no difference between groups either at postoperative visit 1 for QuickDASH (p = 0.97) and the Boston Carpal Tunnel Questionnaire (p = 0.86) or at postoperative visit 2 for QuickDASH (p = 0.43) and the Boston Carpal Tunnel Questionnaire (p = 0.34). Patients undergoing bilateral carpal tunnel release had more difficulty only during postoperative days 1 to 2 in opening jars (p = 0.03), cooking (p = 0.008), and doing household chores (p = 0.02). Patients in the two groups did not differ (p > 0.05) in their abilities to perform activities of daily living necessary for personal hygiene or independence on any day during the first seven days following surgery with regard to using the bathroom, bathing, dressing, or eating. Although the most common reason why patients chose bilateral carpal tunnel release was to avoid two surgical procedures (42%), the most common reason why patients chose unilateral carpal tunnel release was concern for self-care (36%). CONCLUSIONS: Patients with bilateral carpal tunnel syndrome can anticipate more severe functional impairment during the first few postoperative days with bilateral carpal tunnel release compared with unilateral carpal tunnel release, but limitations beyond postoperative day 2 or 3 are similar for bilateral and unilateral carpal tunnel release. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence

Outer Van Allen belt trapped and precipitating electron flux responses to two interplanetary magnetic clouds of opposite polarity

Recently, it has been established that interplanetary coronal mass ejections (ICMEs) can dramatically affect both trapped electron fluxes in the outer radiation belt and precipitating electron fluxes lost from the belt into the atmosphere. Precipitating electron fluxes and energies can vary over a range of timescales during these events. These variations depend on the initial energy and location of the electron population and the ICME characteristics and structures. One important factor controlling electron dynamics is the magnetic field orientation within the ejecta that is an integral part of the ICME. In this study, we examine Van Allen Probes (RBSPs) and Polar Orbiting Environmental Satellites (POESs) data to explore trapped and precipitating electron fluxes during two ICMEs. The ejecta in the selected ICMEs have magnetic cloud characteristics that exhibit the opposite sense of the rotation of the north-south magnetic field component (B-Z). RBSP data are used to study trapped electron fluxes in situ, while POES data are used for electron fluxes precipitating into the upper atmosphere. The trapped and precipitating electron fluxes are qualitatively analysed to understand their variation in relation to each other and to the magnetic cloud rotation during these events. Inner magnetospheric wave activity was also estimated using RBSP and Geostationary Operational Environmental Satellite (GOES) data. In each event, the largest changes in the location and magnitude of both the trapped and precipitating electron fluxes occurred during the southward portion of the magnetic cloud. Significant changes also occurred during the end of the sheath and at the sheath-ejecta boundary for the cloud with south to north magnetic field rotation, while the ICME with north to south rotation had significant changes at the end boundary of the cloud. The sense of rotation of B-Z and its profile also clearly affects the coherence of the trapped and/or precipitating flux changes, timing of variations with respect to the ICME structures, and flux magnitude of different electron populations. The differing electron responses could therefore imply partly different dominant acceleration mechanisms acting on the outer radiation belt electron populations as a result of opposite magnetic cloud rotation.Peer reviewe

Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment

An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n = 16) or alendronate-pretreated (ALN, n = 29) at teriparatide initiation. Teriparatide (20 μg/day) was given for 24 months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24 months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P = 0.039) and 55 (139)% (P < 0.005) and trabecular thickness 30.4 (30)% (P < 0.001) and 30.8 (53)% (P < 0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r = 0.502 (P < 0.01) and r = 0.378 (P < 0.05), trabecular number, r = 0.559 (P < 0.01) and r = 0.515 (P < 0.01), and reduction of trabecular separation, r = −0.432 (P < 0.05) and r = −0.530 (P < 0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy irrespective of prior antiresorptive use

Lorentz-Abraham-Dirac vs Landau-Lifshitz radiation friction force in the ultrarelativistic electron interaction with electromagnetic wave (exact solutions)

When the parameters of electron - extreme power laser interaction enter the regime of dominated radiation reaction, the electron dynamics changes qualitatively. The adequate theoretical description of this regime becomes crutially important with the use of the radiation friction force either in the Lorentz-Abraham-Dirac form, which possess unphysical runaway solutions, or in the Landau-Lifshitz form, which is a perturbation valid for relatively low electromagnetic wave amplitude. The goal of the present paper is to find the limits of the Landau-Lifshitz radiation force applicability in terms of the electromagnetic wave amplitude and frequency. For this a class of the exact solutions to the nonlinear problems of charged particle motion in the time-varying electromagnetic field is used.Comment: 14 pages, 5 figure

A Statistical Inference Method for Interpreting the CLASP Observations

On 3rd September 2015, the Chromospheric Lyman-Alpha SpectroPolarimeter (CLASP) successfully measured the linear polarization produced by scattering processes in the hydrogen Lyman-$\alpha$ line of the solar disk radiation, revealing conspicuous spatial variations in the $Q/I$ and $U/I$ signals. Via the Hanle effect the line-center $Q/I$ and $U/I$ amplitudes encode information on the magnetic field of the chromosphere-corona transition region (TR), but they are also sensitive to the three-dimensional structure of this corrugated interface region. With the help of a simple line formation model, here we propose a statistical inference method for interpreting the Lyman-$\alpha$ line-center polarization observed by CLASP.Comment: Accepted for publication in The Astrophysical Journa