Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke

Morphological Transformations of Galaxies in the A901/02 Supercluster from STAGES

We present a study of galaxies in the Abell 901/902 Supercluster at z~0.165, based on HST ACS F606W, COMBO-17, Spitzer 24um, XMM-Newton X-ray, and gravitational lensing maps, as part of the STAGES survey. We characterize galaxies with strong externally-triggered morphological distortions and normal relatively undisturbed galaxies, using visual classification and quantitative CAS parameters. We compare normal and distorted galaxies in terms of their frequency, distribution within the cluster, star formation properties, and relationship to dark matter (DM) or surface mass density, and intra-cluster medium (ICM) density. We revisit the morphology density relation, which postulates a higher fraction of early type galaxies in dense environments, by considering separately galaxies with a low bulge-to-disk (B/D) ratio and a low gas content as these two parameters may not be correlated in clusters. We report here on our preliminary analysis.Comment: To appear in the ASP conference proceedings of the "Frank N. Bash Symposium 2007: New Horizons in Astronomy", Eds. A. Frebel, J. Maund, J. Shen, M. Siegel. 4 pages, 4 figure

Physiological Effects of Tapering and Detraining in World-Class Kayakers

. Purpose: This study analyzed changes in neuromuscular, body composition, and endurance markers during 4 wk of tapering and subsequent 5 wk of reduced training (RT) or training cessation (TC). Methods: Fourteen world-class kayakers were randomly assigned to either a TC (n = 7) or an RT group (n = 7). One-repetition maximum (1RM) strength, mean concentric velocity with 45% 1RM (V 45% ) in the bench press (BP) and prone bench pull (PBP) exercises, and body composition assessments were conducted at the start (T0) and end (T1) of a 43-wk training program, after tapering for the world championships (T2) and after TC or RT (T3). A graded exercise test on a kayak ergometer for determination of maximal oxygen uptake at T0, T1, and T3 was also performed. Results: After tapering, no significant changes were observed in 1RM or V 45% . TC resulted in significantly greater declines in 1RM strength (j8.9% and j7.8%, P G 0.05, respectively, for BP and PBP) than those observed for RT (j3.9% and j3.4%). Decreases in V 45% in BP and PBP were larger for TC (j12.6% and j10.0%) than for RT (j9.0% and j6.7%). Increases in sum of eight skinfolds were observed after both TC and RT, whereas declines in maximal aerobic power were lower for RT (j5.6%) than for TC (j11.3%). Conclusions: Short-term TC results in large decreases in maximal strength and especially V 45% in highly trained athletes. These results suggest the need of performing a minimal maintenance program to avoid excessive declines in neuromuscular function in cases where a prolonged break from training is required. Key Words: TRAINING CESSATION, REDUCED TRAINING, MAXIMAL STRENGTH, MUSCLE POWER, CANOEING A well-known and proven effective coaching strategy for improving sports performance before main competition events is to incorporate a tapering phase of significantly reduced training (RT) volume while the intensity is kept high The incorporation of periods of 3-6 wk of training cessation (TC) after the conclusion of the main event of the season to allow physical and mental recovery before the start of a new training cycle is a common training practice in many sports. In these situations, training reduction is generally preferred over complete exercise stoppage because it seems to be more effective to avoid the negative impact of insufficient training stimuli on athletic performance (21). The magnitude of performance declines observed after detraining periods appears to be related to the chosen recovery strategy (i.e., reduced training (RT) or complete training cessation (TC)), initial fitness level, and total time under reduced or absence of training stimuli Current research seems to indicate that neuromuscular performance is more susceptible to decline because of detraining in highly trained athletes compared with recently or moderately trained individual

Master equations for effective Hamiltonians

We reelaborate on a general method for obtaining effective Hamiltonians that describe different nonlinear optical processes. The method exploits the existence of a nonlinear deformation of the su(2) algebra that arises as the dynamical symmetry of the original model. When some physical parameter (usually related to the dispersive limit) becomes small, we immediately get a diagonal effective Hamiltonian that represents correctly the dynamics for arbitrary states and long times. We apply the same technique to obtain how the noise terms in the original model transform under this scheme, providing a systematic way of including damping effects in processes described in terms of effective Hamiltonians.Comment: 10 pages, no figure

Phi-values in protein folding kinetics have energetic and structural components

Phi-values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Phi-values measure energetic quantities, but are often interpreted in terms of the structures of the transition state ensemble. Here we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Phi-values have both structural and energetic components. In addition, it provides a natural and general interpretation of "nonclassical" Phi-values (i.e., less than zero, or greater than one). The model reproduces the Phi-values for 20 single-residue mutations in the alpha-helix of the protein CI2, including several nonclassical Phi-values, in good agreement with experiments.Comment: 15 pages, 3 figures, 1 tabl

Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-? are targets of the autoimmune response in type 1 diabetes

Type 1 diabetes (T1D) results from the destruction of pancreatic beta-cells by the immune system, and CD8(+) T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-beta. Previous work has shown increased proliferative responses to whole S100-beta in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen-A*02:01 (A2.1) molecules derived from S100-beta. These NPPEs triggered IFN-gamma responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-beta-specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.-Calvino-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gomez-Perosanz, M., Sanchez-Trincado, J. L., Rodriguez, M. A., Sueiro, A. M., Vinuela, J. E., Calvino, R. V. Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-beta are targets of the autoimmune response in type 1 diabetes

Health Outcome Predictive Evaluation for COVID 19 international registry (HOPE COVID-19), rationale and design

The disease produced by the new coronavirus known as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), named COVID-19 (Coronavirus Disease-2019) has recently been classified as a pandemic by the World Health Organization (WHO). However, scarce clinical data is available and generally limited to the Chinese population due to the first cases were identified in Wuhan (Hubei, China).This article describes the rationale and design of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) registry (ClinicalTrials.gov Identifier: NCT04334291). With an ambispective cohort design, eligible patients are those discharged, deceased or alive, from any hospital center with a confirmed diagnosis or a COVID-19 high suspicion. With a current recruitment of more than 7000 cases, in 46 hospitals in 8 countries, since it is not possible to estimate the sample size based on literature reports, the investigators will try to get the maximum numbers of patients possible. The study primary objective is all cause mortality and aims to characterize the clinical profile of patients infected in order to develop a prognostic clinical score allowing, rapid logistic decision making. As secondary objectives, the analysis of other clinical events, the risk-adjusted influence of treatments and previous comorbidities of patients infected with the disease will be performed.The results of HOPE COVID-19 will contribute to a better understanding of this condition. We aim to describe the management of this condition as well as the outcomes in relation to the therapy chosen, in order to gain insight into improving patient care in the coming months. Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT04334291