MTMDAT: Automated analysis and visualization of mass spectrometry data for tertiary and quaternary structure probing of proteins

Summary: In structural biology and -genomics, nuclear magnetic resonance (NMR) spectroscopy and crystallography are the methods of choice, but sample requirements can be hard to fulfil. Valuable structural information can also be obtained by using a combination of limited proteolysis and mass spectrometry, providing not only knowledge of how to improve sample conditions for crystallization trials or NMR spectrosopy by gaining insight into subdomain identities but also probing tertiary and quaternary structure, folding and stability, ligand binding, protein interactions and the location of post-translational modifications. For high-throughput studies and larger proteins, however, this experimentally fast and easy approach produces considerable amounts of data, which until now has made the evaluation exceedingly laborious if at all manually possible. MTMDAT, equipped with a browser-like graphical user interface, accelerates this evaluation manifold by automated peak picking, assignment, data processing and visualization

CAN REHABILITATION IN THE HOME SETTING REDUCE THE BURDEN OF CARE FOR THE NEXT-OF-KIN OF STROKE VICTIMS? 1

Can rehabilitation in the home setting reduce the burden of care for the next-of-kin of stroke victims?. Background: More evidence of the efficacy of caregiver interventions is needed. The aim of this study was to evaluate whether counselling in the home setting reduces the care giver burden. Methods: Thirtysix patients after stroke, median age 53 years, with a close family member, were selected for an evaluation of the burden of care and 35 participated. They were part of a randomized controlled trial, comparing rehabilitation in the home setting with outpatient rehabili tation. In the home setting, counselling about the stroke and its consequences was included. Assessments with the Care giver Burden scale were made at 3 weeks, 3 months and one year after discharge. Results: The burden of the 2 groups did not differ. After the intervention, there was a tendency to a lower burden for the home setting. The burden for the home setting was then unchanged from 3 weeks to 1 year, while outpatient rehabilitation showed a reduced burden over time. For the home setting, significant correlations to activity level were seen after the intervention. Conclusion: A positive effect of counselling was seen, as the home setting burden tends to be lower after the intervention, while outpatient rehabilitation seems to adjust with time. The results suggest that counselling reduces burden and the remaining burden is associated with the patient's ability. Journal of Rehabilitation Medicin

Early prediction of upper limb functioning after stroke using clinical bedside assessments: a prospective longitudinal study.

Early and accurate prediction of recovery is needed to assist treatment planning and inform patient selection in clinical trials. This study aimed to develop a prediction algorithm using a set of simple early clinical bedside measures to predict upper limb capacity at 3-months post-stroke. A secondary analysis of Stroke Arm Longitudinal Study at Gothenburg University (SALGOT) included 94 adults (mean age 68 years) with upper limb impairment admitted to stroke unit). Cluster analysis was used to define the endpoint outcome strata according to the 3-months Action Research Arm Test (ARAT) scores. Modelling was carried out in a training (70%) and testing set (30%) using traditional logistic regression, random forest models. The final algorithm included 3 simple bedside tests performed 3-days post stroke: ability to grasp, to produce any measurable grip strength and abduct/elevate shoulder. An 86-94% model sensitivity, specificity and accuracy was reached for differentiation between poor, limited and good outcome. Additional measurement of grip strength at 4 weeks post-stroke and haemorrhagic stroke explained the underestimated classifications. External validation of the model is recommended. Simple bedside assessments have advantages over more lengthy and complex assessments and could thereby be integrated into routine clinical practice to aid therapy decisions, guide patient selection in clinical trials and used in data registries

Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block

Congenital heart block develops in fetuses after placental transfer of Ro/SSA autoantibodies from rheumatic mothers. The condition is often fatal and the majority of live-born children require a pacemaker at an early age. The specific antibody that induces the heart block and the mechanism by which it mediates the pathogenic effect have not been elucidated. In this study, we define the cellular mechanism leading to the disease and show that maternal autoantibodies directed to a specific epitope within the leucine zipper amino acid sequence 200–239 (p200) of the Ro52 protein correlate with prolongation of fetal atrioventricular (AV) time and heart block. This finding was further confirmed experimentally in that pups born to rats immunized with p200 peptide developed AV block. p200-specific autoantibodies cloned from patients bound cultured cardiomyocytes and severely affected Ca2+ oscillations, leading to accumulating levels and overload of intracellular Ca2+ levels with subsequent loss of contractility and ultimately apoptosis. These findings suggest that passive transfer of maternal p200 autoantibodies causes congenital heart block by dysregulating Ca2+ homeostasis and inducing death in affected cells

A multicenter study on transfer, walking and stair climbing in persons with stroke admitted to specialized rehabilitation

Background: Walking on even surface and stair walking capacity are prerequisites for independence, and these capacities are often referred to as primary goals in rehabilitation after stroke

Specialized stroke rehabilitation services in seven countries

Background There is a lack of defined levels of rehabilitation, indicating possibly random content and access to specialized services. Aims and/or hypothesis The aim of the study was to perform a multinational descriptive study of specialized rehabilitation in persons with stroke, to elucidate what the different centers define as prerequisites for specialized rehabilitation, and to analyze whether these descriptions map to currently applied standards or constructs of specialized rehabilitation. A secondary aim was to look for similarities and differences between therapies and services for persons with stroke in the sub-acute stage in the different institutions. Methods Descriptive data of the collaborating centers regarding structure and processes of services were recorded and compared with the British Society of Rehabilitation Medicine and Specialized Services National Definitions sets. Results Comparisons of the definitions

White book on physical and rehabilitation medicine (PRM) in Europe. Chapter 10. Science and research in PRM: Specificities and challenges

In the context of the White Book of Physical and Rehabilitation Medicine (PRM), this paper deals with Research, the future of PRM. PRM students and specialists are mainly involved in biomedical research, investigating the biological processes, the causes of diseases, their medical diagnosis, the evaluation of their consequences on functioning, disability and health and the effects of health interventions at an individual and a societal level. Most of the current PRM research, often interdisciplinary, originates from applied research which, using existing knowledge, is directed towards specific goals. Translational medical research, research and development, implementation research and clinical impact research are in this field. PRM physicians, mainly master or PhD students, are nowadays increasing their participation in basic research and in pre-clinical trials. PRM physicians are involved in primary research, which is an original first hand research, but also in secondary research, which is the analysis and interpretation of primary research publications in a field, with a specific methodology. Secondary research remains an important activity of the UEMS PRM section and it will be the field of the new created Cochrane Rehabilitation. Secondary research with interest for persons with disabilities, will be developed world wide on the basis of evidence based medicine, with the participation of PRM physicians and of all other health and social professionals involved in rehabilitation. The development of research activities with interest for PRM in Europe is a challenge for the future, which has to be faced now. The European PRM schools, the European master and PhD program with their supporting research and clinical facilities, the European PRM organizations with their websites, the PRM scientific journals and European congresses are a strong basis to develop research activities, together with the development of Cochrane Rehabilitation field and of our cooperation with European high level research facilities, European and international scientific societies in different fields. PRM will be a leader in this field of research

SCF Ensures Meiotic Chromosome Segregation Through a Resolution of Meiotic Recombination Intermediates

The SCF (Skp1-Cul1-F-box) complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB) formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation