Single molecule MATAC-seq reveals key determinants of DNA replication origin efficiency

Stochastic origin activation gives rise to significant cell-to-cell variability in the pattern of genome replication. The molecular basis for heterogeneity in efficiency and timing of individual origins is a long-standing question. Here, we developed Methylation Accessibility of TArgeted Chromatin domain Sequencing (MATAC-Seq) to determine single-molecule chromatin accessibility of four specific genomic loci. MATAC-Seq relies on preferential modification of accessible DNA by methyltransferases combined with Nanopore-Sequencing for direct readout of methylated DNA-bases. Applying MATAC-Seq to selected early-efficient and late-inefficient yeast replication origins revealed large heterogeneity of chromatin states. Disruption of INO80 or ISW2 chromatin remodeling complexes leads to changes at individual nucleosomal positions that correlate with changes in their replication efficiency. We found a chromatin state with an accessible nucleosome-free region in combination with well-positioned +1 and +2 nucleosomes as a strong predictor for efficient origin activation. Thus, MATAC-Seq identifies the large spectrum of alternative chromatin states that co-exist on a given locus previously masked in population-based experiments and provides a mechanistic basis for origin activation heterogeneity during eukaryotic DNA replication. Consequently, our single-molecule chromatin accessibility assay will be ideal to define single-molecule heterogeneity across many fundamental biological processes such as transcription, replication, or DNA repair in vitro and ex vivo

A three month controlled intervention of intermittent whole body vibration designed to improve functional ability and attenuate bone loss in patients with rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune condition that results in pain and disability. Patients with RA have a decreased functional ability and are forced into a sedentary lifestyle and as such, these patients often become predisposed to poor bone health. Patients with RA may also experience a decreased health related quality of life (HRQoL) due to their disease. Whole body vibration (WBV) is a form of exercise that stimulates bone loading through forced oscillation. WBV has also been shown to decrease pain and fatigue in other rheumatic diseases, as well as to increase muscle strength. This paper reports on the development of a semi randomised controlled clinical trial to assess the impact of a WBV intervention aiming to improve functional ability, attenuate bone loss, and improve habitual physical activity levels in patients with RA. Methods/Design: This study is a semi randomised, controlled trial consisting of a cohort of patients with established RA assigned to either a WBV group or a CON (control) group. Patients in the WBV group will undergo three months of twice weekly intermittent WBV sessions, while the CON group will receive standard care and continue with normal daily activities. All patients will be assessed at baseline, following the three month intervention, and six months post intervention. Main outcomes will be an improvement in functional ability as assessed by the HAQ. Secondary outcomes are attenuation of loss of bone mineral density (BMD) at the hip and changes in RA disease activity, HRQoL, habitual physical activity levels and body composition. Discussion: This study will provide important information regarding the effects of WBV on functional ability and BMD in patients with RA, as well as novel data regarding the potential changes in objective habitual physical activity patterns that may occur following the intervention. The sustainability of the intervention will also be assessed

A mission control architecture for robotic lunar sample return as field tested in an analogue deployment to the Sudbury impact structure

A Mission Control Architecture is presented for a Robotic Lunar Sample Return Mission which builds upon the experience of the landed missions of the NASA Mars Exploration Program. This architecture consists of four separate processes working in parallel at Mission Control and achieving buy-in for plans sequentially instead of simultaneously from all members of the team. These four processes were: Science Processing, Science Interpretation, Planning and Mission Evaluation. Science Processing was responsible for creating products from data downlinked from the field and is organized by instrument. Science Interpretation was responsible for determining whether or not science goals are being met and what measurements need to be taken to satisfy these goals. The Planning process, responsible for scheduling and sequencing observations, and the Evaluation process that fostered inter-process communications, reporting and documentation assisted these processes. This organization is advantageous for its flexibility as shown by the ability of the structure to produce plans for the rover every two hours, for the rapidity with which Mission Control team members may be trained and for the relatively small size of each individual team. This architecture was tested in an analogue mission to the Sudbury impact structure from June 6-17, 2011. A rover was used which was capable of developing a network of locations that could be revisited using a teach and repeat method. This allowed the science team to process several different outcrops in parallel, downselecting at each stage to ensure that the samples selected for caching were the most representative of the site. Over the course of 10 days, 18 rock samples were collected from 5 different outcrops, 182 individual field activities - such as roving or acquiring an image mosaic or other data product - were completed within 43 command cycles, and the rover travelled over 2,200 m. Data transfer from communications passes were filled to 74%. Sample triage was simulated to allow down-selection to 1kg of material for return to Earth

The 8th September: World physical therapy day

Every day physiotherapists around the world strive to provide the best quality of services to their patients. The World Confederation for Physical Therapy (WCPT), which was founded on 8th September 1951, has a goal to promote international health by encouraging the use of research in education and by exchanging opinions and information. For that reason, 8th September has been established as a day which ‘marks the unity and solidarity of the physical therapy community from 101 countries around the world’ (WCPT, 2010) and highlights the contribution of the physiotherapy profession to patient rehabilitation. © 2008, MA Healthcare Ltd. All rights reserved

Whole-body vibration and rehabilitation of chronic diseases: A review of the literature

The objectives of the study were to review the current literature and findings on the effects of whole-body vibration (WBV) as a training method on performance and its ability to aid in the rehabilitation of chronic diseases (neurological, musculoskeletal or metabolic conditions). Six electronic databases were searched. The combination of the search terminology used included WBV and several neurological, musculoskeletal and metabolic conditions. Twenty six papers were found to be relevant for this review and were included for critical evaluation with regards to sample characteristics, research intervention and methodology. Most studies were conducted on patients diagnosed with neurological conditions (n = 15) while less were performed on patients suffering from musculoskeletal (n = 7) or metabolic (n = 4) disorders. Comparisons were difficult to draw on because of the different pathologies and the differences in the methodology of each study. Some of the observed methodological flaws included limitations in relation to insufficient randomisation, lack of sample homogeneity (size, age variability) and poor blinding in most studies. No consensus could be reached as to whether WBV is more effective than other interventions or no intervention at all, while the additional effects that WBV may have in relation to other interventions could not be assumed. Nevertheless, chronic WBV training seems to only improve strength in neurological patients while balance and mobility improves only in patients suffering from musculoskeletal or metabolic but not from neurological conditions. Although WBV did not prove to be more effective compared to other training methods, it can be used, in some cases, as a less fatiguing and less time-consuming method to enhance physical capabilities. Future research should focus on the effectiveness of WBV in relation to no treatment at all, and to age

The acute effects of different whole-body vibration amplitudes and frequencies on flexibility and vertical jumping performance

Frequency and amplitude determine the training load of whole-body vibration (WBV) exercise and thereby possible neuromuscular adaptations. We investigated the effects of amplitude and frequency of a single bout of WBV on flexibility and squat jump performance (SJ) and the time-course of these effects. In the amplitude study, twenty-five females performed three vibration protocols (VPs) for 6 min at frequency of 25 Hz and amplitudes of 4 mm, 6 mm, and 8 mm and one control protocol (CP). In the frequency study, eighteen females performed three VPs at 6 mm amplitude and frequencies of 15 Hz, 20 Hz, and 30Hz and one CP. Flexibility and SJ were measured before, immediately-post and 15 min recovery. All protocols were performed on a side-to-side alternating vibration plate. In the amplitude study, flexibility was improved (p < 0.01) immediately-post in VP4, VP6, VP8 (31.8 +/- 8.2, 31.9 +/- 7.6, 31.5 +/- 7.9, respectively) and at 15 min recovery (31.6 +/- 8.1, 31.5 +/- 7.9, 31.0 +/- 8.2, respectively) vs. pre-vibration (30.2 +/- 8.6, 30.3 +/- 8.1, 30.2 +/- 8.3, respectively), but remained unchanged in CP (30.6 +/- 8.3 immediately-post, 30.7 +/- 8.2 at 15 min vs. 30.4 +/- 8.2 pre-vibration). In the frequency study, flexibility was improved (p < 0.01) immediately-post in VP15, VP20, VP30 (31.5 +/- 5.2, 31.3 +/- 5, 31.7 +/- 5.3, respectively) and at 15 min recovery (31.3 +/- 5.4, 31.3 +/- 5.0, 31.3 +/- 5.3, respectively) vs. pre-vibration (30.6 +/- 5.4, 30.2 +/- 5.7, 30.3 +/- 5.9, respectively), but not in CP (30.7 +/- 5.1 immediately-post, 30.6 +/- 5 at 15 min vs. pre-vibration 30.5 +/- 5.7). There were no significant effects of amplitude or frequency on SJ. In conclusion, a single WBV bout using a side-to-side alternating vibration plate may increase flexibility which persists for at least 15 min, without altering jumping performance. These effects were observed irrespective of frequency and amplitude. (C) 2009 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved