The 4U 0115+63: Another energetic gamma ray binary pulsar

Following the discovery of Her X-1 as a source of pulsed 1000 Gev X-rays, a search for emission from an X-ray binary containing a pulsar with similar values of period, period derivative and luminosity was successful. The sporadic X-ray binary 4U 0115-63 has been observed, with probability 2.5 x 10 to the minus 6 power ergs/s to emit 1000 GeV gamma-rays with a time averaged energy flux of 6 to 10 to the 35th power

Pre-menarcheal physical activity predicts post-menarcheal lean mass and core strength, but not fat mass

Abstract Objectives: Youth exercise is associated with improved body composition, but details regarding timing and persistence are limited. We examined pre-and circum-menarcheal organized physical activity exposure (PA) as a factor in development of early post-menarcheal lean mass, fat mass and muscle strength. Methods: Participants in a longitudinal study of musculoskeletal growth using dual energy X-ray absorptiometry (DXA) were included based on: 1) Whole body DXA scans: 0.5-1.5 years pre-menarche, 0.5-1.5 years post-menarche; 2) PA records for ≥6 months preceding the first DXA (prePA) and for the inter-DXA interval (circumPA). Dominant arm grip strength and sit-ups tests coincided with DXA scans; PA, height and maturity were recorded semi-annually. Regressions correlated PA with lean mass/fat mass/strength, accounting for maturity, body size, and baseline values. Results: Seventy girls [baseline: 11.8 yrs (sd 1.0), follow-up: 13.9 years (sd 1.0)] demonstrated circum-menarcheal gains of 25-29% for lean and fat mass and 33% for grip strength. prePA correlated with pre-and post-menarcheal lean mass, sit-ups and pre-menarcheal fat mass (p<0.05), but not grip strength. circumPA correlated with only post-menarcheal sub-head lean mass (p=0.03). Conclusions: Lean mass and core strength at 1-year post-menarche were more strongly predicted by pre-menarcheal organized PA than by recent circum-menarcheal PA

Arm bone loading index predicts DXA musculoskeletal outcomes in two samples of post-menarcheal girls

Abstract Objective: A site-specific bone loading index was developed to predict post-menarcheal arm bone mass, geometry, areal density and non-bone lean mass using organized activity records. Methods: Two cohorts of post-menarcheal girls (A= 55, B= 48) met analysis inclusion criteria: 1) Whole body and non-dominant radius DXA scans +1.0 to +2.6 years post-menarche; 2) detailed, organized activity records available for 36 months prior to the focal DXA scan; 3) accompanying anthropometric data. DXA non-dominant arm and radius regions of interest (1/3, Ultradistal (UD)) were evaluated. An arm bone loading index (arm totBLI) was developed and refined to describe >50 activities. Separate regression analyses for Cohorts A&B tested explanatory value of arm totBLI for DXA outcomes, accounting for gynecological age, height and whole body non-bone lean mass. Results: In both cohorts, arm totBLI reflecting 3 years of peri-menarcheal activity exposure exhibited strong explanatory value for post-menarcheal radius and arm outcomes (squared semi-partial r =0.07-0.34, p<0.05), except Arm Area. For both cohorts and most outcomes, arm totBLI explained significant variance, even after adjusting for local muscle mass. Conclusions: In two independent cohorts, arm totBLI may consistently indicate osteogenic and sarcogenic properties of represented activities; additional research is necessary for further refinement and validation

Mechanical Influences on Morphogenesis of the Knee Joint Revealed through Morphological, Molecular and Computational Analysis of Immobilised Embryos

Very little is known about the regulation of morphogenesis in synovial joints. Mechanical forces generated from muscle contractions are required for normal development of several aspects of normal skeletogenesis. Here we show that biophysical stimuli generated by muscle contractions impact multiple events during chick knee joint morphogenesis influencing differential growth of the skeletal rudiment epiphyses and patterning of the emerging tissues in the joint interzone. Immobilisation of chick embryos was achieved through treatment with the neuromuscular blocking agent Decamethonium Bromide. The effects on development of the knee joint were examined using a combination of computational modelling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations, cell proliferation assays and in situ hybridisation to examine the expression of a selected panel of genes known to regulate joint development. This work revealed the precise changes to shape, particularly in the distal femur, that occur in an altered mechanical environment, corresponding to predicted changes in the spatial and dynamic patterns of mechanical stimuli and region specific changes in cell proliferation rates. In addition, we show altered patterning of the emerging tissues of the joint interzone with the loss of clearly defined and organised cell territories revealed by loss of characteristic interzone gene expression and abnormal expression of cartilage markers. This work shows that local dynamic patterns of biophysical stimuli generated from muscle contractions in the embryo act as a source of positional information guiding patterning and morphogenesis of the developing knee joint

Basement membrane components are key players in specialized extracellular matrices

More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches

Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue engineering

Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites

The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

The Potential of microRNAs for Stem Cell-based Therapy for Degenerative Skeletal Diseases

Purpose of review: degenerative skeletal disorders including osteoarthritis (OA) and osteoporosis (OP) are the result of attenuation of tissue regeneration and lead to painful conditions with limited treatment options. Preventative measures to limit the onset of OA and OP remain a significant unmet clinical need. MicroRNAs (miRNAs) are known to be involved in the differentiation of stem cells, and in combination with stem cell therapy could induce skeletal regeneration and potentially prevent OA and OP onset.Recent findings: the combination of stem cells and miRNA has been successful at regenerating the bone and cartilage in vivo. MiRNAs, including miR-146b known to be involved in chondrogenic differentiation, could provide innovative targets for stem cell-based therapy, for the repair of articular cartilage defects forestalling the onset of OA or in the generation of a stem cell-based therapy for OP.Summary: this review discusses the combination of skeletal stem cells (SSCs) and candidate miRNAs for application in a cell-based therapy approach for skeletal regenerative medicine