Expression of transforming growth factor-beta isoforms and their receptors in chronic tendinosis

Chronic tendon lesions are degenerative conditions and may represent a failure to repair or remodel the extracellular matrix after repeated micro-injury. Since TGF-ß is strongly associated with tissue repair, we investigated the expression of TGF-ß isoforms (ß1, ß2 and ß3) and their 2 signalling receptors (TGF-ßRI and TGF-ßRII) in normal and pathological Achilles tendons. In all tissues, all 3 TGF-ß isoforms and the 2 receptors were present at sites of blood vessels. Cells in the matrix showed no staining for TGF-ß1 or ß3, while TGF-ß2 was associated with cells throughout the normal cadaver tendon. Tissue from tendons with pathological lesions showed an increase in cell numbers and percentage TGF-ß2 expression. TGF-ßRII showed a wide distribution in cells throughout the tissue sections. As with TGF-ß2, there was an increase in the number of cells expressing TGF-ßRII in pathological tissue. TGF-ßRI was restricted to blood vessels and was absent from the fibrillar matrix. We conclude that despite the presence and upregulation of TGF-ß2, TGF-ß signalling is not propagated due to the lack of TGF-ßRI. This might explain why chronic tendon lesions fail to resolve and suggests that the addition of exogenous TGF-ß will have little effect on chronic tendinopathy

Exploring Decisions to Undertake a Marathon and Adherence Challenges in a Novice Runner With Parkinson

Evidence endorses the benefits of more vigorous exercise for people with Parkinson’s, particularly following diagnosis, yet is not clear which style is optimal. The authors share perspectives and decisions made as a physiotherapist (assisted by a sports and exercise science student) and a novice runner with Parkinson’s in his late 50s, respectively. The exercise goal chosen by the runner (the case report participant) to minimize the degenerative effects of the progressive condition was to complete a marathon. Methods: This coauthored report evaluates the participant’s progress utilizing physical fitness assessment data plus reflections on his training regime and notes from training diaries for the year before and after the marathon. Results: The participant received nutritional advice for weight management as exercise increased and physiotherapy for injuries from mounting activity level on Parkinsonian muscle tone. Fitness and function improved or were maintained (leg power, flexibility, timed functional walking, and balance). Most, however, returned to baseline within 6 months following the marathon as training intensity dropped. Conclusions: Physical function can be improved or maintained in individuals with neurodegenerative conditions with correct exercise and nutritional advice. The participant’s choice of running was based on recommendations for condition maintenance and not enjoyment, so adherence and completion of the marathon goal required professional, family, and technological support

Coupling of kinesin ATP turnover to translocation and microtubule regulation: one engine, many machines

The cycle of ATP turnover is integral to the action of motor proteins. Here we discuss how variation in this cycle leads to variation of function observed amongst members of the kinesin superfamily of microtubule associated motor proteins. Variation in the ATP turnover cycle among superfamily members can tune the characteristic kinesin motor to one of the range of microtubule-based functions performed by kinesins. The speed at which ATP is hydrolysed affects the speed of translocation. The ratio of rate constants of ATP turnover in relation to association and dissociation from the microtubule influence the processivity of translocation. Variation in the rate-limiting step of the cycle can reverse the way in which the motor domain interacts with the microtubule producing non-motile kinesins. Because the ATP turnover cycle is not fully understood for the majority of kinesins, much work remains to show how the kinesin engine functions in such a wide variety of molecular machines

Physical activity and risk of cancer in middle-aged men

A prospective study was carried out to examine the relationship between physical activity and incidence of cancers in 7588 men aged 40–59 years with full data on physical activity and without cancer at screening. Physical activity at screening was classified as none/occasional, light, moderate, moderately-vigorous or vigorous. Cancer incidence data were obtained from death certificates, the national Cancer Registration Scheme and self-reporting on follow-up questionnaires of doctor-diagnosed cancer. Cancer (excluding skin cancers) developed in 969 men during mean follow-up of 18.8 years. After adjustment for age, smoking, body mass index, alcohol intake and social class, the risk of total cancers was significantly reduced only in men reporting moderately-vigorous or vigorous activity; no benefit seen at lesser levels. Sporting activity was essential to achieve significant benefit and was associated with a significant dose-response reduction in risk of prostate cancer and upper digestive and stomach cancer. Sporting (vigorous) activity was associated with a significant increase in bladder cancer. No association was seen with colo-rectal cancer. Non-sporting recreational activity showed no association with cancer. Physical activity in middle-aged men is associated with reduced risk of total cancers, prostate cancer, upper digestive and stomach cancer. Moderately-vigorous or vigorous levels involving sporting activities are required to achieve such benefit.   http://www.bjcancer.com © 2001 Cancer Research Campaig

Functional Studies on the IBD Susceptibility Gene IL23R Implicate Reduced Receptor Function in the Protective Genetic Variant R381Q

Genome-wide association studies (GWAS) in several populations have demonstrated significant association of the IL23R gene with IBD (Crohn's disease (CD) and ulcerative colitis (UC)) and psoriasis, suggesting that perturbation of the IL-23 signaling pathway is relevant to the pathophysiology of these diseases. One particular variant, R381Q (rs11209026), confers strong protection against development of CD. We investigated the effects of this variant in primary T cells from healthy donors carrying IL23RR381 and IL23RQ381 haplotypes. Using a proprietary anti-IL23R antibody, ELISA, flow cytometry, phosphoflow and real-time RT-PCR methods, we examined IL23R expression and STAT3 phosphorylation and activation in response to IL-23. IL23RQ381 was associated with reduced STAT3 phosphorylation upon stimulation with IL-23 and decreased number of IL-23 responsive T-cells. We also observed slightly reduced levels of proinflammatory cytokine secretion in IL23RQ381 positive donors. Our study shows conclusively that IL23RQ381 is a loss-of-function allele, further strengthening the implication from GWAS results that the IL-23 pathway is pathogenic in human disease. This data provides an explanation for the protective role of R381Q in CD and may lead to the development of improved therapeutics for autoimmune disorders like CD

Stripping the Boss : The Powerful Role of Humor in the Egyptian Revolution 2011

The Egyptian Revolution 2011 has shaken the Arab world and stirred up Middle-East politics. Moreover, it caused a rush in political science and the neighboring disciplines, which had not predicted an event like this and now have troubles explaining it. While many things can be learned from the popular uprising, and from the limitations of previous scholarship, our focus will be on a moral resource, which has occasionally been noticed, but not sufficiently explored: the role of humor in keeping up the spirit of the Revolution. For eighteen days, protestors persevered at Liberation Square in Central Cairo, the epicenter of resistance; at times a few dozens, at times hundreds of thousands. What they did was to fight the terror of the regime, which reached absurd peaks during those days, with humor – successfully. We offer a social-functionalist account of the uprising, which includes behavioral as well as cultural levels of analysis, and illuminates how humorous means helped to achieve deadly serious goals. By reconstructing how Egyptians laughed themselves into democracy, we outline a social psychology of resistance, which uses humor both as a sword and a shield.Peer reviewe

A review on the progress and challenges of binder jet 3D printing of sand moulds for advanced casting

3D sand mould printing through binder jetting can solve many technical issues in casting including part consolidation, design of parts to optimise the consumption of materials and hazardous chemicals, and on-demand and any size part manufacturing near the customer. Incorporating artificial intelligence in optimising the design of moulds, printing process parameters, and solidification processes may help automate a production facility and reduce labour time. Elimination of hazardous chemicals from industrial use may be a challenge. Therefore, an alternative technology to fuse the sand particles during printing or an environmentally friendlier alternative option for the binders and other consumables should be utilised with the 3D sand printing process. Properties of parts produced using 3D printed sand moulds are better than the properties of parts produced using traditional casting due to this technology's benefits mentioned above. Though this technology is a supportive enabling technology for the traditional casting processes rather than a competing technology. This technology is causing a paradigm shift in casting design because of the mould geometries achievable using the sand moulds' additive manufacturing. This paper reviews the first twenty years of research and challenges in developing 3D sand printing as an innovation for sustainable manufacturing