Tendons: structure, function and challenges to clinical treatment

As dense connective tissues, tendons play a vital role in the transmission of contractile forces from muscle to bone. This link between muscles and bones provides the means in transferring tensile forces produced by muscles on to the connected bone. During movement, tendons slide over surrounding bony and articular surfaces and are thus commonly subjected to shear and compression forces in addition to tensile force. Fibrillar collagen, proteoglycan and various glycoproteins make up the composition of tendinous tissue and contribute to its ability to withstand these forces. Tendons contain a distinct population of cells, called tenocytes. Tenocytes undertake a flattened morphology within the tendon matrix and contain cytoplasmic projections which extend longitudinally and laterally towards other tenocytes. An intercellular network of cells thus maintains the extracellular environment of the tendon and allows a coordinated response to external mechanical stimuli. Defects to load-bearing connective tissue elements such as tendons whether due to trauma, overuse, age-related diseases or degenerative diseases, are often limited in their healing potential and thus contributes often to persistent, chronic clinical symptoms. Chronic disease, overuse or acute injuries damages the tendon. This damage compromises the transmission of tensile forces and because of the hypovascularity of some tendinous tissues and many other reasons, a healing response often is severely insufficient in regenerating tissue back to its original constitution. Even the best treatment options for such tendinopathies, supplemented with the body’s own healing response fail to produce quality outcomes. An understanding of the molecular, cellular and mechanical characteristics of tenocytes, tendon matrix and the tendon system as a whole will be vital for the development of effective therapies for all tendinopathies. It is the goal of this current work to outline the current molecular, cellular, mechanical and clinical understanding of tendons. A broad address to tendon biology should help illustrate the key dimensional aspects that must be considered when attempting the effective translation of research into useful clinical therapies

Tendons: structure, function and challenges to clinical treatment

As dense connective tissues, tendons play a vital role in the transmission of contractile forces from muscle to bone. This link between muscles and bones provides the means in transferring tensile forces produced by muscles on to the connected bone. During movement, tendons slide over surrounding bony and articular surfaces and are thus commonly subjected to shear and compression forces in addition to tensile force. Fibrillar collagen, proteoglycan and various glycoproteins make up the composition of tendinous tissue and contribute to its ability to withstand these forces. Tendons contain a distinct population of cells, called tenocytes. Tenocytes undertake a flattened morphology within the tendon matrix and contain cytoplasmic projections which extend longitudinally and laterally towards other tenocytes. An intercellular network of cells thus maintains the extracellular environment of the tendon and allows a coordinated response to external mechanical stimuli. Defects to load-bearing connective tissue elements such as tendons whether due to trauma, overuse, age-related diseases or degenerative diseases, are often limited in their healing potential and thus contributes often to persistent, chronic clinical symptoms. Chronic disease, overuse or acute injuries damages the tendon. This damage compromises the transmission of tensile forces and because of the hypovascularity of some tendinous tissues and many other reasons, a healing response often is severely insufficient in regenerating tissue back to its original constitution. Even the best treatment options for such tendinopathies, supplemented with the body’s own healing response fail to produce quality outcomes. An understanding of the molecular, cellular and mechanical characteristics of tenocytes, tendon matrix and the tendon system as a whole will be vital for the development of effective therapies for all tendinopathies. It is the goal of this current work to outline the current molecular, cellular, mechanical and clinical understanding of tendons. A broad address to tendon biology should help illustrate the key dimensional aspects that must be considered when attempting the effective translation of research into useful clinical therapies

Steady Viscous Flow in a Triangular Cavity

Steady recirculating viscous flow inside an equilateral triangular cavity is generated by translating one side. The Navier-Stokes equations are solved numerically using finite difference on a transformed geometry. The results show a primary eddy and a series of secondary eddies at the stagnant corner. For high Reynolds numbers the interior of the primary eddy has constant vorticity, but its value cannot be predicted by the mean-squared law

Steady Viscous Flow in a Trapezoidal Cavity

The flow in a trapezoidal cavity (including the rectangular and triangular cavities) with one moving wall is studied numerically by finite differences with special treatment in the corners. It is found that streamlines and vorticity distributions are sensitive to geometric changes. The mean square law for core vorticity is valid for the rectangle but ceases to be valid for the triangular cavity

An Efficient System for Heterologous Expression of Secondary Metabolite Genes in Aspergillus nidulans

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ja401945a.Fungal secondary metabolites (SMs) are an important source of medically valuable compounds. Genome projects have revealed that fungi have many SM biosynthetic gene clusters that are not normally expressed. To access these potentially valuable, cryptic clusters, we have developed a heterologous expression system in Aspergillus nidulans. We have developed an efficient system for amplifying genes from a target fungus, placing them under control of a regulatable promoter, transferring them into A. nidulans and expressing them. We have validated this system by expressing non-reducing polyketide synthases of Aspergillus terreus and additional genes required for compound production and release. We have obtained compound production and release from six of these NR-PKSs and have identified the products. To demonstrate that the procedure allows transfer and expression of entire secondary metabolite biosynthetic pathways, we have expressed all the genes of a silent A. terreus cluster and demonstrate that it produces asperfuranone. Further, by expressing the genes of this pathway in various combinations, we have clarified the asperfuranone biosynthetic pathway. We have also developed procedures for deleting entire A. nidulans SM clusters. This allows us to remove clusters that might interfere with analyses of heterologously expressed genes and to eliminate unwanted toxins

Vorticity Induced by a Moving Elliptic Belt

The viscous flow inside an elliptic moving belt is studied using Newton's method on a Hermite collocation approximation. The streamlines and especially the vorticity distribution are found for Reynolds number up to 1000 and aspect ratio up to five. For low Reynolds numbers vorticity diffuses from regions of high curvature. For high Reynolds numbers there exists a closed boundary layer and a core of constant vorticity. The core vorticity compares well with the estimation from the mean square law

Oedema extension distance in intracerebral haemorrhage: Association with baseline characteristics and long-term outcome

Introduction: Oedema extension distance is a derived parameter that may reduce sample size requirements to demonstrate reduction in perihaematomal oedema in early phase acute intracerebral haemorrhage trials. We aimed to identify baseline predictors of oedema extension distance and its association with clinical outcomes. Patients and methods: Using Virtual International Stroke Trials Archive-Intracerebral Haemorrhage, first Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial, and Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation II datasets, we calculated oedema extension distance at baseline and at 72 h measured using computed tomography. Using linear regression, we tested for associations between baseline characteristics and oedema extension distance at 72 h. Ordinal regression (underlying assumptions validated) was used to test for associations between oedema extension distance at baseline and 72 h and oedema extension distance change between baseline and 72 h, and modified Rankin scale scores at 90 days, adjusted for baseline and 72 h prognostic factors. Results: There were 1028 intracerebral haemorrhage cases with outcome data for analyses. Mean (standard deviation, SD) oedema extension distance at 72 h was 0.54 (0.26) cm, and mean oedema extension distance difference from baseline (EED72–0) was 0.24 (0.18) cm. Oedema extension distance at 72 h was greater with increasing baseline haematoma volume and baseline oedema extension distance. Increasing age, lobar haemorrhage, and intraventricular haemorrhage were independently associated with EED72–0. In multifactorial ordinal regression analysis, EED72–0 was associated with worse modified Rankin scale scores at 90 days (odds ratio 1.96, 95% confidence interval 1.00–3.82). Discussion: Increase in oedema extension distance over 72 h is independently associated with decreasing functional outcome at 90 days. Oedema extension distance may be a useful surrogate outcome measure in early phase trials of anti-oedema or anti-inflammatory treatments in intracerebral haemorrhage

Global patterns and drivers of leaf photosynthetic capacity : the relative importance of environmental factors and evolutionary history

Altres ajuts: Fundación Ramon Areces grant CIVP20A6621Aim: understanding the considerable variability and drivers of global leaf photosynthetic capacity [indicated by the maximum carboxylation rate standardized to 25°C (Vc,max25)] is an essential step for accurate modelling of terrestrial plant photosynthesis and carbon uptake under climate change. Although current environmental conditions have often been connected with empirical and theoretical models to explain global Vc,max25 variability through acclimatization and adaptation, long-term evolutionary history has largely been neglected, but might also explicitly play a role in shaping the Vc,max25 variability. - Location: global - Time period: contemporary - Major taxa studied: terrestrial plants. - Methods: we compiled a geographically comprehensive global dataset of Vc,max25 for C3 plants (n = 6917 observations from 2157 species and 425 sites covering all major biomes world-wide), explored the biogeographical and phylogenetic patterns of Vc,max25, and quantified the relative importance of current environmental factors and evolutionary history in driving global Vc,max25 variability. - Results: we found that Vc,max25 differed across different biomes, with higher mean values in relatively drier regions, and across different life-forms, with higher mean values in non-woody relative to woody plants and in legumes relative to non-leguminous plants. The values of Vc,max25 displayed a significant phylogenetic signal and diverged in a contrasting manner across phylogenetic groups, with a significant trend along the evolutionary axis towards a higher Vc,max25 in more modern clades. A Bayesian phylogenetic linear mixed model revealed that evolutionary history (indicated by phylogeny and species) explained nearly 3-fold more of the variation in global Vc,max25 than present-day environment (53 vs. 18%). - Main conclusions: these findings contribute to a comprehensive assessment of the patterns and drivers of global Vc,max25 variability, highlighting the importance of evolutionary history in driving global Vc,max25 variability, hence terrestrial plant photosynthesis

The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits

The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions

Mars Exploration Rover Pancam Multispectral Imaging of Rocks, Soils, and Dust at Gusev Crater and Meridiani Planum

Multispectral imaging from the Panoramic Camera (Pancam) instruments on the Mars Exploration Rovers Spirit and Opportunity has provided important new insights about the geology and geologic history of the rover landing sites and traverse locations in Gusev crater and Meridiani Planum. Pancam observations from near-UV to near-IR wavelengths provide limited compositional and mineralogic constraints on the presence abundance, and physical properties of ferric- and ferrous-iron bearing minerals in rocks, soils, and dust at both sites. High resolution and stereo morphologic observations have also helped to infer some aspects of the composition of these materials at both sites. Perhaps most importantly, Pancam observations were often efficiently and effectively used to discover and select the relatively small number of places where in situ measurements were performed by the rover instruments, thus supporting and enabling the much more quantitative mineralogic discoveries made using elemental chemistry and mineralogy data. This chapter summarizes the major compositionally- and mineralogically-relevant results at Gusev and Meridiani derived from Pancam observations. Classes of materials encountered in Gusev crater include outcrop rocks, float rocks, cobbles, clasts, soils, dust, rock grindings, rock coatings, windblown drift deposits, and exhumed whitish/yellowish salty soils. Materials studied in Meridiani Planum include sedimentary outcrop rocks, rock rinds, fracture fills, hematite spherules, cobbles, rock fragments, meteorites, soils, and windblown drift deposits. This chapter also previews the results of a number of coordinated observations between Pancam and other rover-based and Mars-orbital instruments that were designed to provide complementary new information and constraints on the mineralogy and physical properties of martian surface materials