Influencing the secretion of myogenic factors from mesenchymal stem cells.

Mounting evidence indicates that the regenerative effect of mesenchymal stem cells in skeletal muscle is related to the secretion of factors that stimulate resident myogenic cells. However, the environmental cues that affect the secreted factors of mesenchymal stem cells are not well understood. A recent publication demonstrated that secretion of factors is dependent on cell substrate, with mesenchymal stem cells grown on laminin providing more pro-myogenic factors than those grown on collagen, and that cellular strain may also play a role. Conditioned media from mesenchymal stem cells grown on laminin and subjected to strain provided the quickest and largest stimulation to myogenic cell proliferation. The influence of cell substrate and mechanical perturbation on mesenchymal stem cells therefore appears key to secretion of factors that support myogenesis

Competitive market for multiple firms and economic crisis

The origin of economic crises is a key problem for economics. We present a model of long-run competitive markets to show that the multiplicity of behaviors in an economic system, over a long time scale, emerge as statistical regularities (perfectly competitive markets obey Bose-Einstein statistics and purely monopolistic-competitive markets obey Boltzmann statistics) and that how interaction among firms influences the evolutionary of competitive markets. It has been widely accepted that perfect competition is most efficient. Our study shows that the perfectly competitive system, as an extreme case of competitive markets, is most efficient but not stable, and gives rise to economic crises as society reaches full employment. In the economic crisis revealed by our model, many firms condense (collapse) into the lowest supply level (zero supply, namely bankruptcy status), in analogy to Bose-Einstein condensation. This curious phenomenon arises because perfect competition (homogeneous competitions) equals symmetric (indistinguishable) investment direction, a fact abhorred by nature. Therefore, we urge the promotion of monopolistic competition (heterogeneous competitions) rather than perfect competition. To provide early warning of economic crises, we introduce a resolving index of investment, which approaches zero in the run-up to an economic crisis. On the other hand, our model discloses, as a profound conclusion, that the technological level for a long-run social or economic system is proportional to the freedom (disorder) of this system; in other words, technology equals the entropy of system. As an application of this new concept, we give a possible answer to the Needham question: "Why was it that despite the immense achievements of traditional China it had been in Europe and not in China that the scientific and industrial revolutions occurred?"Comment: 17 pages; 3 figure

Methods to prioritise pop-up active transport infrastructure and their application in a national cycleway prioritisation tool

In the context of reduced public transport capacity in the wake of the COVID-19 pandemic, governments are scrambling to enable walking and cycling while adhering to physical distancing guidelines. Many pop-up options exist. Of these, road space reallocation represents a ‘quick win’ for cities with ‘spare space’ along continuous road sections that have high latent cycling potential. We developed methods to condense the complexity of city networks down to the most promising roads for road space reallocation schemes. The resulting Rapid Cycleway Prioritisation Tool has been deployed for all cities in England to help prioritise emergency funds for new cycleways nationwide. The methods and concepts could be used to support investment in pop-up infrastructure in cities worldwide

Influencing the secretion of myogenic factors from mesenchymal stem cells

Mounting evidence indicates that the regenerative effect of mesenchymal stem cells in skeletal muscle is related to the secretion of factors that stimulate resident myogenic cells. However, the environmental cues that affect the secreted factors of mesenchymal stem cells are not well understood. A recent publication demonstrated that secretion of factors is dependent on cell substrate, with mesenchymal stem cells grown on laminin providing more pro-myogenic factors than those grown on collagen, and that cellular strain may also play a role. Conditioned media from mesenchymal stem cells grown on laminin and subjected to strain provided the quickest and largest stimulation to myogenic cell proliferation. The influence of cell substrate and mechanical perturbation on mesenchymal stem cells therefore appears key to secretion of factors that support myogenesis

Functional muscle hypertrophy by increased insulin-like growth factor 1 does not require dysferlin.

IntroductionDysferlin loss-of-function mutations cause muscular dystrophy, accompanied by impaired membrane repair and muscle weakness. Growth promoting strategies including insulin-like growth factor 1 (IGF-1) could provide benefit but may cause strength loss or be ineffective. The objective of this study was to determine whether locally increased IGF-1 promotes functional muscle hypertrophy in dysferlin-null (Dysf-/- ) mice.MethodsMuscle-specific transgenic expression and postnatal viral delivery of Igf1 were used in Dysf-/- and control mice. Increased IGF-1 levels were confirmed by enzyme-linked immunosorbent assay. Testing for skeletal muscle mass and function was performed in male and female mice.ResultsMuscle hypertrophy occurred in response to increased IGF-1 in mice with and without dysferlin. Male mice showed a more robust response compared with females. Increased IGF-1 did not cause loss of force per cross-sectional area in Dysf-/- muscles.DiscussionWe conclude that increased local IGF-1 promotes functional hypertrophy when dysferlin is absent and reestablishes IGF-1 as a potential therapeutic for dysferlinopathies

Testing General Relativity with Current Cosmological Data

Deviations from general relativity, such as could be responsible for the cosmic acceleration, would influence the growth of large scale structure and the deflection of light by that structure. We clarify the relations between several different model independent approaches to deviations from general relativity appearing in the literature, devising a translation table. We examine current constraints on such deviations, using weak gravitational lensing data of the CFHTLS and COSMOS surveys, cosmic microwave background radiation data of WMAP5, and supernova distance data of Union2. Markov Chain Monte Carlo likelihood analysis of the parameters over various redshift ranges yields consistency with general relativity at the 95% confidence level.Comment: 11 pages; 7 figures; typographical errors corrected; this is the published versio