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

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Modeling wildlife and other trade-offs with biofuel crop production

Biofuels from agricultural sources are an important part of California's strategy to reduce greenhouse gas emissions and dependence on foreign oil. Land conversion for agricultural and urban uses has already imperiled many animal species in the state. This study investigated the potential impacts on wildlife of shifts in agricultural activity to increase biomass production for transportation fuels. We applied knowledge of the suitability of California's agricultural landscapes for wildlife species to evaluate wildlife effects associated with plausible scenarios of expanded production of three potential biofuel crops (sugar beets, bermudagrass, and canola). We also generated alternative, spatially explicit scenarios that minimized loss of habitat for the same level of biofuel production. We explored trade-offs to compare the marginal changes per unit of energy for transportation costs, wildlife, land and water-use, and total energy produced, and found that all five factors were influenced by crop choice. Sugar beet scenarios require the least land area: 3.5 times less land per liter of gasoline equivalent than bermudagrass and five times less than canola. Canola scenarios had the largest impacts on wildlife but the greatest reduction in water use. Bermudagrass scenarios resulted in a slight overall improvement for wildlife over the current situation. Relatively minor redistribution of lands converted to biofuel crops could produce the same energy yield with much less impact on wildlife and very small increases in transportation costs. This framework provides a means to systematically evaluate potential wildlife impacts of alternative production scenarios and could be a useful complement to other frameworks that assess impacts on ecosystem services and greenhouse gas emissions. © 2011 Blackwell Publishing Ltd

Tactile Afferent Input Influencing Motor Coordination During Precision Grip

The remarkable capacity and versatility of the human hand in precise manipula-tory tasks is undoubtedly dependent upon a number of neural factors. One such factor is the tactile sensory innervation of the glabrous skin area, i.e. the hairless skin of the volar aspect of the hand. Indeed, Mott and Sherrington [22], dealing with the motor effects of various patterns of dorsal root sections in Macacus rhesus, found that "afferent impulses, both from the skin and from muscles, espe-cially the former, as related to the palm and sole, are necessary for the carrying out of 'highest level ' movements. " Likewise, Denny-Brown [5] wrote extensively on the capacity of tactile stimuli in eliciting prepatterned integrated hand move-ments in clinical and experimental material. In patients with frontal lobe lesions, automatic prehensile movements of at least two types could be distinguished: the "grasp reflex " and the more complex "instinctive grasp reaction". In contrast, during parietal lobe lesions, "tactile avoiding reactions " of different complexities were described. The pathological feature of these reactions was considered to be an inability to adequately suppress the first phase, i.e. the reactions appeared t