Clusterin facilitates in vivo clearance of extracellular misfolded proteins

The extracellular deposition of misfolded proteins is a characteristic of many debilitating age-related disorders. However, little is known about the specific mechanisms that act to suppress this process in vivo. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes with misfolded client proteins. Here we explore the fate of complexes formed between CLU and misfolded proteins both in vitro and in a living organism. We show that proteins injected into rats are cleared more rapidly from circulation when complexed with CLU as a result of their more efficient localization to the liver and that this clearance is delayed by pre-injection with the scavenger receptor inhibitor fucoidan. The CLU–client complexes were found to bind preferentially, in a fucoidan-inhibitable manner, to human peripheral blood monocytes and isolated rat hepatocytes and in the latter cell type were internalized and targeted to lysosomes for degradation. The data suggest, therefore, that CLU plays a key role in an extracellular proteostasis system that recognizes, keeps soluble, and then rapidly mediates the disposal of misfolded proteins.     

Livestock and vegetation responses to rotational grazing in short-grass steppe

There is a paucity of information concerning livestock and vegetation responses to rotational grazing in short-grass steppe. We compared effects between 1995 and 2003 of time-controlled, short-duration rotational grazing against season-long continuous grazing, at a moderate stocking rate (1.95 ha ? animal unit month –1 ), on livestock gains and on foliar and basal cover in short-grass steppe. Livestock average daily gains, grazing-season gains, and beef production did not differ between grazing systems. We observed no relationship between precipitation (annual or growing-season) and average daily gain. In contrast, both grazing-season gains and beef production exhibited a significant curvilinear response to both growing-season and annual precipitation. Basal and foliar cover of all plant functional groups (C 3 annual grasses, C 3 perennial grasses and grass-likes, C 4 perennial grasses, cactus, annual forbs, perennial forbs, and shrubs/subshrubs) did not differ between grazing systems. Litter and bare ground were also unaffected by grazing system, with litter increasing and bare ground decreasing over the duration of this experiment. Land managers in shortgrass steppe who are implementing rotational grazing at moderate stocking rates should not expect increased livestock gains or changes in basal and foliar cover of the plant community. Rotational grazing may be a useful management tool for achieving conservation goals through modifications of seasonality and intensity of use in paddocks within larger management units to accommodate spatial variability in vegetation and temporal variation in precipitation.     

Emergence of a new disease as a result of interspecific virulence gene transfer

New diseases of humans, animals and plants emerge regularly. Enhanced virulence on a new host can be facilitated by the acquisition of novel virulence factors. Interspecific gene transfer is known to be a source of such virulence factors in bacterial pathogens (often manifested as pathogenicity islands in the recipient organism) and it has been speculated that interspecific transfer of virulence factors may occur in fungal pathogens. Until now, no direct support has been available for this hypothesis. Here we present evidence that a gene encoding a critical virulence factor was transferred from one species of fungal pathogen to another. This gene transfer probably occurred just before 1941, creating a pathogen population with significantly enhanced virulence and leading to the emergence of a new damaging disease of wheat.     

Neural population dynamics during reaching

Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.     

Can patents prohibit research? On the social epistemology of patenting and licensing in science

A topic of growing importance within philosophy of science is the epistemic implications of the organization of research. This paper identifies a promising approach to social epistemology—nonideal systems design—and uses it to examine one important aspect of the organization of research, namely the system of patenting and licensing and its role in structuring the production and dissemination of knowledge. The primary justification of patenting in science and technology is consequentialist in nature. Patenting should incentivize research and thereby promote the development of knowledge, which in turn facilitates social progress. Some have disputed this argument, maintaining that patenting actually inhibits knowledge production. In this paper, I make a stronger argument; in some areas of research in the US—in particular, research on GM seeds—patents and patent licenses can be, and are in fact being, used to prohibit some research. I discuss three potential solutions to this problem: voluntary agreements, eliminating patents, and a research exemption. I argue against eliminating patents, and I show that while voluntary agreements and a research exemption could be helpful, they do not sufficiently address the problems of access that are discussed here. More extensive changes in the organization of research are necessary.     

Optically healable supramolecular polymers

Polymers with the ability to repair themselves after sustaining damage could extend the lifetimes of materials used in many applications. Most approaches to healable materials require heating the damaged area. Here we present metallosupramolecular polymers that can be mended through exposure to light. They consist of telechelic, rubbery, low-molecular-mass polymers with ligand end groups that are non-covalently linked through metal-ion binding. On exposure to ultraviolet light, the metal-ligand motifs are electronically excited and the absorbed energy is converted into heat. This causes temporary disengagement of the metal-ligand motifs and a concomitant reversible decrease in the polymers' molecular mass and viscosity, thereby allowing quick and efficient defect healing. Light can be applied locally to a damage site, so objects can in principle be healed under load. We anticipate that this approach to healable materials, based on supramolecular polymers and a light-heat conversion step, can be applied to a wide range of supramolecular materials that use different chemistries.     

Long-term evolution and transmission dynamics of swine influenza A virus

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12?years of systematic surveillance in this region, supplemented with data stretching back 34?years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.