Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis

Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis.     

Stargazin modulates AMPA receptor gating and trafficking by distinct domains

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors mediate fast excitatory synaptic transmission in the brain. These ion channels rapidly deactivate and desensitize, which determine the time course of synaptic transmission. Here, we find that the AMPA receptor interacting protein, stargazin, not only mediates AMPA receptor trafficking but also shapes synaptic responses by slowing channel deactivation and desensitization. The cytoplasmic tail of stargazin determines receptor trafficking, whereas the ectodomain controls channel properties. Stargazin alters AMPA receptor kinetics by increasing the rate of channel opening. Disrupting the interaction of stargazin ectodomain with hippocampal AMPA receptors alters the amplitude and shape of synaptic responses, establishing a crucial function for stargazin in controlling the efficacy of synaptic transmission in the brain.     

The nutritional incidence of flavonoids: some physiological and metabolic considerations

Summary Examination of the physiological activity of flavonoids in relation to their antiscorbutic properties shows that some of these compounds, the flavan-3=ols, have a particular nutritional impact and consequently should be distinguished from the rest of the flavonoids and polyphenolds. Therefore, the use of the term Vitamin P and Bioflavonoids is also discussed.     

Redescription of the Cephalaspidea gastropod Atys jeffreysi (Weinkauff, 1866) (Haminoeidae), with a discussion on the phylogenetic affinities of the Mediterranean species of the genus

Atys jeffreysi is a heterobranch Cephalaspidea gastropod belonging to the family Haminoeidae occurring in the Mediterranean Sea, Madeira and Canary archipelagos. Nearly nothing is known about the internal anatomical features of this species. In this paper we redescribe the species A. jeffreysi based on fine anatomical work and scanning electron microscopy. DNA barcodes are provided for the first time for A. jeffreysi and A. macandrewii, the only two species of the genus native in the Mediterranean Sea. The genetic distance (COI uncorrected p-distance) between them is estimate at 21.6%. A Bayesian molecular phylogeny based on the gene marker cytochrome c oxidase subunit I (COI) including all sequences available of the genera Aliculastrum, Liloa and Atys species did not support a sister relationship between the two Mediterranean species and suggests that they are more closely related to distinct Indo-West Pacific lineages. The complex systematics of the genus Atys is briefly discussed.     

基础矩阵估计综合算法的几何意义及分析

研究了基础矩阵参数的几何意义，提出了新的估计基础矩阵的约束条件，首无用给的约束求出Ｆ阵的４个参数，而这２个参数正好是２个对极点的仿射坐标，然后通过解线方程组获得其余４个参数，而这４个参数表示了对极线束间的对应关系，最后，经过对真实图像和合成数据的测试表明本方法有明显的几何意义，可获得几何特性稳定的Ｆ阵。     

The Scientific Interests of Archibald Campbell, 1st Earl of Ilay and 3rd Duke of Argyll (1682-1761)

Amateur scientists were important in the science of the eighteenth century as patrons, investors in talent and new equipment, as the maintainers of gardens and libraries, and, occasionally, as men who could and did make discoveries or significant innovations. The article shows that the 3rd Duke of Argyll was one of these men. He was also much more. Ilay's interests in science, because of his important political position in Scotland, touched not only his immediate friends but helped to reshape Scottish culture itself. This essay looks at his scientific interests, his political career, and his patronage to argue that the results of his long career in politics were to institutionalize a new set of modern values in most Scottish institutions.     

L'acide thymonucléique polymérisé, principe paraissant susceptible de déterminer la spécificité sérologique et l'équipement enzymatique des bactéries. Signification pour la biochimie de l'hérédité

Summary Interactions between two types of bacteria can produce either inhibition of the growth of one of these bacteria or transformation of their biochemical or antigenic properties. Authors have shown and studied one case of induction of a new serological specificity and a new enzymic equipment in aBacterium coli. This induction was produced through a substance liberated, during autolysis, by an otherBacterium coli. Active principle is a thymonucleic acid which, maybe, results from a solubilisation of chromosomes of the inductor bacteria. Hypothesis appears likely.     

生物炭作为无土栽培基质的初步探究

研究柠条深度裂解产生的生物炭作为无土栽培机制的可行性,以探讨柠条的综合开发和利用.试验分析了生物炭和草炭复配基质的理化特性,并对小白菜做育苗期盆栽试验.结果表明:当草炭和柠条炭的质量比为4∶2时达到最佳配比,此时混配基质各项指标均符合理想基质的要求;柠条炭具有强大的吸附能力和丰富的孔隙结构,其作为草炭的混配基质能够较大程度提高基质的透气性和速效钾含量,有贮存和缓释养分的作用.     

The Dark Side of the Moon—Unilluminated Dimensions of Systems Practice

This paper explores some of the unilluminated or less explicit aspects of issues faced by those using systems approaches in real-world problem situations. The paper contends that discourse on systems approaches tends to be dominated by rational logical aspects of methodology, though other aspects of the intervention process, such as political dimensions of legitimacy, have become more important in the last 10–15 years. Unsurprisingly the discourse has been different for different methods. Method has been largely invisible in the hard systems area (or at least relatively little discussed), and although it has been the subject of much debate in the soft systems area, the debate has been nonetheless narrowly defined. It is narrowly defined in its relative neglect of process aspects for conducting a systems study. Since the nature of these processes (for example, the client/consultant relation) changes from hard systems to soft systems to critical systems in a way that makes social process progressively a more important dimension of each approach, this aspect has featured more in discourse on critical systems, but in general it remains a curious area of neglect. There is increasing interest in this area, and some signs that relevant theory and practice from closely related domains is being accessed to strengthen these approaches. This paper attempts to make a contribution by outlining and discussing some areas that could usefully complement existing systems approaches. The paper considers the following areas: (a) client relations, (b) analyst role, (c) language and communication, (d) group processes, (e) culture (and rationalities), (f) information gathering techniques and processes, and (g) change management or implementation. The paper draws on experiences of systems practices in the literature, interviews with systems practitioners, and writings in related areas. The paper ends by discussing some of the implications of these issues for the development of well-rounded systems approaches.