Mantle segmentation along the Oman ophiolite fossil mid-ocean ridge

It has been difficult to relate the segmentation of mid-ocean ridges to processes occurring in the Earth's underlying mantle, as the mantle is rarely sampled directly and chemical variations observed in lavas at the surface are heavily influenced by details of their production as melt extracted from the mantle. Our understanding of such mantle processes has therefore relied on the analysis of pieces of fossil oceanic lithosphere now exposed at the Earth's surface, known as ophiolites. Here we present the phase chemistry and whole-rock major- and trace-element contents of 174 samples of the mantle collected along over 400 km of the Oman Sultanate ophiolite. We show that, when analysed along the fossil ridge, variations of elemental ratios sensitive to the melting process define a three-dimensional geometry of mantle upwellings, which can be related to the segmentation observed in modern mid-ocean ridge environments.     

Wallis's product,Brouncker's continued fraction,and Leibniz's series

A historical sketch is given of Wallis's infinite product for 4/, and of the attempts which have been made, over more than three centuries, to find the method by which Brouncker obtained his equivalent continued fraction. A derivation of Brouncker's formula is given. Early results obtained by Indian mathematicians for the series for /4, later named for Leibniz, are reviewed and extended. A conjecture is made concerning Brouncker's method of obtaining close bounds for .     

Trace element characteristics of a Gorham-Stout Syndrome sufferer

Gorham-Stout Syndrome （GSS） is an infrequent and mysterious bone disease characterized by massive bone dissolving or even disappearing due to an unknown pathogeny. It is quite different from the Itai-itai disease and osteoporosis. In 2001, an 8-year-old boy from a small town in Xinjiang was found to get GSS disease. Some parts of his bones vanished without any external force. Results showed that the concentrations of Cd and Cu, especially Na and K in his hair were far higher than those of the healthy people, and the concentration of Cd was 2 times that of the reference while those of Cr and Zn were insufficient for health. The ratio of K/Na was also higher than that of healthy group. Four different ratios revealed weak bone growth potential and strong bone breakage occurred simultaneously in the GSS sufferer＇s skeletal system. It might be the synergistic effect of the trace elements leading to the baffling syndrome. Further investigation demonstrated that the trace elements can cause a series of diseases, including GSS disease and a typical rheumatoid arthritis （ARA）. Epidemiological investigation also proved that there were about 25% of the inhabitants in the town suffered from an ARA. All of these data implied there was significant relationship among Gorham-Stout Syndrome, ARA and prolapse of lumbar intervertebral disc.     

Evolution of nonclassical MHC-dependent invariant T cells

TCR-mediated specific recognition of antigenic peptides in the context of classical MHC molecules is a cornerstone of adaptive immunity of jawed vertebrate. Ancillary to these interactions, the T cell repertoire also includes unconventional T cells that recognize endogenous and/or exogenous antigens in a classical MHC-unrestricted manner. Among these, the mammalian nonclassical MHC class I-restricted invariant T cell (iT) subsets, such as iNKT and MAIT cells, are now believed to be integral to immune response initiation as well as in orchestrating subsequent adaptive immunity. Until recently the evolutionary origins of these cells were unknown. Here we review our current understanding of a nonclassical MHC class I-restricted iT cell population in the amphibian Xenopus laevis. Parallels with the mammalian iNKT and MAIT cells underline the crucial biological roles of these evolutionarily ancient immune subsets.     

Retinoic acid maintains human skeletal muscle progenitor cells in an immature state

Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3. These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors.     

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP.     

PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome

We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.44; rs1975197, P(nominal/lambda corrected) = 5.81 x 10(-9), OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.