Testing Gravity with Pulsars in the SKA Era

The Square Kilometre Array (SKA) will use pulsars to enable precise measurements of strong gravity effects in pulsar systems, which yield tests of gravitational theories that cannot be carried out anywhere else. The Galactic census of pulsars will discover dozens of relativistic pulsar systems, possibly including pulsar -- black hole binaries which can be used to test the "cosmic censorship conjecture" and the "no-hair theorem". Also, the SKA's remarkable sensitivity will vastly improve the timing precision of millisecond pulsars, allowing probes of potential deviations from general relativity (GR). Aspects of gravitation to be explored include tests of strong equivalence principles, gravitational dipole radiation, extra field components of gravitation, gravitomagnetism, and spacetime symmetries.Comment: 20 pages, 4 figures, to be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14)04

Cordyceps Sinensis: anti-fibrotic and inflammatory effects of a cultured polysaccharide extract

It has been suggested that the traditional Chinese herbal preparation Cordyceps Sinensis (CS) may have a beneficial effect in renal disease. To satisfy increasing demand, CS derivatives have been produced by aseptic mycelia cultivation. We have demonstrated antifibrotic activity of cultured CS previously. The aim of this study was to examine bioactivity of a polysaccharide isolated from cultured CS with a complicated monosaccharide composition, mainly consisting of Gal, Glc and Man. This polysaccharide antagonised the effect of TGF-b1 in stimulating the expression of collagen in the HK2 renal cell line. This was associated with down regulation of the TGF-b receptor Alk5. In addition the polysaccharide antagonised IL-1b stimulated sICAM-1 dependent adherence of monocytes to a monolayer of HK2 cell. This was associated with increased expression of the primary receptor for hyaluronan CD44, and was abrogated by removal of the cell surface hyaluronan pericellular coat. In summary we describe both anti-fibrotic and anti-inflammatory activity in a polysaccharide isolated from cultured CS

Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar

Biorefineries aim to convert biomass to a spectrum of products ranging from biofuels to specialty chemicals. To achieve economically sustainable conversion it is crucial to streamline the catalytic and downstream processing steps. Here we report a route that integrates bio- and chemical catalysis to convert glucose into bio-based unsaturated nylon 6,6. An engineered strain of Saccharomyces cerevisiae, with the highest reported muconic acid titer of 559.5 mg L-1 in yeast, was used as the initial biocatalyst to convert glucose into muconic acid. Without any separation, muconic acid was further electrocatalytically hydrogenated to 3-hexenedioic acid with 94% yield, despite the presence of all the biogenic impurities. Bio-based unsaturated nylon 6,6 (unsaturated polyamide 6,6) was finally obtained by polymerization of 3-hexenedioic acid with hexamethylenediamine, demonstrating the integrated design of bio-based polyamides from glucose

Presenilin1 familial Alzheimer disease mutants inactivate EFNB1- and BDNF-dependent neuroprotection against excitotoxicity by affecting neuroprotective complexes of N-methyl-d-aspartate receptor

Excitotoxicity is thought to play key roles in brain neurodegeneration and stroke. Here we show that neuroprotection against excitotoxicity by trophic factors EFNB1 and brain-derived neurotrophic factor (called here factors) requires de novo formation of 'survival complexes' which are factor-stimulated complexes of N-methyl-D-aspartate receptor with factor receptor and presenilin 1. Absence of presenilin 1 reduces the formation of survival complexes and abolishes neuroprotection. EPH receptor B2- and N-methyl-D-aspartate receptor-derived peptides designed to disrupt formation of survival complexes also decrease the factor-stimulated neuroprotection. Strikingly, factor-dependent neuroprotection and levels of the de novo factor-stimulated survival complexes decrease dramatically in neurons expressing presenilin 1 familial Alzheimer disease mutants. Mouse neurons and brains expressing presenilin 1 familial Alzheimer disease mutants contain increased amounts of constitutive presenilin 1-N-methyl-D-aspartate receptor complexes unresponsive to factors. Interestingly, the stability of the familial Alzheimer disease presenilin 1-N-methyl-D-aspartate receptor complexes differs from that of wild type complexes and neurons of mutant-expressing brains are more vulnerable to cerebral ischaemia than neurons of wild type brains. Furthermore, N-methyl-D-aspartate receptor-mediated excitatory post-synaptic currents at CA1 synapses are altered by presenilin 1 familial Alzheimer disease mutants. Importantly, high levels of presenilin 1-N-methyl-D-aspartate receptor complexes are also found in post-mortem brains of Alzheimer disease patients expressing presenilin 1 familial Alzheimer disease mutants. Together, our data identify a novel presenilin 1-dependent neuroprotective mechanism against excitotoxicity and indicate a pathway by which presenilin 1 familial Alzheimer disease mutants decrease factor-depended neuroprotection against excitotoxicity and ischaemia in the absence of Alzheimer disease neuropathological hallmarks which may form downstream of neuronal damage. These findings have implications for the pathogenic effects of familial Alzheimer disease mutants and therapeutic strategies.This work was supported by National Institutes of Health grants 2RF1AG008200-29; 2R01-NS047229; P50AG05138; and by Grant AARF-17-531426 of the Alzheimer's Association