Anti-DLST monoclonal antibody, clone 5E8

Trimethylamine-N-oxide (TMAO), a microbial choline metabolism byproduct that is processed in the liver and excreted into circulation, is associated with increased atherosclerotic lesion formation and cardiovascular disease risk. Genetic regulators of TMAO levels are largely unknown. In the present study, we used 288 mice from a genetically heterogeneous mouse population [Diversity Outbred (DO)] to determine hepatic microRNA associations with TMAO in the context of an atherogenic diet. We also validated findings in two additional animal models of atherosclerosis: liver-specific insulin receptor knockout mice fed a chow diet (LIRKO) and African green monkeys fed high-fat/high-cholesterol diet. Small RNA-sequencing analysis in IX) mice, LIRKO mice, and African green monkeys identified only one hepatic microRNA (miR-146a-5p) that is aberrantly expressed across all three models. Moreover, rniR-146a-5p levels are associated with circulating TMAO after atherogenic diet in each of these models. We also performed high-resolution genetic mapping and identified a novel quantitative trait locus on Chromosome 12 for TMAO levels. This interval includes two genes. Numb and Dist, which are inversely correlated with both miR-146a and TMAO and are predicted targets of miR-146a. Both of these genes have been validated as direct targets of miR-146a, though in other cellular contexts. This is the first report to our knowledge of a link between miR-146 and TMAO. Our findings suggest that miR-146-5p, as well as one or more genes at the Chromosome 12 QTL (possibly Numb or Dlst), is strongly linked to TMAO levels and likely involved in the control of atherosclerosis.

Progressive collapse of space structures has received much attention in recent years due to the recent failure of a double-layer space truss (DLST) stadium in Terengganu, Malaysia which collapse twice in Year 2009 and 2013. There is a considerable interest in understanding the collapse behaviour of space structures and possibility of improving its collapse behaviour. This phenomenon was demonstrated by earlier researchers, such as Collins (1981) and Parke (1988) which investigated the collapse behaviour both theoretically and experimentally. In their study a carefully designed DLST structure may possess reserve of strength in excess of their elastic capacity. Although DLST have a high degree of statically degree of statically indeterminacy, not all of them are robust, as it has been found a loss of one critical member could trigger the collapse of the entire structure. Usually the collapse of the DLST is influenced by the ductility behaviour of the compression members. The aim of this study was to investigate the use of novel soft member to reduce the catastrophic progressive collapse behaviour of DLSTs. A novel soft member was constructed to measure its behaviour under tensile and compressive loads. The term novel soft member used in this study is referred to a combination of three circular tubes which is made into one component and is used to support compressive load. It was found that using a blend of three circular tubes significantly increase the ductility behaviour of the member. These test illustrates that while the inner and outer tube experience compressive forces, the middle tube will continue to increase linearly. This indicates that there is a possibility of improving the collapse behaviour of DLST by incorporating the novel soft member.