An osteocalcin-deficient mouse strain without endocrine abnormalities

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc– ) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, μCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc− allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/ 2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution

An Antecedence Graph Approach for Fault Tolerance in a Multi-Agent

In this paper, we propose a strategy to implement fault-tolerance in a multi-agent system. We have based our strategy on the concept of antecedence graphs, used in causal logging and as used by the manetho protocol for distributed systems. Each agent in the multi-agent system keeps an antecedence graph of all the collaborating agents in the system. If one or more agents fail due to any reason, the other agents can reconstruct the same agent state in a partial or comprehensive manner by using their own antecedence graphs. The recovering agents then regenerate their antecedence graphs and message logs and replay the messages to achieve a global consistent state, after which normal operation continues. We believe that introducing fault tolerance in a multi-agent system through antecedence graphs is novel and provides a low overhead and effective solution for fault-tolerance in a multi-agent system

Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency.

In a consanguineous Pakistani family with two affected individuals, a homozygous variant Gly399Val in the eighth transmembrane domain of the taurine transporter SLC6A6 was identified resulting in a hypomorph transporting capacity of ~15% compared with normal. Three-dimensional modeling of this variant has indicated that it likely causes displacement of the Tyr138 (TM3) side chain, important for transport of taurine. The affected individuals presented with rapidly progressive childhood retinal degeneration, cardiomyopathy and almost undetectable plasma taurine levels. Oral taurine supplementation of 100 mg/kg/day resulted in maintenance of normal blood taurine levels. Following approval by the ethics committee, a long-term supplementation treatment was introduced. Remarkably, after 24-months, the cardiomyopathy was corrected in both affected siblings, and in the 6-years-old, the retinal degeneration was arrested, and the vision was clinically improved. Similar therapeutic approaches could be employed in Mendelian phenotypes caused by the dysfunction of the hundreds of other molecular transporters

Vitamin A deficiency and other factors associated with severe tuberculosis in Timor and Rote Islands, East Nusa Tenggara Province, Indonesia.

Item does not contain fulltextBACKGROUND: Plasma zinc and vitamin A concentrations have been reported to be low in tuberculosis (TB) patients in some studies, although it is not clear whether this constitutes a risk for a more severe clinical presentation among TB patients. The acute phase reaction may also deplete zinc and vitamin A in the plasma. Therefore, we further studied these associations. METHODS: We carried out a cross-sectional study among newly diagnosed sputum smear-positive TB patients in East Nusa Tenggara. The patients were categorized as either mild TB when Karnofsky Score (KS) > or =80 or severe TB (KS <80). Body mass index (BMI), mid upper arm circumference (MUAC), chest radiograph, and the results of hemoglobin, erythrocyte sedimentation rate, albumin, C-reactive protein (CRP), zinc and vitamin A in plasma were correlated with TB category. RESULTS: A total of 300 TB patients participated in the study (63% male and 37% female), and were categorized as mild TB (53%) or severe TB (47%). Vitamin A, hemoglobin and plasma albumin were significantly lower, and CRP was significantly higher, in severe TB than in mild TB, and the active lesion area on the chest radiograph was greater among severe TB patients. In a multiple regression analysis, after adjustment for CRP, low vitamin A (beta=3.2, 95%CI (confidence interval) 1.6-4.9, P=0.000) but not zinc, correlated with the severity of TB. MUAC was better than BMI as a predictor of TB severity (beta=1.3, 95%CI 0.6-6.2, P=0.000). CONCLUSIONS: Severe TB was associated with vitamin A deficiency. MUAC can be applied as a measure of TB severity

A scrape-through piezoelectric MEMS energy harvester with frequency broadband and up-conversion behaviors

10.1007/s00542-011-1361-4Microsystem Technologies17121747-175