Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

Background  

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.     

Direct utilization of mannose for mammalian glycoprotein biosynthesis

Direct utilization of mannose for glycoprotein biosynthesis has not been studied because cellular mannose is assumed to be derived entirely from glucose. However, animal sera contain sufficient mannose to force uptake through glucose-tolerant, mannose-specific transporters. Under physiological conditions this transport system provides 75% of the mannose for protein glycosylation in human hepatoma cells despite a 50- to 100-fold higher concentration of glucose. This suggests that direct use of mannose is more important than conversion from glucose. Consistent with this finding the liver is low in phosphomannose isomerase activity (fructose-6-P<->mannose-6-P), the key enzyme for supplying glucose-derived mannose to the N-glycosylation pathway. [2- 3H] Mannose is rapidly absorbed from the intestine of anesthetized rats and cleared from the blood with a t1/2of 30 min. After a 30 min lag, label is incorporated into plasma glycoproteins, and into glycoproteins of all organs during the first hour. Most (87%) of the initial incorporation occurs in the liver, but this decreases as radiolabeled plasma glycoproteins increase. Radiolabel in glycoproteins also increases 2- to 6-fold in other organs between 1-8 h, especially in lung, skeletal muscle, and heart. These organs may take up hepatic- derived radiolabeled plasma glycoproteins. Significantly, the brain, which is not exposed to plasma glycoproteins, shows essentially no increase in radiolabel. These results suggest that mammals use mannose transporters to deliver mannose from blood to the liver and other organs for glycoprotein biosynthesis. Additionally, contrary to expectations, most of the mannose for glycoprotein biosynthesis in cultured hepatoma cells is derived from mannose, not glucose. Extracellular mannose may also make a significant contribution to glycoprotein biosynthesis in the intact organism.      

Evolution of mammalian X-linked and autosomal Pgk and Pdh E1 alpha subunit genes

The phylogeny and substitution rates of the mammalian X chromosome- located and autosomal phosphoglycerate kinase and pyruvate dehydrogenase genes were investigated. Compatibility analysis was used to show reticulate evolution in these genes. Analysis of the marsupial, mouse, and human phosphoglycerate kinase genes suggests that at least two recombination events have taken place, one occurring about the time of the placental-marsupial split involving exons 1-5 and the other before the primate-rodent split involving exons 9-10. Similar analysis of the pyruvate dehydrogenase genes indicates a recombination event involving exons 2-3 at a time before the primate-rodent split and a gene conversion between exons 3-4 in the human somatic and testis- specific pyruvate dehydrogenase genes after the primate-rodent split. This demonstrates that genetic exchange can occur between paralogous genes at widely separated chromosomal locations. Estimation of nucleotide substitution rates in these genes confirmed a higher substitution rate in the pyruvate dehydrogenase genes. In the phosphoglycerate kinase genes, there is no difference between the substitution rates in mice and humans and between the X chromosome- and autosome-located genes. A greater substitution rate was noted in the mouse autosomal pyruvate dehydrogenase gene when compared with the other mouse and human genes. This may be a result of either directional natural selection or a relaxation of functional constraint at this specific gene.      

Multi-objective Task Scheduling in cloud-fog computing using goal programming approach

Cluster Computing - Fog Computing continues to extend its usage by solving cloud computing challenges about Internet of Things (IoT). Fog nodes as a processing resource, can perform tasks generated...     

Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

Background  

Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death signal that sequentially increases (pro-life) and decreases (pro-death) to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1) and nitric oxide synthase I (NOS I)/protein kinase G (PKG) cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death.