Bioenergetics Failure and Oxidative Stress in Brain Stem Mediates Cardiovascular Collapse Associated with Fatal Methamphetamine Intoxication

Background: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH), the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. Methodology/Principal Findings: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemica

Climate-Smart Groundnuts for Achieving High Productivity and Improved Quality: Current Status, Challenges, and Opportunities

About 90% of total groundnut is cultivated in the semi-arid tropic (SAT) regions of the world as a major oilseed and food crop and provides essential nutrients required by human diet. Climate change is the main threat to yield and quality of the produce in the SAT regions, and effects are already being seen in some temperate areas also. Rising CO2 levels, erratic rainfall, humidity, short episodes of high temperature and salinity hamper the physiology, disease resistance, fertility and yield as well as seed nutrient levels of groundnut. To meet growing demands of the increasing population against the threats of climate change, it is necessary to develop climate-smart varieties with enhanced and stable genetic improvements. Identifying key traits affected by climate change in groundnut will be important for developing an appropriate strategy for developing new varieties. Fast-changing scenarios of product ecologies as a consequence of climate change need faster development and replacement of improved varieties in the farmers’ fields to sustain yield and quality. Use of modern genomics technology is likely to help in improved understanding and efficient breeding for climate-smart traits such as tolerance to drought and heat, and biotic stresses such as foliar diseases, stem rot, peanut bud necrosis disease, and preharvest aflatoxin contamination. The novel promising technologies such as genomic selection and genome editing need to be tested for their potential utility in developing climate-smart groundnut varieties. System modeling may further improve the understanding and characterization of the problems of target ecologies for devising strategies to overcome the problem. The combination of conventional breeding techniques with genomics and system modeling approaches will lead to a new era of system biology assisted breeding for sustainable agricultural production to feed the ever-growing population