GENE EXPRESSION FOLLOWING TRAUMATIC BRAIN INJURY

The pathology which results from traumatic brain injury (TBI) have long been believed to be immediate and irreversible. However, recently it has been shown that, although the primary effects are virtually unavoidable, the secondary effects manifest themselves through biochemical processes set in motion at the time of the injury. These events are frequently mediated through the process of excitotoxicity, which results from a widespread release of excitatory neurotransmitters. These neurotransmitters go on to activate both ionotropic and metabotropic receptors. The signal transduction initiated through these receptor populations gives rise to changes in gene expression. One result of this release of neurotransmitter is an influx of calcium by means of excitatory receptors on the cell. The neurotransmitters upon which most research is focused are glutamate, aspartate, and acetylcholine. Current research is aimed at investigating antagonists to this process as well as elucidating steps within the process. Antagonists primarily function to reduce the calcium toxicity through modulation of receptor activity. However, the therapeutic window for effective antagonist usage is short. Therefore, although they may represent a viable treatment option, they need to be administered as early as possible following the injury to have the greatest effect. The purpose of this paper is to provide a summary of the available literature on TBI and excitotoxicity with a focus on changes in gene regulation. This paper will summarize information on the steps inVolved in the intracellular signaling cascade following brain injury and provide insight to further sites for regulation and treatment. This will also allow for development hypotheses on the possible roles of some of the genes whose expression is already known to be altered

The aftermath of coronavirus disease of 2019: devastation or a new dawn for nephrology?

The acute crisis with the coronavirus disease of 2019 (COVID-19) caused by the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) is the largest biomedical catastrophe of our lifetimes. Like so many other disasters in the past, such as war, famine, social unrest and economic calamities, this too shall pass, but it will undoubtedly leave the world changed. Some of the changes are already evident, but some are inevitable once we get over this pandemic. In this perspective, I provide examples of how the virus is already inducing change in the practice of medicine at large and for nephrology in particular. As is true for many changes, some persist after the emergency is over, so I speculate on how nephrology may change once we surmount this predicament (Figure 1)

The molecular genetics and cellular mechanisms underlying pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards

QCD Critical Point: The Race is On

A critical point in the phase diagram of Quantum Chromodynamics (QCD), if established either theoretically or experimentally, would be as profound a discovery as the good-old gas-liquid critical point. Unlike the latter, however, first-principles based approaches are being employed to locate it theoretically. Due to the short lived nature of the concerned phases, novel experimental techniques are needed to search for it. The Relativistic Heavy Ion Collider (RHIC) in USA has an experimental program to do so. This short review is an attempt to provide a glimpse of the race between the theorists and the experimentalists as well as that of the synergy between them.Comment: 15 Pages, Invited Review for Praman

Stability of Equilibria in Games with Procedurally Rational Players

One approach to the modeling of bounded rationality in strategic environments is based on the dynamics of evolution and learning in games. An entirely different approach has been developed recently by Osborne and Rubinstein (1998). This latter approach is static and equilibrium based, but relies on less stringent assumptions regarding the knowledge and understanding of players than does the standard theory of Nash equilibrium. This paper formalizes Osborne and Rubinstein's dynamic interpretation of their equilibrium concept and thereby facilitates a comparison of this approach with the explicitly dynamic approach of evolutionary game theory. It turns out that the two approaches give rise to radically different static and dynamic predictions. For instance, dynamically stable equilibria can involve the playing of strictly dominated actions, and equilibria in which strictly actions are played with probability 1 can be unstable. Sufficient conditions for the instability of equilibria are provided for symmetric and asymmetric games.Dynamic Stability, S(1) Equilibrium, Procedural Rationality, Evolutionary Games