Identification of Novel Inhibitors of DNA Ligase (LigA).

Present in all organisms, DNA ligases catalyse the formation of a phosphodiester bond between a 3' hydroxyl and a 5' phosphate, a reaction that is essential for maintaining genome integrity during replication and repair. Eubacterial DNA ligases use NAD as a cofactor and possess low sequence and structural homology relative to eukaryotic DNA ligases which use ATP as a cofactor. These key differences enable specific targeting of bacterial DNA ligases as an antibacterial strategy.

Use of Arterial Spin-Labeling in Patients with Aneurysmal Sub-arachnoid hemorrhage.

Delayed cerebral ischemia (DCI) due to cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has long been recognized as a major source of morbidity and mortality. Early detection of cerebral vasospasm and identification of patients who are likely to become symptomatic is crucial to guide aggressive medical and/or endovascular interventions. Magnetic resonance imaging using arterial spin-label (ASL) is a noninvasive mean for assessing cerebral blood flow and is based on direct magnetic labeling of arterial blood water protons.

Seizure Prophylaxis in the Immediate Post-Hemorrhagic Period in Patients with Aneurysmal Subarachnoid Hemorrhage.

Introduction: Seizures are a well-known complication of aneurysmal subarachnoid hemorrhage (aSAH) and occur most commonly in the immediate posthemorrhagic period. Most commonly used antiepileptic drugs (AEDs) for seizure prophylaxis in aSAH include phenytoin and levetiracetam. There is no reliable data available on the safety and efficacy of restricting AED prophylaxis only till the aneurysm is secured.

Dimethyl fumarate ameliorates myoclonus stemming from protein misfolding in oligodendrocytes.

Multiple sclerosis (MS) is considered a primary autoimmune disease; however, this view is increasingly being challenged in basic and clinical science arenas because of the growing body of clinical trials' data showing that exclusion of immune cells from the CNS only modestly slows disease progression to disability. Accordingly, there is significant need for expanding the scope of potential disease mechanisms to understand the etiology of MS. Concomitantly, the use of a broader range of pre-clinical animal models for characterizing existing efficacious clinical treatments may elucidate additional or unexpected mechanisms of action for these drugs that augment insight into MS etiology.

Overexpression of CHOP in Myelinating Cells Does Not Confer a Significant Phenotype under Normal or Metabolic Stress Conditions.

Unlabelled: The PKR-like endoplasmic reticulum kinase (PERK) pathway of the unfolded protein response (UPR) is protective against toxic accumulations of misfolded proteins in the endoplasmic reticulum, but is thought to drive cell death via the transcription factor, CHOP. However, in many cell types, CHOP is an obligate step in the PERK pathway, which frames the conundrum of a prosurvival pathway that kills cells. Our laboratory and others have previously demonstrated the prosurvival activity of the PERK pathway in oligodendrocytes.