Accidental Organophosphate Poisoning in a Patient Due to a Bed Bug Pesticide in the United Kingdom: A Case Report.

Organophosphate (OP) compounds, developed during World War II, are a group of chemicals used as pesticides, insecticides and herbicides. As irreversible inhibitors of the enzyme acetylcholinesterase (AChE), they reduce anti-cholinesterase activity and therefore increase acetylcholine (ACh) levels at the neuromuscular junction (NMJ). Diazinon, the OP leading to the patient's symptoms in this report, is an amber-brown liquid that was once the most widely used insecticide in the United States of America.

The mechanism of allosteric regulation of calcium-independent phospholipase A by ATP and calmodulin binding to the ankyrin domain.

Group VIA calcium-independent phospholipase A (iPLA) is a member of the PLA superfamily that exhibits calcium-independent activity in contrast to the other two major types, secreted phospholipase A (sPLA) and cytosolic phospholipase A (cPLA), which both require calcium for their enzymatic activity. Adenosine triphosphate (ATP) has been reported to allosterically activate iPLA, and this has now been verified with a lipidomics-based mixed-micelle assay, but its mechanism of action has been unknown. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) was employed to identify ATP interaction peptide regions located within the ankyrin repeat domain at which ATP interacts.

NetSci: A Library for High Performance Biomolecular Simulation Network Analysis Computation.

We present the NetSci program-an open-source scientific software package designed for estimating mutual information (MI) between data sets using GPU acceleration and a k-nearest-neighbor algorithm. This approach significantly enhances calculation speed, achieving improvements of several orders of magnitude over traditional CPU-based methods, with data set size limits dictated only by available hardware. To validate NetSci, we accurately compute MI for an analytically verifiable two-dimensional Gaussian distribution and replicate the generalized correlation (GC) analysis previously conducted on the B1 domain of protein G.

Multiscale modeling shows how 2'-deoxy-ATP rescues ventricular function in heart failure.

2'-deoxy-ATP (dATP) improves cardiac function by increasing the rate of crossbridge cycling and Ca[Formula: see text] transient decay. However, the mechanisms of these effects and how therapeutic responses to dATP are achieved when dATP is only a small fraction of the total ATP pool remain poorly understood. Here, we used a multiscale computational modeling approach to analyze the mechanisms by which dATP improves ventricular function.

Dilated cardiomyopathy mutation in beta-cardiac myosin enhances actin activation of the power stroke and phosphate release.

Inherited mutations in human beta-cardiac myosin (M2β) can lead to severe forms of heart failure. The E525K mutation in M2β is associated with dilated cardiomyopathy (DCM) and was found to stabilize the interacting heads motif (IHM) and autoinhibited super-relaxed (SRX) state in dimeric heavy meromyosin. However, in monomeric M2β subfragment 1 (S1) we found that E525K enhances (threefold) the maximum steady-state actin-activated ATPase activity ( ) and decreases (eightfold) the actin concentration at which ATPase is one-half maximal ( ).