Publications by authors named "O E Clarke"
The glycoprotein hormones of humans, produced in the pituitary and acting through receptors in the gonads to support reproduction and in the thyroid gland for metabolism, have co-evolved from invertebrate counterparts . These hormones are heterodimeric cystine-knot proteins; and their receptors bind the cognate hormone at an extracellular domain and transmit the signal of this binding through a transmembrane domain that interacts with a heterotrimeric G protein. Structures determined for the human receptors as isolated for cryogenic electron microscopy (cryo-EM) are all monomeric despite compelling evidence for their functioning as dimers .
View Article and Find Full Text PDFIt is now possible to generate large volumes of high-quality images of biomolecules at near-atomic resolution and in near-native states using cryogenic electron microscopy/electron tomography (Cryo-EM/ET). However, the precise annotation of structures like filaments and membranes remains a major barrier towards applying these methods in high-throughput. To address this, we present TARDIS (ransformer-bsed apid imensionless nstance egmentation), a machine-learning framework for fast and accurate annotation of micrographs and tomograms.
View Article and Find Full Text PDFArticle Synopsis
- Malignant hyperthermia (MH) is a serious genetic condition triggered by certain anesthetics, particularly affecting a protein called RyR1.
- Dantrolene is the main treatment for MH, but how it works and where it binds on RyR1 was previously unclear.
- This study used cryo-electron microscopy to detail how dantrolene and another agent bind to RyR1, revealing that dantrolene's binding requires ATP or ADP and can close the channel, highlighting its potential role in sensing energy levels in cells.
Upon stimulation of membrane receptors, nicotinic acid adenine dinucleotide phosphate (NAADP) is formed as second messenger within seconds and evokes Ca signaling in many different cell types. Here, to directly stimulate NAADP signaling, MASTER-NAADP, a Membrane permeAble, STabilized, bio-rEversibly pRotected precursor of NAADP is synthesized and release of its active NAADP mimetic, benzoic acid C-nucleoside, 2'-phospho-3'F-adenosine-diphosphate, by esterase digestion is confirmed. In the presence of NAADP receptor HN1L/JPT2 (hematological and neurological expressed 1-like protein, HN1L, also known as Jupiter microtubule-associated homolog 2, JPT2), this active NAADP mimetic releases Ca and increases the open probability of type 1 ryanodine receptor.
View Article and Find Full Text PDFAims: The aim is to investigate the effect of alvimopan on postoperative ileus and length of hospital stay in patients undergoing bowel resection.
Methods: The PRISMA statement standards were followed to conduct a systematic review and meta-analysis. The available literature was searched to identify all studies comparing alvimopan with no alvimopan in patients undergoing bowel resection.