In 1813 Gantzer described 2 accessory muscles in the human forearm which bear his name (Wood, 1868; Macalister, 1875; Testut, 1884; Le Double, 1897). The more frequent of the 2 accessory muscles or ‘accessorius ad pollicem’ was found to arise from the coronoid process of the ulna, coursing distally to attach into the flexor pollicis longus muscle (flexor pollicis longus accessory head, FPLah). The less frequently observed or ‘accessorius ad flexorem profundum digitorum’ was again found to arise from the coronoid process and course to join into the flexor digitorum profundus (flexor digitorum profundus accessory head, FDPah). Since their initial description, they have been examined in further detail by a number of authors (Wood, 1868; Macalister, 1875; Le Double, 1897; Dykes & Anson, 1944; Mangini, 1960; Malhotra et al. 1982; Dellon & McKinnon, 1987; Kida, 1988). These studies, most of them focusing on the FPLah, all show different results of prevalence, origin, insertion, relations and nerve supply. We undertook this study with the aim of providing a more accurate account of the detailed morphology of both accessory muscles because of the above‐mentioned inconsistent anatomical descriptions and the lack of information as to important aspects such as vascular supply, morphology (shape and length) and the coexistence of both accessory heads.
Organic chemistry Z 0200The Role of Internal Water Molecules in the Structure and Function of the Rhodopsin Family of G Protein-Coupled Receptors -[53 refs.]. -(PARDO*, L.; DEUPI, X.; DOELKER, N.; LOPEZ-RODRIGUEZ, M. L.; CAMPILLO, M.; ChemBioChem 8 (2007) 1, 19-24; Lab. Med. Comput., Fac. Med., Univ. Auton.
Among serotonin receptors (5-HTRs), the 5-HT(4) subtype is of considerable interest because it is involved in (patho)physiological processes both in peripheral and central nervous systems. In addition to the clinical use of 5-HT(4R) agonists in the treatment of gastrointestinal motility disorders, the potential use of antagonists in the treatment of irritable bowel syndrome, arrhythmias and micturition disturbances are currently under investigation. This article will review the development of the most important classes of 5-HT(4R) antagonists with an emphasis on benzimidazole derivatives, their structure-affinity relationships, ligand-receptor interactions and pharmacological applications.
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The massive amount of data generated from genome sequencing brings tons of newly identified mutations, whose pathogenic/non-pathogenic effects need to be evaluated. This has given rise to several mutation predictor tools that, in general, do not consider the specificities of the various protein groups. We aimed to develop a predictor tool dedicated to membrane proteins, under the premise that their specific structural features and environment would give different responses to mutations compared to globular proteins. For this purpose, we created TMSNP, a database that currently contains information from 2624 pathogenic and 196 705 non-pathogenic reported mutations located in the transmembrane region of membrane proteins. By computing various conservation parameters on these mutations in combination with annotations, we trained a machine-learning model able to classify mutations as pathogenic or not. TMSNP (freely available at http://lmc.uab.es/tmsnp/) improves considerably the prediction power of commonly used mutation predictors trained with globular proteins.
Background
Olfactory receptors (ORs) constitute a large family of sensory proteins that enable us to recognize a wide range of chemical volatiles in the environment. By contrast to the extensive information about human olfactory thresholds for thousands of odorants, studies of the genetic influence on olfaction are limited to a few examples. To annotate on a broad scale the impact of mutations at the structural level, here we analyzed a compendium of 119,069 natural variants in human ORs collected from the public domain.
Results
OR mutations were categorized depending on their genomic and protein contexts, as well as their frequency of occurrence in several human populations. Functional interpretation of the natural changes was estimated from the increasing knowledge of the structure and function of the G protein-coupled receptor (GPCR) family, to which ORs belong. Our analysis reveals an extraordinary diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a significant number of changes occurring at the structurally conserved regions. A particular attention is paid to mutations in positions linked to the conserved GPCR activation mechanism that could imply phenotypic variation in the olfactory perception. An interactive web application (hORMdb, Human Olfactory Receptor Mutation Database) was developed for the management and visualization of this mutational dataset.
Conclusion
We performed topological annotations and population analysis of natural variants of human olfactory receptors and provide an interactive application to explore human OR mutation data. We envisage that the utility of this information will increase as the amount of available pharmacological data for these receptors grow. This effort, together with ongoing research in the study of genetic changes in other sensory receptors could shape an emerging sensegenomics field of knowledge, which should be considered by food and cosmetic consumer product manufacturers for the benefit of the general population.
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