Olfactory Receptor Database: a database of the largest eukaryotic gene family.

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that stores data on Olfactory Receptor-like molecules (ORs) and has been open to the public since June 1996. It contains a public and a private area. The public area includes published DNA and protein sequence data for ORs, links to OR models and data on their expression, chromosomal localization and source organism, as well as (i) links to bibliography through PubMed and (ii) interactive WWW-based tools, such as BLAST homology searching. The private area functions as a service to laboratories that are actively cloning receptors. Source laboratories enter the sequences of the receptor clones they have characterized to the private database and can search for identical or near identical OR sequences in both public and private databases. If another laboratory has cloned and deposited an identical or closely matching sequence there are means for communication between the laboratories to help avoid duplication of work. ORDB is available via the WWW at http://crepe.med.yale.edu/ORDB/HTML     

Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.     

Pretesting static and dynamic stretching does not affect maximal strength

The purpose of this study was to determine whether there was a significant difference in static stretching (SS), dynamic stretching (DS), and no stretching (NS) on maximal strength (one-repetition maximum [1RM]) in the bench and leg presses using free weights on 19 college-aged men and 32 women. Most of the participants were moderately to very active and had previous experience with weight training. The design was repeated measures, with each treatment being randomly assigned. Each testing session was separated by 72 hours. Moderate-intensity stretching was defined as stretching as far as possible without any assistance, and subjects were encouraged to do their best. For the SS routine, the chest, shoulder, triceps, quadriceps, and hamstrings were stretched. Three repetitions were performed for 15 seconds, each separated by a 10-second rest. For DS, the upper-body stretch was swinging each arm, one at a time, as far forward and then as far backward as possible in a diagonal plane. For the legs, the same movement was done for each leg, except performed in a sagittal plane. Each forward and backward movement took about 2 seconds. Three 30-second sets were administered, and a 10-second rest was allowed between sets. Next, 1RM was determined for the bench and leg presses in random order. Two warm-up sets were given, followed by several 1RM attempts. The last successful lift was recorded as the 1RM. Data were reported using means +/- SD. A one-way ANOVA with repeated measures was used with alpha set at 0.05. There was no significant difference among the treatments. Moderate-intensity stretching does not seem to adversely affect 1RM in the bench and leg presses.     

Evaluation of novel hyphodermin derivatives as glycogen phosphorylase a inhibitors

The lipophilicity, permeability, solubility, polar surface area and 'rule-of-five' properties were assessed, using QikProp v2.5 (Schr?dinger, Inc.) and ALOGPS 2.1 calculations, for 25 Hyphodermin derivatives. These compounds obeyed the 'rule-of-five', and the calculated physicochemical values were generally within desired limits. All compounds were tested against Glycogen Phosphorylase a (GPa). Four phenyl and benzyl substituted 2-oxo-hexahydro and tetrahydrobenzo[cd]indole carboxylic acids were identified as novel inhibitors of GPa with estimated IC(50) values in the range 0.8-1.3mM. Molecular modelling of these novel inhibitors was used to obtain the main structural features of this class of molecule for future structure-activity relationship studies.     

The discovery of novel calcium sensing receptor negative allosteric modulators

The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.     

Glycogen phosphorylase inhibitory effects of 2-oxo-1,2-dihydropyridin-3-yl amide derivatives

Glycogen phosphorylase (GP) plays a crucial role in the conversion of glycogen to glucose-1-phosphate (and in turn glucose) and is a promising target for therapeutic intervention in diabetes. In this study we synthesized new derivatives of 2-oxo-1,2-dihydropyridin-3-yl amides using a facile aminolysis reaction, in which different alkyl and aryl esters and amides are substituted at N-1 and C-3 of the heterocyclic ring. The in vitro inhibitory activity of compounds against glycogen phosphorylase was evaluated. From this series the most potent compound exhibits good GPa inhibition (IC₅₀ = 6.3 μM). A preliminary study of these compounds showed that anti-GP activity was decreased by the incorporation of a C3–N carbonyl group and favored by increased lipophilicity.     

Restoring depleted coral‐reef fish populations through recruitment enhancement: a proof of concept

To determine whether enhancing the survival of new recruits is a sensible target for the restorative management of depleted coral‐reef fish populations, settlement‐stage ambon damsel fish Pomacentrus amboinensis were captured, tagged and then either released immediately onto small artificial reefs or held in aquaria for 1 week prior to release. Holding conditions were varied to determine whether they affected survival of fish: half the fish were held in bare tanks (non‐enriched) and the other half in tanks containing coral and sand (enriched). Holding fish for this short period had a significantly positive effect on survivorship relative to the settlement‐stage treatment group that were released immediately. The enrichment of holding conditions made no appreciable difference on the survival of fish once released onto the reef. It did, however, have a positive effect on the survival of fish while in captivity, thus supporting the case for the provision of simple environmental enrichment in fish husbandry. Collecting and holding settlement‐stage fish for at least a week before release appear to increase the short‐term survival of released fish; whether it is an effective method for longer‐term enhancement of locally depleted coral‐reef fish populations will require further study.     

Differences in cue use and spatial memory in men and women

Men and women differ in their ability to solve spatial problems. There are two possible proximate explanations for this: (i) men and women differ in the kind (and value) of information they use and/or (ii) their cognitive abilities differ with respect to spatial problems. Using a simple computerized task which could be solved either by choosing an object based on what it looked like, or by its location, we found that the women relied on the object's visual features to solve the task, while the men used both visual and location information. There were no differences between the sexes in memory for the visual features of the objects, but women were poorer than men at remembering the locations of objects.