Imidazopyridyl compounds as aldosterone synthase inhibitors

The inhibition of aldosterone synthase (CYP11B2) may be an effective treatment of hypertension and heart failure, among other ailments. Previously reported benzimidazole CYP11B2 inhibitors led the way for bioisosteric imidazopyridines that are both potent and selective over CYP11B1.     

G protein-coupled receptor activation: analysis of a highly constrained, "straitjacketed" rhodopsin

G protein-coupled receptor (GPCR) activation is generally assumed to result in a significant structural rearrangement of the receptor, presumably involving the rigid body movement of transmembrane helices. We have investigated the activation of the GPCR rhodopsin by the construction and analysis of a mutant which contains a total of four disulfide bonds connecting the cytoplasmic ends of helices 1 and 7, and 3 and 5, and the extracellular ends of helices 3 and 4, and 5 and 6. Despite the constraints imposed by four disulfides, this "straitjacketed" receptor retains the ability to activate the G protein transducin and, therefore, provides insight into the molecular mechanism of the initial step in signal transduction of this important class of receptors.     

ACUTE EFFECTS OF MOVEMENT VELOCITY ON BLOOD LACTATE AND GROWTH HORMONE RESPONSES AFTER ECCENTRIC BENCH PRESS EXERCISE IN RESISTANCE-TRAINED MEN

This study aimed to compare the effects of different velocities of eccentric muscle actions on acute blood lactate and serum growth hormone (GH) concentrations following free weight bench press exercises performed by resistance-trained men. Sixteen healthy men were divided into two groups: slow eccentric velocity (SEV; n = 8) and fast eccentric velocity (FEV; n = 8). Both groups performed four sets of eight eccentric repetitions at an intensity of 70% of their one repetition maximum eccentric (1RMecc) test, with 2-minute rest intervals between sets. The eccentric velocity was controlled to 3 seconds per range of motion for SEV and 0.5 seconds for the FEV group. There was a significant difference (P < 0.001) in the kinetics of blood lactate removal (at 3, 6, 9, 15, and 20 min) and higher mean values for peak blood lactate (P = 0.001) for the SEV group (9.1 ± 0.5 mM) compared to the FEV group (6.1 ± 0.4 mM). Additionally, serum GH concentrations were significantly higher (P < 0.001) at 15 minutes after bench press exercise in the SEV group (1.7 ± 0.6 ng · mL⁻¹) relative to the FEV group (0.1 ± 0.0 ng · mL⁻¹). In conclusion, the velocity of eccentric muscle action influences acute responses following bench press exercises performed by resistance-trained men using a slow velocity resulting in a greater metabolic stress and hormone response.     

Character state‐based taxa erected to accommodate fossil and extant needle stoneflies (Leuctridae – Leuctrida tax.n.) and close relatives

In order to accommodate a newly discovered fossil specimen related to a subset of extant needle stoneflies (Leuctridae sensu Zwick, 2000), we provide a comparative analysis of the wing venation of these insects, and of their close relatives, primarily based on extant material. A number of character states potentially supporting monophyletic taxa are identified, and are used to erect taxon names under the cladotypic nomenclatural procedure. We introduce a new standard definition in which the mention of the antonym of the defining character state is applied. The proposed taxa, and taxa inclusiveness, are as follows: Nemouromorpha > Capniida/Leuctrida/‘Nemouridae s.l.’, and Leuctrida > Exeleuctrida > Mioleuctrida & Eleuctrida > Collaleuctrida. This scheme allowed us to tentatively accommodate several fossil species described earlier and the new specimen, left undetermined at the genus and species levels, but assigned to Collaleuctrida. To optimize retrieval of hierarchical information, we introduce the use of ‘nec’ (Latin for ‘but not’) into the taxonomic address to indicate exclusion from a taxon. For example, Mioleuctrida nec Collaleuctrida ?yehae indicates that ?yehae can be assigned to Mioleuctrida but can also be conclusively excluded from Collaleuctrida. Based on the investigated case, it is finally argued that the cladotypic nomenclatural procedure is optimal regarding name use and numbers, and allows adequate treatment of homoplasy.