Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women

Small molecular weight calcium salts, if absorbed intact, could provide a nutritional source of calcium in subjects with impaired absorption of calcium by the saturable pathway. An understanding of the mechanism of absorption of calcium oxalate (as a representative salt) may be important nutritionally and therapeutically. The aim of the present study was to develop models to study absorption, distribution and retention of calcium and oxalate in rats as a basis for studying calcium oxalate absorption. Labeled compounds (45Ca and [14C]-oxalic acid) were administered to separate groups of rats orally (n = 8-11) or intravenously (n = 3-5) and blood was sampled for up to 240 min. Data were analyzed using SAAM/CONSAM. Calcium kinetics were fitted by a model with three compartments in the body and one absorption pathway from the intestine. By contrast, oxalic acid kinetics were fitted by two pools in the body and two absorption pathways from the intestine. Calcium and oxalic acid, therefore, demonstrate different absorption and distribution kinetics in rats.     

Infection and immunity mediated by the carbohydrate recognition domain of the Entamoeba histolytica Gal/GalNAc lectin

Entamoeba histolytica causes invasive amebiasis, a major parasitic disease of the developing world, whose primary symptoms are liver abscess and colitis. All strains of E. histolytica express a 260-kDa surface Gal/GalNAc lectin that is antigenically conserved and immunogenic. The lectin is required for adherence to human intestinal epithelial cells and contact-dependent killing of immune effector cells. By expression cloning, the carbohydrate recognition domain (CRD) was identified within the lectin heavy-subunit cysteine-rich region. Of interest for a hepatic parasite, the CRD had sequence identity to the receptor-binding domain of hepatocyte growth factor (HGF) and competed with HGF for binding to the c-Met HGF receptor. In an animal model of invasive disease, immunization with the CRD inhibited liver-abscess formation, yet in humans, a naturally acquired immune response against the CRD did not persist.     

Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances

Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects including fiber hypotrophy and organelle mispositioning. The main CNM forms are caused by mutations in: the MTM1 gene encoding the phosphoinositide phosphatase myotubularin (myotubular myopathy), the DNM2 gene encoding the mechanoenzyme dynamin 2, the BIN1 gene encoding the membrane curvature sensing amphiphysin 2, and the RYR1 gene encoding the skeletal muscle calcium release channel/ryanodine receptor. MTM1, BIN1, and DNM2 proteins are involved in membrane remodeling and trafficking, while RyR1 directly regulates excitation-contraction coupling (ECC). Several CNM animal models have been generated or identified, which confirm shared pathological anomalies in T-tubule remodeling, ECC, organelle mispositioning, protein homeostasis, neuromuscular junction, and muscle regeneration. Dynamin 2 plays a crucial role in CNM physiopathology and has been validated as a common therapeutic target for three CNM forms. Indeed, the promising results in preclinical models set up the basis for ongoing clinical trials. Another two clinical trials to treat myotubular myopathy by MTM1 gene therapy or tamoxifen repurposing are also ongoing. Here, we review the contribution of the different CNM models to understanding physiopathology and therapy development with a focus on the commonly dysregulated pathways and current therapeutic targets.     

Interactions of phenol and m-cresol in the insulin hexamer, and their effect on the association properties of B28 pro --> Asp insulin analogues

Insulin's natural tendency to form dimers and hexamers is significantly reduced in a mutant insulin B28 Pro --> Asp, which has been designed as a monomeric, rapid-acting hormone for therapeutic purposes. This molecule can be induced to form zinc hexamers in the presence of small phenolic derivatives which are routinely used as antimicrobial agents in insulin preparations. Two structures of B28 Asp insulin have been determined from crystals grown in the presence of phenol and m-cresol. In these crystals, insulin exists as R6 zinc hexamers containing a number of phenol or m-cresol molecules associated with aromatic side chains at the dimer-dimer interfaces. At the monomer-monomer interfaces, the B28 Pro --> Asp mutation leads to increased conformational flexibility in the B chain C termini, resulting in the loss of important intermolecular van der Waals contacts, thus explaining the monomeric character of B28 Asp insulin. The structure of a cross-linked derivative of B28 Asp insulin, containing an Ala-Lys dipeptide linker between residues B30 Ala and A1 Gly, has also determined. This forms an R6 zinc hexamer containing several m-cresol molecules. Of particular interest in this structure are two m-cresol molecules whose binding disrupted the beta-strand in one of the dimers. This observation suggests that the cross-link introduces mechanical strain on the B chain C terminus, thereby weakening the monomer-monomer interactions.     

Spatial Planning and High-Speed Broadband: Australia's National Broadband Network and Metropolitan Planning

The Australian government is constructing a National Broadband Network (NBN), which at an estimated cost of $43 billion will be Australia's largest ever infrastructure project. The NBN, if its full benefits are to be realized, raises a number of important, but largely unexplored, questions for planning. This paper investigates the implications of the NBN for Australian metropolitan planning focusing on the question of how these plans will exploit the NBN to improve urban outcomes. The paper examines the Sydney, Melbourne and Brisbane metropolitan areas and analyses the strategies shaping the future of these regions during the rollout and implementation of the NBN. This comparative analysis reveals similarities across these three metropolitan areas in their weak stance towards the NBN. Some key findings include: (1) a segregation of infrastructure planning and metropolitan planning; (2) a lack of consistency between different policies within each metropolitan area and (3) policy gaps regarding the role of telecommunications at the metropolitan level. Considering the number of governments worldwide that are making large investments in high-speed broadband, this paper addresses policy issues that will impact upon metropolitan planning well beyond the borders of Australia.     

Facilitative effect of preexposure on heart-rate conditioning to an olfactory cue in Atlantic salmon (Salmo salar).

To examine the general principle of latent inhibition in the olfactory modality of Atlantic salmon (Salmo salar), we measured levels of heart-rate conditioning after a nonreinforced exposure to L-cysteine during the postsmoltification period for smolts and desmolts (juvenile salmon retained in freshwater). Odor preexposure occurred after the sensitive period for olfactory imprinting. A context-related hypothesis predicted that latent inhibition would retard conditioning in both smolts and desmolts. However, preexposure to L-cysteine facilitated the acquisition of the conditioned response in both groups as compared with nonexposed fish. This suggests that the capacity of juvenile salmon to learn and store odor information persists beyond the sensitive period of olfactory imprinting. Heart-rate reduction was also more accentuated in smolts than in desmolts and may possibly be related to greater activity of the thyroid gland in smolts. (PsycINFO Database Record (c) 2010 APA, all rights reserved)