Glatiramer promotes oligodendroglial cell maturation in a cuprizone-induced demyelination model

The therapeutic potential of glatiramer acetate (GA) in Multiple Sclerosis has been apparent for many years and has been proven effective in experimental allergic encephalomyelitis, one of its animal models.     

Properties of an Inward-Facing State of LeuT: Conformational Stability and?Substrate Release

The leucine transporter (LeuT) is a bacterial homolog of the human monoamine transporters, which are important pharmaceutical targets. There are no high-resolution structures of the human transporters available; however, LeuT has been crystallized in several different conformational states. Recently, an inward-facing conformation of LeuT was solved revealing an unexpectedly large movement of transmembrane helix 1a (TM1a). We have performed molecular dynamics simulations of the mutated and wild-type transporter, with and without the cocrystallized Fab antibody fragment, to investigate the properties of this inward-facing conformation in relation to transport by LeuT within the membrane environment. In all of the simulations, local conformational changes with respect to the crystal structure are consistently observed, especially in TM1a. Umbrella sampling revealed a soft potential for TM1a tilting. Furthermore, simulations of inward-facing LeuT with Na⁺ ions and substrate bound suggest that one of the Na⁺ ion binding sites is fully disrupted. Release of alanine and the second Na⁺ ion is also observed, giving insight into the final stage of the translocation process in atomistic detail.     

Histochemistry and histoenzymology of the hydatid cyst (Echinococcus granulosus Batsch, 1786). I. The germinal membrane.

Healthy germinal membranes of hydatid cysts from lungs of human and bovine sources were dissected and isolated for histochemical and histoenzymatic research. These techniques were performed in frozen sections and pieces of the whole membrane. Enzymatic research showed that the germinal membrane presents highly differentiated metabolic areas. These areas were topographically related with the origin and insertion of brood capsules, having differentiated structures for metabolic interchange with scolices. Taking our data into account it may be suggested that this functional differentiation could be transitory and variable for all the membrane surface. The accumulation of lipids and enzymes such as simple estarase, lipase, beta-HDH, alpha-GDH and NADPH-reductase in those areas, suggests that lipids are not a simple excretory product. This distribution probably implies that lipid metabolism or its resultant products are important in development and growth of scolices. In that sense other authors' findings and hypothesis about the possible existence of an endocrine system of the parasite, are considered. This idea being demonstrated in further researches, the lipid metabolic pathways shall bring a good pharmacological approach to the interference with parasite development.     

Properties and primary structure of a thermostable l-malate dehydrogenase from Archaeoglobus fulgidus

A thermostable l-malate dehydrogenase from the hyperthermophilic sulfate-reducing archaeon Archaeoglobus fulgidus was isolated and characterized, and its gene was cloned and sequenced. The enzyme is a homodimer with a molecular mass of 70 kDa and catalyzes preferentially the reduction of oxaloacetic acid with NADH. A. fulgidus l-malate dehydrogenase was stable for 5 h at 90° C, and the half-life at 101° C was 80 min. Thus, A. fulgidus l-malate dehydrogenase is the most thermostable l-malate dehydrogenase characterized to date. Addition of K₂HPO₄ (1 M) increased the thermal stability by 40%. The primary structure shows a high similarity to l-lactate dehydrogenase from Thermotoga maritima and gram-positive bacteria, and to l-malate dehydrogenase from the archaeon Haloarcula marismortui and other l-lactate-dehydrogenase-like l-malate dehydrogenases. Received: 20 November 1997 / Accepted: 28 February 1997