TGF-β1 induction of the adenine nucleotide translocator 1 in astrocytes occurs through Smads and Sp1 transcription factors

Background  

The adenine nucleotide translocator 1 (Ant1) is an inner mitochondrial membrane protein involved with energy mobilization during oxidative phosphorylation. We recently showed that rodent Ant1 is upregulated by transforming growth factor-beta (TGF-β) in reactive astrocytes following CNS injury. In the present study, we describe the molecular mechanisms by which TGF-β1 regulates Ant1 gene expression in cultured primary rodent astrocytes.     

Nicotinamide-independent asymmetric bioreduction of CC-bonds via disproportionation of enones catalyzed by enoate reductases

The asymmetric bioreduction of activated CC-bonds catalyzed by a single flavoprotein was achieved via direct hydrogen transfer from a sacrificial 2-enone or 1,4-dione as hydrogen donor without requirement of a nicotinamide cofactor. Due to its simplicity, this system has clear advantages over conventional FAD-recycling systems.     

Biocompatible functionalisation of starch

The enzyme catalysed esterification of starch and fatty acids with terminal triple bonds is described. This material can be used as an acceptor for azide containing molecules, through azide/alkyne cycloaddition. The potential is illustrated by the production of fluorescently-labelled starch, and a biotinylated derivative which can bind streptavidin.     

Nicotinamide-independent asymmetric bioreduction of CC-bonds via disproportionation of enones catalyzed by enoate reductases

The asymmetric bioreduction of activated CC-bonds catalyzed by a single flavoprotein was achieved via direct hydrogen transfer from a sacrificial 2-enone or 1,4-dione as hydrogen donor without requirement of a nicotinamide cofactor. Due to its simplicity, this system has clear advantages over conventional FAD-recycling systems.     

Pharmacokinetic parameters as a potential predictor of response to pharmacotherapy in benign prostatic hyperplasia: a preclinical trial using dynamic contrast-enhanced MRI

We sought to assess the possibility of using pharmacokinetic parameters as a predictor of response to benign prostatic hyperplasia (BPH) pharmacotherapy via a randomized, placebo-controlled, animal preclinical trial using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Twelve male beagles with BPH were enrolled in a preclinical experimental drug trial and divided into two randomized groups with six beagles each: one drug (finasteride) group and one placebo (control) group. Two baseline MRI examinations and three follow-ups during treatment were performed on a clinical 1.5-T MRI system using axial T1- and T2-weighted magnetic resonance images for prostate volume measurement and DCE-MRI for the assessment of prostate microcirculation. A total of 0.2 mmol/kg body weight of the Gd-based contrast agent was administered with an injection rate of 0.2 ml/s. The pharmacokinetic parameters, maximum enhancement ratio (MER), transfer constant and rate constant, were assessed to characterize the microcirculation in the parenchymal zone. The time-signal intensity curve from the external iliac artery was used as the arterial input function. The correlation between baseline evaluations (prostate volume and pharmacokinetic parameters) and therapy-induced prostate volume changes under finasteride treatment were assessed. The changes in prostate volume at the end of the trial exhibited a significant linear correlation to the initial parenchymal MER (P < .02) in the finasteride group. Larger prostate volume reductions coincided with smaller initial parenchymal MER. These findings show considerable promise of using parenchymal MER as a predictor of response to BPH pharmacotherapy with finasteride.     

Rapid glycoconjugation with glycosyl amines

Conjugation of unprotected carbohydrates to surfaces or probes by chemoselective ligation reactions is indispensable for the elucidation of their numerous biological functions. In particular, the reaction with oxyamines leading to the formation of carbohydrate oximes which are in equilibrium with cyclic N-glycosides (oxyamine ligation) has an enormous impact in the field. Although highly chemoselective, the reaction is rather slow. Here, we report that the oxyamine ligation is significantly accelerated without the need for a catalyst when starting with glycosyl amines. Reaction rates are increased up to 500-fold compared to the reaction of the reducing carbohydrate. For comparison, aniline-catalyzed oxyamine ligation is only increased 3.8-fold under the same conditions. Glycosyl amines from mono- and oligosaccharides are easily accessible from reducing carbohydrates via the corresponding azides by using Shoda''s reagent (2-chloro-1,3-dimethylimidazolinium chloride, DMC) and subsequent reduction. Furthermore, glycosyl amines are readily obtained by enzymatic release from N-glycoproteins making the method suited for glycomic analysis of these glycoconjugates which we demonstrate employing RNase B. Oxyamine ligation of glycosyl amines can be carried out at close to neutral conditions which makes the procedure especially valuable for acid-sensitive oligosaccharides.

A new method for carbohydrate-oxyamine ligation starting from glycosyl amines 1 instead of the commonly used reducing sugars 2 results in tremendously increased ligation rates without the need for a catalyst, such as aniline.