Nucleosides,III1 Synthesis and Properties of 2-Trifluoromethyl-Naphthimidazole-Ribonucleoside

Abstract

The fusion reaction between 2-trifluoromethylnaphth[2,3-d]imidazole (1) and 1-0-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose (2) leads to 2,3′,5′-tri-O-benzoyl-1-β-D-ribofuranosylnaphth[2,3-d]imidazole (3). Debenzoylation of (3) gives the corresponding nucleoside 1-β-D-ribofuranosyl -2-trifluoromethylnaphth[2,3-d]imidazole (4). Structural proofs are based on elementary analysis, UV-and ¹H-NMR spectra.     

Nucleosides,XL1 Synthesis and Properties of lin-Naphthamidazole-Ribonucleosides

Abstract

The fusion reaction between 1-trimethylsilyl-naphth[2,3-d]imidazole (3) and its 2-methyl derivative (4) with 2, 3, 5-tri-O-benzoyl-1-bromo-D-ribofuranose (6) leads to anomeric mixtures of the corresponding 2', 3', 5'-tri-O-benzoyl-1α- and β-D-ribofuranosylnaphth[2,3-d]imidazoles (7, 11 and 13). Separation of the anomers was achieved by chromatographical means and debenzoylation yielded the corresponding nucleosides (8, 12 and 10, 14). Structural proofs are based on elementary analysis, UV- and ¹H-NMR spectra.     

Effect of type-1 diabetes mellitus on the regulation of insulin and endothelin-1 receptors in rat hearts

This project assesses the treatment role with insulin and (or) angiotensin II receptor subtype-1 (AT1-R) blocker (ARB) on insulin receptor and endothelin-1 receptor subtype (ETA-R and ETB-R) regulation in rat hearts suffering from insulin-dependent diabetes mellitus (IDDM). Animals were divided into 6 groups: groups 1, 3, and 5 were controls consisting of normal, diabetic (streptozotocin-treated, once at 0 time), and diabetic supplemented daily with insulin, respectively, whereas groups 2, 4, and 6 were the controls treated daily with losartan. One month after enrollment, rats were sacrificed and samples of cardiac tissue were snapped frozen for immunostaining and Western blotting. Insulin receptor density was observed to be upregulated in the cardiomyocytes of diabetic animals, but downregulated with insulin supplementation alone. Cotreatment with insulin and an ARB resulted in drastic increase in insulin-receptor density in the diabetic rats. In addition, expression of ETA-R in cardiomyocytes was upregulated and was consistently maintained within the various treatment modalities. However, ETB-R expression was significantly reduced in the diabetic group treated with both insulin and an ARB. The changes in the expression of the insulin, the ETA-Rs, and the ETB-Rs at the various sites of the myocardium and the effect of both insulin treatment and blockade of the AT1-R explain the new benefits related to the halting of myocardial remodeling in IDDM rats.     

The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila

Background

Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes.

Methodology/Principal Findings

In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component.

Conclusion/Significance

We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.     

Integrated dataset of screening hits against multiple neglected disease pathogens

New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach.     

Left atrial appendage closure: outcomes and challenges

Whereas the left atrial appendage plays a rather minor role under physiological circumstances, it gains an importance in patients with atrial fibrillation. Compelling evidence has revealed that the left atrial appendage is implicated as the source of thrombus in the vast majority of strokes in atrial fibrillation. Oral anticoagulation remains the standard of care for stroke prevention in atrial fibrillation; nevertheless, this treatment has several limitations and is often contraindicated, particularly in the elderly population in whom the risk of stroke is high. Therefore, occluding the left atrial appendage is a logical approach to prevent thrombus formation and subsequent cardioembolic events in these patients. We present a review of clinical outcomes of patients with atrial fibrillation undergoing left atrial appendage closure and the challenges faced in this field.     

The seasonality of zooplanktivorous fish in an African reservoir (Gebel Aulia Reservoir,White Nile,Sudan)

The fish fauna of Gebel Aulia reservoir (White Nile) consists of 52 species withAlestes baremoze Joannis andBrycinus nurse Rüppell dominating in numbers and biomass. The seasonality and condition ofA. baremoze, A. dentex (L.) andB. nurse are described in relation to various limnological factors in the reservoir, close to the dam. The zooplankton assemblage is small-sized, consists mainly of small Cladocera and shows striking seasonality. The hydrological regime, temperature and the grazing effect of fish are the major factors influencing its development.The three species belong to a eurytopic but basically riverine fish guild. They show a seasonal cycle of abundance with high numbers at periods of water storage (October–April) and low numbers during riverine conditions. This seasonal pattern of occurrence, the size structure of the population and the maturity indices give strong evidence that no resident population is present at the study site, but upstream migrations of the immature fish occur at low water level (May–September). Return migrations of juvenile fish into the area at the dam proper take place from October until April.

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Zusammenfassung In der Fischfauna des Gebel Aulia Stausees am Weißen Nil im Sudan dominieren Arten der Gatung Alestes. Die quantitative Bedeutung und das jahreszeitliche Auftreten vonA. baremoze Joannis,A. dentex Cuvier andB. nurse Rüppell wurde im Zusammenhang mit dem saisonalen Zyklus der hydrologischen und limnologischen Bedingungen untersucht. Die Häufigkeit der Fische im Staubereich ist in der Stauphase (Oktober–April) hoch und in den Monaten, in denen kein Rückstau erfolgt (Mai–September), gering.Das saisonale Muster des Auftretens, die größenstruktur der Fischpopulation and die Maturitätsfaktoren im eigentlichen Staubereich keine seßhafte Population vorhanden ist. Die Fische unternehmen kurz vor der Geschlechtsreife anadrome Wanderungen, die Jungfische wandern katadrom.