Critical assessment of structure-based sequence alignment methods at distant relationships

Accurate sequence alignments are crucial for modelling and to provide an evolutionary picture of related proteins. It is well-known that alignments are hard to obtain during distant relationships. Three thousand and fifty-two alignments of 218 pairs of protein domain structural entries, with <40% sequence identity, belonging to different structural classes, of diverse domain sizes and length-rigid/variable domains were performed using 12 programs. Structural parameters such as root mean square deviation, secondary-structural content and equivalences were considered for critical assessment. Methods that compare fragments and permit twists and translations align well during distant relationships and length variations.     

Synthesis of novel 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitrile derivatives as antimicrobial and antioxidant agents

As a part of systematic investigation of synthesis and biological activities of indole analogues linked to various heterocyclic systems, we have synthesized new compounds viz., 2-amino-4-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-pyran-3-carbonitriles (2a–i), 4,5-diamino-6-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-8-aryl-2-oxo-2,6-dihydrodipyrano [2,3-b:3,2-e]pyridine-3-carbonitriles (3a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-ones (4a–i), 4-amino-5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-1H-pyrano[2,3-d]pyrimidin-2(5H)-thiones (5a–i), 4-(5′-subtituted 2′-phenyl-1H-indol-3′-yl)-6-aryl-1,4-dihydropyrano[2,3-c]pyrazol-3-amines (6a–i) and 5-(5′-substituted 2′-phenyl-1H-indol-3′-yl)-7-aryl-3H-pyrano[2,3-d]pyrimidin-4(5H)-ones (7a–i). Antibacterial activity results revealed that, compound 6a showed promising activity versus Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Compound 6d exhibited good activity against S. aureus, K. pneumoniae and Pseudomonas aeruginosa. Antifungal activity results indicated that, compound 4d exhibited maximum zone of inhibition against Aspergillus oryzae and Aspergillus flavus. In case of antioxidant activity, compound 4a showed promising radical scavenging activity, ferric ions (Fe³⁺) reducing antioxidant power (FRAP) and metal chelating activity.     

Design,Characterization, and <Emphasis Type="Italic">In Vivo</Emphasis> Pharmacokinetics of Tacrolimus Proliposomes

The objective of this study was to develop proliposomal formulation for a poorly bioavailable drug, tacrolimus. Proliposomes were prepared by thin film hydration method using different lipids such as hydrogenated soy phosphatidylcholine (HEPC), soy phosphatidylcholine (SPC), distearyl phosphatidylcholine (DSPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoylphosphatidylglycerol sodium (DMPG) and cholesterol in various ratios. Proliposomes were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics. In vitro drug release was carried out in purified water using USP type II dissolution apparatus. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA) and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley (SD) rats. Among the different formulations, proliposomes with drug/DSPC/cholesterol in the ratio of 1:2:0.5 demonstrated the desired particle size and zeta potential. Enhanced drug release was observed with proliposomes compared to pure tacrolimus in purified water after 1 h. Tacrolimus permeability across PAMPA and everted rat intestinal perfusion models was significantly higher with proliposomes. The optimized formulation of proliposomes indicated a significant improvement in the rate and absorption of tacrolimus. Following a single oral administration, a relative bioavailability of 193.33% was achieved compared to pure tacrolimus suspension.     

Efficient privacy-preserving anonymous authentication scheme for human predictive online education system

Cluster Computing - In recent years, online education systems (OES) are improved tremendously with the development of information communication technology. Also, OES provides the opportunity for...     

REDD1 Is Essential for Optimal T Cell Proliferation and Survival

REDD1 is a highly conserved stress response protein that is upregulated following many types of cellular stress, including hypoxia, DNA damage, energy stress, ER stress, and nutrient deprivation. Recently, REDD1 was shown to be involved in dexamethasone induced autophagy in murine thymocytes. However, we know little of REDD1’s function in mature T cells. Here we show for the first time that REDD1 is upregulated following T cell stimulation with PHA or CD3/CD28 beads. REDD1 knockout T cells exhibit a defect in proliferation and cell survival, although markers of activation appear normal. These findings demonstrate a previously unappreciated role for REDD1 in T cell function.     

HIV-1 viral genes and mitochondrial apoptosis

The mitochondrion is an organelle that regulates various cellular functions including the production of energy and programmed cell death. Aberrant mitochondrial function is often concomitant with various cytopathies and medical disorders. The mitochondrial membrane plays a key role in the induction of cellular apoptosis, and its destabilization, as triggered by both intracellular and extracellular stimuli, results in the release of proapoptotic factors into the cytosol. Not surprisingly, proteins from the human immunodeficiency virus type 1 (HIV) have been implicated in exploiting this organelle to promote the targeted depletion of key immune cells, which assists in viral evasion of the immune system and contributes to the characteristic global immunodeficiency observed during progression of disease. Here we review the mechanisms by which HIV affects the mitochondrion, and suggest that various viral-associated genes may directly regulate apoptotic cell death.     

Cycloartane type triterpenoids from the rhizomes of Polygonum bistorta

Two new compounds, 24(E)-ethylidenecycloartanone (1) and 24(E)-ethylidenecycloartan-3alpha-ol (2) were isolated from the rhizomes of Polygonum bistorta, together with seven known compounds viz., cycloartane-3,24-dione (3), 24-methylenecycloartanone (4), gamma-sitosterol (5), beta-sitosterol (6), beta-sitosterone (7), friedelin (8) and 3beta-friedelinol (9). All the cycloartane type triterpenoids, compounds 7 and 8 are reported for the first time from this plant. A combination of 1D and 2D NMR spectroscopy and MS were mainly used to elucidate the structures of the new compounds 1 and 2.