Circumscription of Fulbrightiella gen. nov. and Sherwoodiella gen. nov., Two Novel Genera in the Calotrichaceae (Nostocales,Cyanobacteria)

Three novel strains in Calotrichaceae from tropical habitats were isolated and characterized with regard to their morphology, phylogenetic placement, and secondary structures of conserved domains in the 16S-23S internal transcribed spacer (ITS). The strains fell into two clades formerly identified as Calothrix from freshwater and brackish habitats. Based on both morphology and ecology, they differed from the type species of Calothrix, C. confervicola, which is marine, has wide trichomes with short cells, and narrows abruptly to a hyaline hair. The first clade grouped species with heteropolar filaments widened at the base and narrowed gradually toward the apex but not ending in a hair, with basal heterocytes that are formed in series as the apically placed heterocytes senesce; this clade is being named Fulbrightiella gen. nov., with two named species, F. bharadwajae sp. nov. and F. oahuensis sp. nov. The second clade was comprised of a single species with isopolar trichomes that are untapering as hormogonia, but which widen midfilament and taper toward both ends following growth. These trichomes develop pairs of heterocyte mid-filament, causing fragmentation into heteropolar trichomes with basal heterocytes and ends that taper, but not to a hair. This clade consists of a single species at present, Sherwoodiella mauiensis. With this action, four clades in the Calotrichaceae have been named: Macrochaete, Dulcicalothrix, Fulbrightiella, and Sherwoodiella. Calothrix sensu stricto is truly marine, morphologically distinct, and unsequenced; finding and sequencing the generitype for Calothrix remains as the most important and unfinished task in the revision of the Calotrichaceae.     

Modelling and Characterization of Glial Fibrillary Acidic Protein

Glial Fibrillary Acidic Protein (GFAP) is an intermediate-filament (IF) protein that maintains the astrocytes of the Central Nervous System in Human. This is differentially expressed during serological studies in inflamed condition such as Rheumatoid Arthritis (RA). Therefore, it is of interest to glean molecular insight using a model of GFAP (49.88 kDa) due to its crystallographic nonavailability. The present study has been taken into consideration to construct computational protein model using Modeller 9.11. The structural relevance of the protein was verified using Gromacs 4.5 followed by validation through PROCHECK, Verify 3D, WHAT-IF, ERRAT and PROVE for reliability. The constructed three dimensional (3D) model of GFAP protein had been scrutinized to reveal the associated functions by identifying ligand binding sites and active sites. Molecular level interaction study revealed five possible surface cavities as active sites. The model finds application in further computational analysis towards drug discovery in order to minimize the effect of inflammation.     

Histology of vitamin A induced ectopic limbs and normal hind limbs in tadpoles of Polypedates maculatus

Marked histological similarities were observed between normal and vitamin A induced ectopic limb buds of P. maculatus. However, close association of nephric tubule and lateral plate mesoderm, as seen in normal hind limb bud does not seem to be essential for ectopic limb development. The ectopic limbs tend to develop in pairs.     

Birth defects and anti-heat shock protein 70 antibodies in early pregnancy

Abstract It has been suggested that induction of the heat shock response in the mammalian embryo during the critical period of organogenesis can result in anatomical malformation. We measured serum heat shock protein 70 (Hsp70), anti-Hsp70, and anti-Hsp60 in samples taken from expectant mothers at 16 weeks gestation. Samples from women whose babies were born with a birth defect (n = 30) were compared with controls who gave birth to healthy babies (n = 46). Anti-Hsp70 levels were significantly elevated in patients who later gave birth to babies with cleft lip or palate or neurological abnormalities (n = 10): 260 (223-406) microg/mL compared to 150 (88-207) microg/mL in controls (P < 0.001). No significant differences were found in serum Hsp70 and anti-Hsp60 levels between cases and controls. This finding of increased maternal anti-Hsp70 in patients who later gave birth to babies with these abnormalities suggests a previous stressful event may have contributed to the pathogenesis. Further work is required to determine whether Hsp70 has a direct or indirect role in this pathogenesis or whether anti-Hsp70 is simply a marker of a prior increase in Hsp70 due to a physiological stress that itself resulted in the damage. This work is consistent with previous studies showing a buffering role for Hsps in evolution.     

The discovery and preclinical evaluation of BMS-707035, a potent HIV-1 integrase strand transfer inhibitor

BMS-707035 is an HIV-1 integrase strand transfer inhibitor (INSTI) discovered by systematic optimization of N-methylpyrimidinone carboxamides guided by structure-activity relationships (SARs) and the single crystal X-ray structure of compound 10. It was rationalized that the unexpectedly advantageous profiles of N-methylpyrimidinone carboxamides with a saturated C2-substitutent may be due, in part, to the geometric relationship between the C2-substituent and the pyrimidinone core. The single crystal X-ray structure of 10 provided support for this reasoning and guided the design of a spirocyclic series 12 which led to discovery of the morpholino-fused pyrimidinone series 13. Several carboxamides derived from this bicyclic scaffold displayed improved antiviral activity and pharmacokinetic profiles when compared with corresponding spirocyclic analogs. Based on the excellent antiviral activity, preclinical profiles and acceptable in vitro and in vivo toxicity profiles, 13a (BMS-707035) was selected for advancement into phase I clinical trials.     

Solventless photocurable film coating: Evaluation of drug release,mechanical strength,and photostability

A new solventless photocurable film-coating system was investigated in which nonpareil beads were coated in a minicoating pan with liquid prepolymer (L) and powdered solid pore-forming agents (S) and cured by UV light. Release from the coating could by altered by changing the material, the number of layers, and the coating thickness. Immediate release of a blue dye contained in the nonpareils was obtained with sodium starch glycolate as a pore former that swelled the coating and yielded large pores; through these pores the dye quickly released while leaving behind the scaffold provided by the photocured prepolymer. Simple pore formers (lactose and sodium chloride) dissolved away without swelling and provided a more sustained release. The nature of the scaffold and pore structure of the coating were determined by simultaneously monitoring the release of sodium chloride from the coating and blue dye from the beads. At least 50% of the sodium chloride that was incorporated into the coating released before the dye released through the coating, except at an S/L ratio (ratio of the amount of solid pore-forming agent to the volume of liquid prepolymer) of 2.4, where 40% of the sodium chloride was released before the release of dye. The coupling between dye release and pore formation was found to be dependent on the S/L ratio of the coating. Simulation based on percolation theory showed that the coupling of pore formation and dye release was higher when the variance in tortuosity was lower. The coating was photostable and could withstand normal handling stress. Published: July 13, 2007     

Dynamic light scattering study of peanut agglutinin: Size, shape and urea denaturation

Peanut agglutinin (PNA) is a homotetrameric protein with a unique open quaternary structure. PNA shows non-two state profile in chaotrope induced denaturation. It passes through a monomeric molten globule like state before complete denaturation (Reddyet al 1999). This denaturation profile is associated with the change in hydrodynamic radius of the native protein. Though the molten globule-like state is monomeric in nature it expands in size due to partial denaturation. The size and shape of the native PNA as well as the change in hydrodynamic radius of the protein during denaturation has been studied by dynamic light scattering (DLS). The generation of two species is evident from the profile of hydrodynamic radii. This study also reveals the extent of compactness of the intermediate state.     

Thermodynamic analysis of three state denaturation of Peanut Agglutinin

Peanut Agglutinin (PNA) is a homotetrameric protein with a very unusual open quaternary structure. During denaturation, it first dissociates into a molten globule like state, which subsequently undergoes complete denaturation. Urea denaturation of PNA at neutral pH has been studied by intrinsic fluorescence spectroscopy and has been fitted to a three state model, A4 <=> 4I <=> 4U, to get all the relevant thermodynamic parameters. Urea denaturation leads to continuous red shift of wavelength maxima. The molten globule like state is formed in a short range of urea concentration. Refolding of the denatured PNA has been attempted by intrinsic fluorescence study. Refolding by instantaneous dilution shows the occurrence of the formation of an intermediate at a relatively rapid rate, within few seconds. The transition from PNA tetramer to molten globule like state is found to have a DeltaG value of approximately 33 kcal/mole while it is approximately 8 kcal/mole for the transition from molten globule like state to a completely denatured state. This in turn indicates that the tetramerization in PNA contributes significantly to the stability of the oligomer.