High-resolution structure of a partially folded insulin aggregation intermediate

Insulin has long been served as a model for protein aggregation, both due to the importance of aggregation in the manufacture of insulin and because the structural biology of insulin has been extensively characterized. Despite intensive study, details about the initial triggers for aggregation have remained elusive at the molecular level. We show here that at acidic pH, the aggregation of insulin is likely initiated by a partially folded monomeric intermediate. High-resolution structures of the partially folded intermediate show that it is coarsely similar to the initial monomeric structure but differs in subtle details—the A chain helices on the receptor interface are more disordered and the B chain helix is displaced from the C-terminal A chain helix when compared to the stable monomer. The result of these movements is the creation of a hydrophobic cavity in the center of the protein that may serve as nucleation site for oligomer formation. Knowledge of this transition may aid in the engineering of insulin variants that retain the favorable pharamacokinetic properties of monomeric insulin but are more resistant to aggregation.     

In Vitro Clonal Propagation of Curcuma caesia Roxb and Curcuma zedoaria Rosc from Rhizome Bud Explants

Two species of Curcuma (C. caesia and C. zedoaria) have been propagated through tissue culture using rhizome bud explant. The best response for shoot multiplication was obtained on MS basal medium supplemented with 4 mg l^?1 BAP and 1.5 mg l^?1 NAA for C. caesia (3.5 ± 0.79 shoots per explant) and 1 mg l^?1 BAP + 0.5 mg l^?1 NAA for C. zedoaria (4.5 ± 0.15 shoots per explant). A maximum of 9.2 ± 0.15 and 8.9 ± 0.09 roots per explant were obtained for C. caesia and C. zedoaria, respectively when MS was supplemented with 0.5 mg l^?1 IAA. The rooted plants could be established in soil.     

In vitro Clonal Propagation and Organogenesis in Spilanthes acmella (L) Murray: A Herbal Pesticidal Plant of North-East India

Multiple shoots were regenerated in MS medium using different concentrations of BAP and Kn and different combinations of BAP with IAA, NAA and IBA. Highest multiplication of shoots was obtained with BAP (0.75 mg l^?1) with 28.4 shoots per explant after 60 days of culture. Shoots rooted best on IBA (0.5 mg l^?1), numbering 48.8 per explant. Organogenesis was maximum in callus cultured on MS medium supplemented with BAP (2.0 mg l^?1) and IAA (1.0 mg l^?1).     

Length–weight relationships of three small indigenous fish species from the Lower Brahmaputra,India

Length–weight relationships (LWRs) for three small indigenous fish species from the lower Brahmaputra in Assam, India: Glyptothorax telchitta, Nangra assamensis, and Gudusia chapra were studied on a monthly basis from February 2015 to January 2016. Various fishing gear types were employed: cast nets (9′ ½”), gillnets (30 × 0.9 m, 0.5″; 60 × 3 m, 1.5″) and mosquito nets (20 × 6 m, 0.04″). No previous reference is available on LWR data for two of these species.     

Length–weight relationships of two Nemacheilid fish species [Schistura fasciata Lokeshwor and Vishwanath, 2011 and Schistura reticulofasciata (Singh and Bănărescu, 1982)] from Simsang River,Meghalaya, India

Length–weight relationships (LWRs) are presented for two fish species: Schistura fasciata Lokeshwor and Vishwanath, 2011 and Schistura reticulofasciata (Singh and B?n?rescu, 1982), sampled from the Simsang River in Meghalaya, India. Fishes were caught seasonally from January to December 2015, with cast nets (10–15 mm mesh size) and electrofishing devices. The b values in the LWRs were determined as 3.09 for S. fasciata and 3.318 for S. reticulofasciata.     

Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors

Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC(50) values below micromolar range. Some of these compounds can also significantly reduce tumor growth in human tumor xenograft models in mice.     

Chemical constituents and energy content of some latex bearing plants

The latex bearing plants Plumeria alba, Calotropis procera, Euphorbia nerrifolia, Nerium indicum and Mimusops elengi were evaluated as potential renewable sources of energy and chemicals. Plant parts (leaf, stem, bark) and also whole plants were analyzed for elemental composition, oil, polyphenol, hydrocarbons, crude protein, alpha-cellulose, lignin and ash. The dry biomass yields were between 4.47 and 13.74 kg/plant. The carbon contents in whole plants varied from 38.5% to 44.9%, while hydrogen and nitrogen contents varied from 5.86% to 6.72% and 1.26% to 2.34%, respectively. The bark of the plants contained the highest amount of hydrocarbons (1.78-3.93%) and the leaves contained the lowest amounts (0.26-1.82%). The unsaponifiable materials and fatty acids in the oil fractions of whole plants ranged from 22.8% to 56.4% and 24.7% to 58.7%, respectively. The highest gross heat value was exhibited by C. procera (6145 cal/g) and the lowest by N. indicum (4405 cal/g). Hydrocarbon fractions were characterized by IR and (1)H-NMR and by thermogravimetric analyses. The activation energy (E(a)) in the third stage of decomposition was the greatest in the hydrocarbon fraction obtained from M. elengi (16.40 kJ mol(-1)) and the lowest for C. procera (3.96 kJ mol(-1)). The study indicated that the plant species might be suitable as alternative source of hydrocarbons and other phytochemicals.     

Structural basis of urea-induced unfolding of Fasciola gigantica glutathione S-transferase

Glutathione S-transferases (GSTs) are enzymes that are involved in the detoxification of harmful electrophilic endogenous and exogenous compounds by conjugating with glutathione (GSH). The liver fluke GSTs have multifunctional roles in the host–parasite interaction, such as general detoxification and bile acid sequestration to synthase activity. The GSTs have been highlighted as vaccine candidates towards parasitic flukes. In this study, we have thoroughly examined the urea-induced unfolding of a mu-class Fasciola gigantica GST1 ( FgGST1) using spectroscopic techniques and molecular dynamic simulations. FgGST1 is a highly cooperative molecule, because during urea-induced equilibrium unfolding, a concurrent unfolding of the protein without stabilization of any folded intermediate was observed. The protein was stabilized with conformational free energy of about ~12.36 kcal/mol. The protein loses its activity with increasing urea concentration, as the GSH molecule is not able to bind to the protein. We also studied the fluorescence quenching of Trp residues and the obtained K _SV data that provided additional information on the unfolding of FgGST1. Molecular dynamic trajectories simulated in different urea concentrations and temperatures indicated that urea destabilizes FgGST1 structure by weakening hydrophobic interactions and the hydrogen bond network. We observed a precise correlation between the in vitro and in silico studies.