Substituting dietary linoleic acid with alpha-linolenic acid improves insulin sensitivity in sucrose fed rats

This study describes the effect of substituting dietary linoleic acid (18:2 n-6) with alpha-linolenic acid (18:3 n-3) on sucrose-induced insulin resistance (IR). Wistar NIN male weanling rats were fed casein based diet containing 22 energy percent (en%) fat with approximately 6, 9 and 7 en% saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) respectively for 3 months. IR was induced by replacing starch (ST) with sucrose (SU). Blends of groundnut, palmolein, and linseed oil in different proportions furnished the following levels of 18:3 n-3 (g/100 g diet) and 18:2 n-6/18:3 n-3 ratios respectively: ST-220 (0.014, 220), SU-220 (0.014, 220), SU-50 (0.06, 50), SU-10 (0.27, 10) and SU-2 (1.1, 2). The results showed IR in the sucrose fed group (SU-220) as evidenced by increase in fasting plasma insulin and area under the curve (AUC) of insulin in response to oral glucose load. In SU-220, the increase in adipocyte plasma membrane cholesterol/phospholipid ratio was associated with a decrease in fluidity, insulin stimulated glucose transport, antilipolytic effect of insulin and increase in basal and norepinephrine stimulated lipolysis in adipocytes. In SU-50, sucrose induced alterations in adipocyte lipolysis and antilipolysis were normalized. However, in SU-2, partial corrections in plasma insulin, AUC of insulin and adipocyte insulin stimulated glucose transport were observed. Further, plasma triglycerides and cholesterol decreased in SU-2. In diaphragm phospholipids, the observed dose dependent increase in long chain (LC) n-3 PUFA was associated with a decrease in LC-n-6 PUFA but insulin stimulated glucose transport increased only in SU-2. Thus, this study shows that the substitution of one-third of dietary 18:2 n-6 with 18:3 n-3 (SU-2) results in lowered blood lipid levels and increases peripheral insulin sensitivity, possibly due to the resulting high LCn-3 PUFA levels in target tissues of insulin action. These findings suggest a role for 18:3 n-3 in the prevention of insulin resistant states. The current recommendation to increase 18:3 n-3 intake for reducing cardiovascular risk may also be beneficial for preventing IR in humans.     

Evaluation of secondary poisoning of difethialone, a new second-generation anticoagulant rodenticide to barn owl, Tyto alba Hartert under captivity

Secondary toxcity of difethialone to Barn owl (Tyto alba) has been investigated. Difethialone was fed to owls for successive periods of 1 (phase 1), 3 (phase 2) and 6 (phase 3) days via-rodenticide dosed rats. The owls survived after the treament of rodenticide on phase 1 and phase 2 experiments but they died during phase 3 experiment. The results suggest that the difethialone could cause more secondary toxicity to owls.     

Dendrimer versus linear conjugate: Influence of polymeric architecture on the delivery and anticancer effect of paclitaxel

The relative difference in polymeric architectures of dendrimer and linear bis(poly(ethylene glycol)) (PEG) polymer in conjugation with paclitaxel has been described. Paclitaxel, a poorly soluble anticancer drug, was covalently conjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis(PEG) polymer for the potential enhancement of drug solubility and cytotoxicity. Both conjugates were characterized by 1NMR, HPLC, and MALDI/TOF. In addition, molecular conformations of dendrimer, bis(PEG), paclitaxel, and its polymeric conjugates were studied by molecular modeling. Hydrolysis of the ester bond in the conjugate was analyzed by HPLC using esterase hydrolyzing enzyme. In vitro cytotoxicity of dendrimer, bis(PEG), paclitaxel, and polymeric conjugates containing paclitaxel was evaluated using A2780 human ovarian carcinoma cells. Cytotoxicity increased by 10-fold with PAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug. Data obtained indicate that the nanosized dendritic polymer conjugates can be used with good success as anticancer drug carriers.     

Protein structure evaluation using an all-atom energy based empirical scoring function

Arriving at the native conformation of a polypeptide chain characterized by minimum most free energy is a problem of long standing interest in protein structure prediction endeavors. Owing to the computational requirements in developing free energy estimates, scoring functions--energy based or statistical--have received considerable renewed attention in recent years for distinguishing native structures of proteins from non-native like structures. Several cleverly designed decoy sets, CASP (Critical Assessment of Techniques for Protein Structure Prediction) structures and homology based internet accessible three dimensional model builders are now available for validating the scoring functions. We describe here an all-atom energy based empirical scoring function and examine its performance on a wide series of publicly available decoys. Barring two protein sequences where native structure is ranked second and seventh, native is identified as the lowest energy structure in 67 protein sequences from among 61,659 decoys belonging to 12 different decoy sets. We further illustrate a potential application of the scoring function in bracketing native-like structures of two small mixed alpha/beta globular proteins starting from sequence and secondary structural information. The scoring function has been web enabled at www.scfbio-iitd.res.in/utility/proteomics/energy.jsp.     

Developmental Studies in Porphyra Vietnamensis: a High-Temperature Resistant Species from the Indian Coast

Porphyra vietnamensis Tanaka & Pham-Hoang Ho (Bangiales, Rhodophyta) is a tropical seaweed collected from the west coast of India. Thalli of the blade phase are found growing only during the rainy season between July and September. They grow on rocky intertidal or subtidal substrata or as epiphytes on other seaweeds such as Enteromorpha flexuosa and Chaetomorpha media. The gametophytic thallus is monostromatic and covered with spines at the base. The species is monoecious. Male gametangia are found in patches that are distributed in the upper part of the thallus. Archeospores are found at the thallus margins and give rise to the blade phase after one week of germination even at 30 ^∘ C. Zygotospores germinated at 25 ^∘ C into conchocelis within three days from the date of their inoculation. Conchospores were released at 30 ^∘ C. The young blades grew at 32 ^∘ C in the laboratory.     

Bhageerath: an energy based web enabled computer software suite for limiting the search space of tertiary structures of small globular proteins

We describe here an energy based computer software suite for narrowing down the search space of tertiary structures of small globular proteins. The protocol comprises eight different computational modules that form an automated pipeline. It combines physics based potentials with biophysical filters to arrive at 10 plausible candidate structures starting from sequence and secondary structure information. The methodology has been validated here on 50 small globular proteins consisting of 2-3 helices and strands with known tertiary structures. For each of these proteins, a structure within 3-6 A RMSD (root mean square deviation) of the native has been obtained in the 10 lowest energy structures. The protocol has been web enabled and is accessible at http://www.scfbio-iitd.res.in/bhageerath.