The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans

Choanoflagellates are the closest known relatives of metazoans. To discover potential molecular mechanisms underlying the evolution of metazoan multicellularity, we sequenced and analysed the genome of the unicellular choanoflagellate Monosiga brevicollis. The genome contains approximately 9,200 intron-rich genes, including a number that encode cell adhesion and signalling protein domains that are otherwise restricted to metazoans. Here we show that the physical linkages among protein domains often differ between M. brevicollis and metazoans, suggesting that abundant domain shuffling followed the separation of the choanoflagellate and metazoan lineages. The completion of the M. brevicollis genome allows us to reconstruct with increasing resolution the genomic changes that accompanied the origin of metazoans.     

Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease

More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models.     

Optimality Conditions and Duality for Nondifferentiable Multiobjective Semi-Infinite Programming Problems with Generalized(C,α,ρ,d)-Convexity

This paper obtains sufficient optimality conditions for a nonlinear nondifferentiable multiobjective semi-infinite programming problem involving generalized(C,α,ρ,d)-convex functions.The authors formulate Mond-Weir-type dual model for the nonlinear nondifferentiable multiobjective semiinfinite programming problem and establish weak,strong and strict converse duality theorems relating the primal and the dual problems.     

Expanding role of molecular chaperones in regulating α-synuclein misfolding; implications in Parkinson’s disease

Protein misfolding under stressful environmental conditions cause several cellular problems owing to the disturbed cellular protein homeostasis, which may further lead to neurological disorders like Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyloid lateral sclerosis and Huntington disease (HD). The presence of cellular defense mechanisms like molecular chaperones and proteasomal degradation systems prevent protein misfolding and aggregation. Molecular chaperones plays primary role in preventing protein misfolding by mediating proper native folding, unfolding and refolding of the polypeptides along with vast number of cellular functions. In past few years, the understanding of molecular chaperone mechanisms has been expanded enormously although implementation to prevent protein aggregation diseases is still deficient. We in this review evaluated major classes of molecular chaperones and their mechanisms relevant for preventing protein aggregation, specific case of α-synuclein aggregation. We also evaluate the molecular chaperone function as a novel therapeutic approach and the chaperone inhibitors or activators as small molecular drug targets.     

Synthesis of koenigicine

Summary The structure of koenigicine as 8,9-dimethoxy-3,3,5-trimethyl-3, 11-dihydropyrano-[3,2-a] carbazole (1) has been confirmed by synthesis.     

Location of quality-control stations in manufacturing systems: A simulated annealing approach

Quality is the hallmark of a competitive product. It is necessary to use inspection stations to check product quality and process performance. In this paper, we are concerned with the problem of location of inspection stations in a manufacturing system. A simulated annealing approach is developed to determine the location of inspection centers resulting in a minimum expected total cost in a multistage serial production system. The total cost includes inspection, processing, and scrapping costs at each stage of the production process. A penalty cost is also included in it to account for a defective item which is not detected by the inspection scheme. A set of test examples is solved using a simulated annealing algorithm.     

Hormetic concentrations of azadirachtin and isoesterase profiles inTribolium castaneum (Herbst) (Coleoptera: Tenebrionidae)

Electrophoretic pattern of esterases from larvae ofTribolium castaneum fed on a diet which included hormetic concentrations of azadirachtin (viz. 0.001, 0.01 and 0.1 ppm) for 10 d were studied. The results showed a dose-dependent variation in the multiple molecular forms of the esterases. The variations, however, were not limited to the synthesis of new isoforms or the deletion of existing ones; there was also variation in their relative abundance.