Tsc2 Is a Molecular Checkpoint Controlling Osteoblast Development and Glucose Homeostasis

Insulin signaling in osteoblasts regulates global energy balance by stimulating the production of osteocalcin, a bone-derived protein that promotes insulin production and action. To identify the signaling pathways in osteoblasts that mediate insulin''s effects on bone and energy metabolism, we examined the function of the tuberous sclerosis 2 (Tsc2) protein, a key target important in coordinating nutrient signaling. Here, we show that loss of Tsc2 in osteoblasts constitutively activates mTOR and destabilizes Irs1, causing osteoblasts to differentiate poorly and become resistant to insulin. Young Tsc2 mutant mice demonstrate hypoglycemia with increased levels of insulin and undercarboxylated osteocalcin. However, with age, Tsc2 mutants develop metabolic features similar to mice lacking the insulin receptor in the osteoblast, including peripheral adiposity, hyperglycemia, and decreased pancreatic β cell mass. These metabolic abnormalities appear to result from chronic elevations in undercarboxylated osteocalcin that lead to downregulation of the osteocalcin receptor and desensitization of the β cell to this hormone. Removal of a single mTOR allele from the Tsc2 mutant mice largely normalizes the bone and metabolic abnormalities. Together, these findings suggest that Tsc2 serves as a key checkpoint in the osteoblast that is required for proper insulin signaling and acts to ensure normal bone acquisition and energy homeostasis.     

Upstream and Downstream Processing of Lovastatin by Aspergillus terreus

The present study describes the enhanced production and purification of lovastatin by Aspergillus terreus in submerged batch fermentation. The enhancement of lovastatin production from A. terreus was attempted by random mutagenesis using ultraviolet radiations and nitrous acid. UV mutants exhibited increased efficiency for lovastatin production as compared with nitrous acid mutants. Among all the mutants developed, A. terreus UV-4 was found to be the hyper producer of lovastatin. This mutant gave 3.5-fold higher lovastatin production than the wild culture of A. terreus NRRL 265. Various cultural conditions were also optimized for hyper-producing mutant strain. 5 % glucose as carbon source, 1.5 % corn steep liquor as nitrogen source, initial pH value of 6, 120 h of incubation period, and 28 °C of incubation temperature were found as best parameters for higher lovastatin production in shake flasks. Production of lovastatin by wild and mutant strains of A. terreus was also scaled up to laboratory scale fermentor. The fermentation process was conducted at 28 °C, 200 rpm agitation, and 1vvm air flow rate without pH control. After the optimization of cultural conditions in 250 ml Erlenmeyer flasks and scaling up to laboratory scale fermentor, the mutant A. terreus UV-4 gave eightfold higher lovastatin production (3249.95 μg/ml) than its production by wild strain in shake flasks. Purification of lovastatin was carried out by solvent extraction method which yielded 977.1 mg/l of lovastatin with 98.99 % chromatographic purity and 26.76 % recovery. The crystal structure of lovastatin was determined using X-ray diffraction analysis which is first ever reported.     

Mapping QTLs for Swimming Ability Related Traits in Cyprinus carpio L.

Body height (BH), head length (HL), snout length (SL), and tail length (TL) are important traits related with swimming ability of fish. Therefore, improving these traits will increase the production which is the basic goal of aquaculture breeding. To understand the genetic basis of swimming ability related traits in Cyprinus carpio L., a high-density linkage map spanning 3,301 cM in 50 linkage groups was utilized for quantitative trait locus (QTL) mapping. Mapping family comprised 190 offspring and 627 molecular markers were genotyped with average distance of 5.6 cM. A total of 15 QTLs including four (qBH13, qBH30, qBH33, qBH48) for BH, four (qHL10, qHL18, qHL29, qHL48) for HL, three (qSL24, qSL27, qSL45) for SL, and four (qTL15, qTL17, qTL18, qTL44) for TL were detected on 13 linkage groups LG10, LG13, LG15, LG17, LG18, LG24, LG27, LG29, LG30, LG33, LG44, LG45, and LG48. Each LG consisted on single QTL except LG18 and LG48. LG18 was found with two QTLs associated with HL and TL. While LG48 was comprised, the QTLs related with BH and HL. The phenotype variance was recorded from 12.6 to 40.6 %. Five QTLs, qHL48, qSL45, qTL15, qTL18, and qTL44, explained phenotype variance of >20 % with a significant levels of 0.047, 0.049, 0.037, 0.025, and 0.023, respectively. The neighbored loci of these QTLs were considered as main region of chromosomes controlling the traits. These identified genetic regions will be the main source of discovering gene(s) associated with swimming ability related traits in C. carpio L.     

Sequencing and Utilization of the Gossypium Genomes

Revealing the genetic underpinnings of cotton productivity will require understanding both the prehistoric evolution of spinnable fibers, and the results of independent domestication processes in both the Old and New Worlds. Progress toward a reference sequence for the smallest Gossypium genome is a logical stepping-stone toward revealing diversity in the remaining seven genomes (A, B, C, E, F, G, K) that permitted Gossypium species to adapt to a wide range of ecosystems in warmer arid regions of the world, and toward identifying the emergent properties that account for the superior productivity and quality of tetraploid cottons. The greatest challenge facing the cotton community is not genome sequencing per se but the conversion of sequence to knowledge.     

Differences in the BAL proteome after <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> infection in wild type and SP-A-/- mice

Background  

Surfactant protein-A (SP-A) has been shown to play a variety of roles related to lung host defense function. Mice lacking SP-A are more susceptible to infection than wild type C57BL/6 mice. We studied bronchoalveolar lavage (BAL) protein expression in wild type and SP-A-/- mice infected with Klebsiella pneumoniae by 2D-DIGE.     

A bioconvection model for viscoelastic nanofluid confined by tapered asymmetric channel: implicit finite difference simulations

As part of the growing evolution in nanotechnology and thermal sciences, nanoparticles are considered as an alternative solution for the energy depletion due to their ultra-high thermal effectives. Nanofluids reflect inclusive and broad-spectrum significances in engineering, industrial and bio-engineering like power plants, energy source, air conditioning systems, surface coatings, evaporators, power consumptions, nano-medicine, cancer treatment, etc. The present study describes the bio-convective peristaltic flow of a third-grade nanofluid in a tapered asymmetric channel. Basic conservation laws of mass, momentum, energy, and concentration as well as the microorganism diffusion equation are utilized to model the problem. The simplified form of the modeled expressions is accounted with long wavelength assumptions. For solving the resulting coupled and nonlinear equations, a well-known numerical method implicit finite difference scheme has been utilized. The graphical results describe the velocity, temperature and concentration profiles, and the density of motile microorganisms at the nanoscale. Furthermore, microorganism concentration lines are analyzed.

     

Antioxidant phenylpropanoid glycosides from Buddleja davidii

Phytochemical investigations on the n-BuOH-soluble fraction of the whole plant of Buddleja davidii led to the isolation of the phenylpropanoid glycosides 1-10. Their structures were determined by 1D and 2D NMR spectroscopic techniques. All the compounds showed potent antioxidative activity in three different tests, with IC₅₀ values in the range 4.15-9.47 μM in the hydroxyl radical (˙OH) inhibitory activity test, 40.32-81.15 μM in the total ROS (reactive oxygen species) inhibitory activity test, and 2.26-7.79 μM in the peroxynitrite (ONOO^?) scavenging activity test. Calceolarioside A (1) displayed the strongest scavenging potential with IC₅₀ values of (4.15?±?0.07, 40.32?± 0.09, 2.26?±?0.03μM) for ˙OH, total ROS and scavenging of ONOO^?, respectively.     

Urease and Serine Protease inhibitory alkaloids from Isatis tinctoria

Phytochemical investigations on the alkaloidal fraction of the whole plant of the Isatis tinctoria led to the isolation of the alkaloids 1-6., 3′-Hydroxyepiglucoisatisin (3), Epiglucoisatisin (2) were found to be potent urease inhibitors in a concentration-dependent manner with IC₅₀ values 25.63 ± 0.74, 37.01 ± 0.41 and 31.72 ± 0.93, 47.33 ± 0.31 μM against Bacillus pasteurii & Jack bean urease, respectively. Compounds 3 and 2 also showed potent inhibitory potential against α-chymotrypsin with IC₅₀ values of 23.40 ± 0.21 and 27.45 ± 0.23 μM, respectively.