Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation

Background

Growth factor receptor-bound protein 14 (Grb14) is an adapter protein implicated in receptor tyrosine kinase signaling. Grb14 knockout studies highlight both the positive and negative roles of Grb14 in receptor tyrosine kinase signaling, in a tissue specific manner. Retinal cells are post-mitotic tissue, and insulin receptor (IR) activation is essential for retinal neuron survival. Retinal cells express protein tyrosine phosphatase-1B (PTP1B), which dephosphorylates IR and Grb14, a pseudosubstrate inhibitor of IR. This project asks the following major question: in retinal neurons, how does the IR overcome inactivation by PTP1B and Grb14?

Results

Our previous studies suggest that ablation of Grb14 results in decreased IR activation, due to increased PTP1B activity. Our research propounds that phosphorylation in the BPS region of Grb14 inhibits PTP1B activity, thereby promoting IR activation. We propose a model in which phosphorylation of the BPS region of Grb14 is the key element in promoting IR activation, and failure to undergo phosphorylation on Grb14 leads to both PTP1B and Grb14 exerting their negative roles in IR. Consistent with this hypothesis, we found decreased phosphorylation of Grb14 in diabetic type 1 Ins2^Akita mouse retinas. Decreased retinal IR activation has previously been reported in this mouse line.

Conclusions

Our results suggest that phosphorylation status of the BPS region of Grb14 determines the positive or negative role it will play in IR signaling.

     

Analeptic agent from microbes upon cyanide degradation

Applied Microbiology and Biotechnology - Microbes being the initial form of life and ubiquitous in occurrence, they adapt to the environment quickly. The microbial metabolism undergoes alteration...     

Evaluation of the potential of cassava-based residues for biofuels production

Cassava is the third significant source of calories after rice and maize in tropical countries. The annual production of cassava crop is approximately 550 million metric tons (MMT) which generates about 350 MMT of cassava solid residues, including peel, bagasse, stem, rhizome, and leaves. Cassava peel, bagasse, stem, and rhizome can be exploited for solid, liquid and gaseous biofuels production. Biofuels production from cassava starch started in the 1970s and researchers are now extensively studying cassava residues like peel, bagasse, stem, rhizome, and leaves to unravel their applications in biofuels production. However, there are technical and economic challenges to overcome the problems existing in the production of biofuels from cassava-based residues. This review provides a comprehensive summary of the techniques used for biofuels production from various cassava-based residues.     

Screening of anti-inflammatory phytocompounds from Crateva adansonii leaf extracts and its validation by in silico modeling

Anti-inflammatory phytocompounds from Crateva adansonii DC leaf extracts were identified by GCMS analysis and its anti-inflammatory potential was evaluated by in silico molecular docking study against inflammatory molecular targets. Three different (Aqueous, Methanol and Petroleum ether) dried leaf extracts of Crateva adansonii were obtained from soxhlet extraction method. Preliminary phytoconstituents analysis of three different leaf extracts of C. adansonii confirmed the presence of various major classes of bioactive phytoconstituents such as polyphenols (tannins and flavonoids), steroids, alkaloid, coumarin, carbohydrate and terpenoids. Among three leaf extracts, methanolic leaf extract possess highest total phenolic content of 77?±?1.65?µg gallic acid equivalent (GAE)/g of dry weight of leaf extract, subsequently methanolic leaf extract also shows maximal in vitro antioxidant activity (DPPH scavenging activity) of 71.22?±?1.32% among three different leaf extracts. GC–MS analysis of petroleum ether leaf extract revealed the presence of nine phytocompounds representing 95.43% peak area percentage, among nine identified phytocompounds three phytocompounds of C. adansonii possess anti-inflammatory property namely phytol, 1-Hexyl-2-Nitrohexane and 2-Isopropyl-5-Methylcyclohexyl 3-(1-(4-Chlorophenyl)-3-Oxobutyl)-Coumarin-4-Yl Carbonate were chosen for in silico molecular docking study against four inflammatory receptor targets (COX-2, TNFα, IL-1β and IL-6) and they shows less binding energy with highest docking score ranging from ?15.9500 to 5.0869. The present study substantially indicated and proven that anti-inflammatory potential of phytocompounds from C. adansonii leaf extracts which can be exploited for commercial designing of novel anti-inflammatory drug to treat various inflammatory disorders.     

DNA Barcoding of Sharp Tail Sunfish <Emphasis Type="Italic">Masturus lanceolatus</Emphasis> Lienard, 1840 (Tetraodontiformes: Molidae)

Detailed analyses on morphometry (expressed as % standard length and % head length), meristic characters and mitochondrial barcode region sequence of the sharp tail sunfish Masturus lanceolatus Lienard, 1840 have made to confirm the species identity. Further, investigations on phylogenetic relationships between species of the Molidae family have been taken into consideration by constructing neighbor-joining tree to fulfill the gaps on taxonomical validation and their biological information.     

The PtdIns 3-Kinase/Akt Pathway Regulates Macrophage-Mediated ADCC against B Cell Lymphoma

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNγ as the effectors. Our data demonstrate that the PtdIns 3-kinase/Akt pathway is activated during macrophage-induced ADCC and that the inhibition of PtdIns 3-kinase results in the inhibition of macrophage-mediated cytotoxicity. Interestingly, downstream of PtdIns 3-kinase, expression of constitutively active Akt (Myr-Akt) in macrophages significantly enhanced their ability to mediate ADCC. Further analysis revealed that in this model, macrophage-mediated ADCC is dependent upon the release of nitric oxide (NO). However, the PtdIns 3-kinase/Akt pathway does not appear to regulate NO production. An examination of the role of the PtdIns 3-kinase/Akt pathway in regulating conjugate formation indicated that macrophages treated with an inhibitor of PtdIns 3-kinase fail to polarize the cytoskeleton at the synapse and show a significant reduction in the number of conjugates formed with tumor targets. Further, inhibition of PtdIns 3-kinase also reduced macrophage spreading on Rituximab-coated surfaces. On the other hand, Myr-Akt expressing macrophages displayed a significantly greater ability to form conjugates with tumor cells. Taken together, these findings illustrate that the PtdIns 3-kinase/Akt pathway plays a critical role in macrophage ADCC through its influence on conjugate formation between macrophages and antibody-coated tumor cells.     

Structural characterization of the bovine tracheal chondroitin sulfate chains and binding of Plasmodium falciparum-infected erythrocytes

Sequestration of Plasmodium falciparum-infected red blood cells (IRBCs) in the human placenta is mediated by chondroitin 4-sulfate (C4S). A cytoadherence assay using chondroitin sulfate proteoglycans (CSPGs) is widely used for studying C4S-IRBC interactions. Bovine tracheal chondroitin sulfate A (CSA) preparation lacking a major portion of core protein has been frequently used for the assay. Here the CSPG purified from bovine trachea and CSA were assessed for IRBC binding and the CS chains studied in detail for structure-activity relationship. The IRBCs bound at significantly higher density to the CSPG than CSA. The CS chains of CSPG/CSA are heterogeneous with varying levels of 4- and 6-sulfates, which are distributed such that approximately 80% of the 4-sulfated disaccharides are present as single and blocks of two or three separated by one to three 6-sulfated disaccharides. The remainder of the 4-sulfated disaccharides is present in blocks composed of 4-12 units, separated by 6-sulfated disaccharides. In the IRBC adherence inhibition analysis, CSA fragments with 88%-92% 4-sulfate were significantly less inhibitory than the intact CSA, indicating that the regions consisting of shorter 4-sulfated blocks efficiently bind IRBCs despite the presence of relatively high levels of 6-sulfate. This is because the 6-sulfated disaccharides have unsubstituted C-4 hydroxyls that are crucial for IRBC binding. The presence of high levels of 6-sulfate, however, significantly interfere with the IRBC binding activity of CSA, which otherwise would more efficiently bind IRBCs. Thus our study revealed the distribution pattern of 4- and 6-sulfate in bovine tracheal CSA and structural basis for IRBC binding.     

Dynamics of Metabolic Activities and Gene Expression in the Roseobacter Clade Bacterium Phaeobacter sp. Strain MED193 during Growth with Thiosulfate

Metagenomic analyses of surface seawater reveal that genes for sulfur oxidation are widespread in bacterioplankton communities. However, little is known about the metabolic processes used to exploit the energy potentially gained from inorganic sulfur oxidation in oxic seawater. We therefore studied the sox gene system containing Roseobacter clade isolate Phaeobacter sp. strain MED193 in acetate minimal medium with and without thiosulfate. The addition of thiosulfate enhanced the bacterial growth yields up to 40% in this strain. Concomitantly, soxB and soxY gene expression increased about 8-fold with thiosulfate and remained 11-fold higher than that in controls through stationary phase. At stationary phase, thiosulfate stimulated protein synthesis and anaplerotic CO₂ fixation rates up to 5- and 35-fold, respectively. Several genes involved in anaplerotic CO₂ fixation (i.e., pyruvate carboxylase, propionyl coenzyme A [CoA], and crotonyl-CoA carboxylase) were highly expressed during active growth, coinciding with high CO₂ fixation rates. The high expression of key genes in the ethylmalonyl-CoA pathway suggests that this is an important pathway for the utilization of two-carbon compounds in Phaeobacter sp. MED193. Overall, our findings imply that Roseobacter clade bacteria carrying sox genes can use their lithotrophic potential to gain additional energy from sulfur oxidation for both increasing their growth capacity and improving their long-term survival.