The Protein Data Bank: unifying the archive

The Protein Data Bank (PDB; http://www.pdb.org/) is the single worldwide archive of structural data of biological macromolecules. This paper describes the progress that has been made in validating all data in the PDB archive and in releasing a uniform archive for the community. We have now produced a collection of mmCIF data files for the PDB archive (ftp://beta.rcsb.org/pub/pdb/uniformity/data/mmCIF/). A utility application that converts the mmCIF data files to the PDB format (called CIFTr) has also been released to provide support for existing software.     

Potent γ-secretase inhibitors/modulators interact with amyloid-β fibrils but do not inhibit fibrillation: A high-resolution NMR study

Recently, γ-secretase modulators (GSM) have been shown to interact directly with the amyloid precursor protein (APP) and simultaneously inhibit the activity of the Presenilin domain of γ-secretase. A clear understanding of the molecular recognition pathways by which GSM can target both γ-secretase and Aβ precursor protein can lead to the development of more effective inhibitors. To examine whether this direct interaction with APP affects the downstream Aβ fibril formation, we chose to investigate three different molecules in this study: Sulindac sulfide, Semagacestat and E2012 from the class of generation I GSMs, γ-secretase inhibitors (GSI), and generation II GSM molecules, respectively. Firstly, through NMR based ligand titration, we identified that Sulindac sulfide and Semagacestat interact strongly with Aβ40 monomers, whereas E2012 does not. Secondly, using saturation transfer difference (STD) NMR experiments, we found that all three molecules bind equally well with Aβ40 fibrils. To determine if these interactions with the monomer/fibril lead to a viable inhibition of the fibrillation process, we designed an NMR based time-dependent assay and accurately distinguished the inhibitors from the non-inhibitors within a short period of 12 h. Based on this pre-seeded fibril assay, we conclude that none of these molecules inhibit the ongoing fibrillation, rather ligands such as Semagacestat and E2012 accelerated the rate of aggregation.     

Dynamic Quality of Service Model for Improving Performance of Multimedia Real-Time Transmission in Industrial Networks

Nowadays, quality of service (QoS) is very popular in various research areas like distributed systems, multimedia real-time applications and networking. The requirements of these systems are to satisfy reliability, uptime, security constraints and throughput as well as application specific requirements. The real-time multimedia applications are commonly distributed over the network and meet various time constraints across networks without creating any intervention over control flows. In particular, video compressors make variable bit-rate streams that mismatch the constant-bit-rate channels typically provided by classical real-time protocols, severely reducing the efficiency of network utilization. Thus, it is necessary to enlarge the communication bandwidth to transfer the compressed multimedia streams using Flexible Time Triggered- Enhanced Switched Ethernet (FTT-ESE) protocol. FTT-ESE provides automation to calculate the compression level and change the bandwidth of the stream. This paper focuses on low-latency multimedia transmission over Ethernet with dynamic quality-of-service (QoS) management. This proposed framework deals with a dynamic QoS for multimedia transmission over Ethernet with FTT-ESE protocol. This paper also presents distinct QoS metrics based both on the image quality and network features. Some experiments with recorded and live video streams show the advantages of the proposed framework. To validate the solution we have designed and implemented a simulator based on the Matlab/Simulink, which is a tool to evaluate different network architecture using Simulink blocks.     

Development of antler-type fruiting bodies of Ganoderma lucidum and determination of its biochemical properties

Following the importance of antler-type fruiting bodies of Ganoderma lucidum, in this study, the impact of main growth parameters such as ventilation and light on the development of antler-type fruiting bodies has been investigated together with the determination of physico-chemical properties of antler fruiting bodies. For this, the primordia bags of G. lucidum were kept under controlled ventilation to adjust the CO₂ produced by the mushrooms owing to its respiration under light and dark conditions. The bioactive compounds such as phenolics, flavonoids, water-soluble polysaccharides and ganoderic acid showed a two-fold increase in the antler-type fruiting bodies as compared to normal kidney-shaped fruiting bodies. It is assumed from this study that the antler type fruiting bodies are developed due to restricted ventilation which causes an increase in the level of CO₂ gas in the air as a result of respiration of mushroom. The shape and colour of antler fruiting bodies again dependent on the light provided in the growth chamber. This study also proves that with the manipulation of light and ventilation antler-type fruiting bodies of G. lucidum could be developed with higher quantity of bioactive compounds and with higher antioxidant potential.     

Requirement for Shc in TCR-mediated activation of a T cell hybridoma.

Engagement of the TCR determines the fate of T cells to activate their functional programs, proliferate, or undergo apoptosis. The intracellular signal transduction pathways that dictate the specific outcome of receptor engagement have only been partially elucidated. The adapter protein, Shc, is involved in cytokine production, mitogenesis, transformation, and apoptosis in different cell systems. We found that Shc becomes phosphorylated on tyrosine residues upon stimulation of the TCR in DO11.10 hybridoma T cells; therefore, we investigated the role of Shc in activation-induced cell death in these cells by creating a series of stably transfected cell lines. Expression of Shc-SH2 (the SH2 domain of Shc) or Shc-Y239/240F (full-length Shc in which tyrosines 239 and 240 have been mutated to phenylalanine) resulted in the inhibition of activation-induced cell death and Fas ligand up-regulation after TCR cross-linking. Expression of wild-type Shc or Shc-Y317F had no significant effect. In addition, we found that Shc-SH2 and Shc-Y239/240F, but not Shc-Y317F, inhibited phosphorylation of extracellular signal-regulated protein kinase and production of IL-2 after TCR cross-linking. These results indicate an important role for Shc in the early signaling events that lead to activation-induced cell death and IL-2 production after TCR activation.     

Sea cucumbers of the Arabian Peninsula and Iran – A review of historical and current research trends

Sea cucumbers are benthic marine invertebrates with immense ecological and commercial value. Processed sea cucumbers known as “Beche-de-mer” are a delicacy in southeast Asian countries with an ever-increasing demand depleting wild stocks on a global scale. Aquaculture techniques are well developed for commercially important species (e.g. Holothuria scabra) to aid in conservation and trade. In the Arabian Peninsula and Iran, where the major land mass is surrounded by marginal seas (Arabian Gulf, Gulf of Oman, Arabian Sea, Gulf of Aden, and Red Sea), studies on sea cucumbers are rather limited and its economic value is underestimated. Historical and current research trends indicate impoverished diversity (82 species) due to environmental extremes. Artisanal fisheries exist for the sea cucumbers of Iran, Oman, and Saudi Arabia, with Yemen and United Arab Emirates (UAE) playing a key role in collection and export to Asian countries. Stock assessment and data on export indicates depletion of natural stocks in Saudi Arabia and Oman. Aquaculture trials of high value species (H. scabra) were successful in Saudi Arabia, Oman and Iran with prospects for further expansion. Research on ecotoxicological properties and bioactive substances conducted in Iran demonstrates an immense research potential. Molecular phylogeny, biology, use in bioremediation, and characterisation of bioactive compounds were identified as potential gaps in research. Expanding aquaculture operations could revive exports and recuperate damaged stocks through sea ranching. Furthermore, regional cooperation, networking, training, and capacity building could help fill the gaps in sea cucumber research, which will aid in its effective conservation and management.     

Probing the interaction of thionine with human serum albumin by multispectroscopic studies and its in vitro cytotoxic activity toward MCF-7 breast cancer cells

The studies on protein–dye interactions are important in biological process and it is regarded as vital step in rational drug design. The interaction of thionine (TH) with human serum albumin (HSA) was analyzed using isothermal titration calorimetry (ITC), spectroscopic, and molecular docking technique. The emission spectral titration of HSA with TH revealed the formation of HSA–TH complex via static quenching process. The results obtained from absorption, synchronous emission, circular dichroism, and three-dimensional (3D) emission spectral studies demonstrated that TH induces changes in the microenvironment and secondary structure of HSA. Results from ITC experiments suggested that the binding of TH dye was favored by negative enthalpy and a favorable entropy contribution. Site marker competitive binding experiments revealed that the binding site of TH was located in subdomain IIA (Sudlow site I) of HSA. Molecular docking study further substantiates that TH binds to the hydrophobic cavity of subdomain IIA (Sudlow site I) of HSA. Further, we have studied the cytotoxic activity of TH and TH–HSA complex on breast cancer cell lines (MCF-7) by MTT assay and LDH assay. These studies revealed that TH–HSA complex showed the higher level of cytotoxicity in cancer cells than TH dye-treated MCF-7 cells and the significant adverse effect did not found in the normal HBL-100 cells. Fluorescence microscopy analyses of nuclear fragmentation studies validate the significant reduction of viability of TH–HSA-treated human MCF-7 breast cancer cells through activation of apoptotic-mediated pathways.