Protein-Protein Interactions and Muscle cell Signaling Via Syntrophin

Absence of dystrophin results in Duchenne muscular dystrophy (DMD), a lethal neuromuscular d isorder that afflicts 1 in 3500 live male births. In the sarcolemma, dystrophin is associated with a complex of proteins and glycoproteins, known as the dystrophin glycoprotein complex. The DGC constituents are dystrophin, a-dys troglycan, b-dystroglycan, syntrophin, a-sarcoglycan, b-sarcoglycan, g-sarcoglycan, d-sarcoglycan, and sarcospan. Not al l of these are single protein species. The syntrophins consists of a group of three homologous proteins composed of acidic (a) and basic (b) components. Syntrophins are known to self-associate to form oligomers. In this dissertation, syntrophin\u27s oligomerization and its interactions with the cell signaling components in vitro in skeletal muscle were investigated. Mouse a1-syntrophin sequences, produced as chimeric fusion proteins in bacteria, als o oligomerize and in a micromolar Ca2+-dependent manner. Oligomerization was localized to the N-terminal pleckstrin homology domain (PH1) or adjacent sequences; the second, C-terminal PH2 domain did not show oligomerization. PH1 was found to se lf-associate and calmodulin or Ca2+ chelating agents such as EGTA could effectively prevent this oligomerization. A single calmodulin bound per syntrophin to cause inhibition of the precipitation. Calmodulin inhibited syntrophin oligomerization in the presence or absence of Ca2+. Ca2+-binding to syntrophin is responsible for the inhibition by EGTA of syntrophin oligomerization. Syntrophins have been proposed to serve as adapter proteins. Blot overlay experiment s demonstrate that a-, b-dystroglycan, and syntrophins all bind Grb2, the growth factor receptor bound adapter protein. Mouse a1-syntrophin chimeric fusion proteins bind Grb2 in a Ca2+-independent manner. This binding was localized to two proline rich sequences near the N terminal PH1 domain. This domain is interrupted by a PDZ domain inserted nearly in middle of the PH1 domain dividing it into two parts: the N ter minal PH1 and C terminal PH1b subdomains. One proline rich sequence is Cterminal of PH1b while the other is adjacent to and overlapping with the N terminal of PH1b. Grb2 contains two SH3 domains and both contribute to binding. Intact, bacterial expressed Grb2 bound syntrophin with an apparent KD of 563 ± 15 nM. Grb2-C-SH3 domain bound syntrophin with slightly higher affinity than Grb2-N-SH3 domain. Crk-L, an SH2/SH3 protein of similar domain structure but different specificity does not bind these s yntrophin sequences. Dystrophin glycoprotein complex has been proposed to be involved in signal transduction. We have shown that laminin binding to a–dystroglycan causes syntrophin to recruit Rac1. Laminin-Sepha rose precipitates Rac1, and to a lesser extent Rho-A and Ras, from the rabbit skeletal muscle membranes in a pull-down assay. The presence of heparin, which inhibits the interaction between laminin and a–dystroglycan preven ts recruitment of Rac1. A syntrophin antibody blocks recruitment of Rac1 suggesting that the signaling pathway requires syntrophin. Sos1 is also present in the recruited complex. Jun N terminal kinase 2 is phosphorylated and activated only when laminin is attached to the dystrophin glycoprotein complex. Thus, dystrophin glycoprotein complex recruits Rac1 via syntrophin through a Grb2-Sos complex leading to activation of Jun N terminal kinase 2 only when it is attached to laminin. We postulate this signals the muscle cell to grow

Ring for test of nonlinear integrable optics

Nonlinear optics is a promising idea potentially opening the path towards achieving super high beam intensities in circular accelerators. Creation of a tune spread reaching 50% of the betatron tune would provide strong Landau damping and make the beam immune to instabilities. Recent theoretical work has identified a possible way to implement stable nonlinear optics by incorporating nonlinear focusing elements into a specially designed machine lattice. In this report we propose the design of a test accelerator for a proof-of-principle experiment. We discuss possible studies at the machine, requirements on the optics stability and sensitivity to imperfections.Comment: 3 pp. Particle Accelerator, 24th Conference (PAC'11) 28 Mar - 1 Apr 2011: New York, US

The geology and petrogenesis of the southern closepet granite

The Archaean Closepet Granite is a polyphase body intruding the Peninsular Gneiss Complex and the associated supracrustal rocks. The granite out-crop runs for nearly 500 km with an approximate width of 20 to 25 km and cut across the regional metamorphic structure passing from granulite facies in the South and green schist facies in the north. In the amphibolite-granulite facies transition zone the granite is intimately mixed with migmatites and charnockite. Field observations suggests that anatexis of Peninsular gneisses led to the formation of granite melt, and there is a space relationship between migmatite formation, charnockite development and production and emplacement of granite magma. Based on texture and cross cutting relationships four major granite phases are recognized: (1) Pyroxene bearing dark grey granite; (2) Porphyritec granite; (3) Equigranular grey granite; and (4) Equigranular pink granite. The granite is medium to coarse grained and exhibit hypidiomorphic granular to porphyritic texture. The modal composition varies from granite granodiorite to quartz monzonite. Geochemical variation of the granite suite is consistent with either fractional crystallization or partial melting, but in both the cases biotite plus feldspar must be involved as fractionating or residual phases during melting to account trace element chemistry. The trace element data has been plotted on discriminant diagrams, where majority of samples plot in volcanic arc and within plate, tectonic environments. The granite show distinct REE patterns with variable total REE content. The REE patterns and overall abundances suggests that the granite suite represents a product of partial melting of crustal source in which fractional crystallization operated in a limited number of cases

Political ideas of B.G. Tilak: colonialism, self and Hindu nationalism

De primaire focus van dit proefschrift is het onderzoeken van de politieke ideeën van BG Tilak (1856-1920), de congres-extremistische leider van de Indiase nationalistische beweging en, in het proces, de politieke en intellectuele geschiedenis van Maharashtra en India te reconstrueren tijdens de late 19e en begin 20e eeuw. Deze dissertatie daagt de oudere stijlfiguur uit die Tilak binnen de reikwijdte van de meerderheid van de hindoe-nationalistische politiek plaatst. Het plaatst zijn sociale conservatisme in de heersende sociale overtuigingen van en liturgische lezingen aangeboden door de laat 19e-eeuwse Marathi openbare intellectuelen. De belangrijkste agenda van Tilak was de creatie van een gecollectiviseerd en geradicaliseerd hindoe-zelf, geponeerd tegen het Britse kolonialisme. Zijn creatieve versmelting van moderne westerse historische exegese met Sanskriet kennissystemen in het pleiten voor hoge oudheid voor de Arische beschaving worden onderzocht. Zijn commentaar op de Bhagavad Gītā bood een infusie van ethische principes in massaal politiek activisme. Tilak slaagde erin om provinciale parochialisme ten opzichte van pan-nationale identiteiten te verminderen. Ten slotte stelt dit proefschrift dat het nationalistische ideaal van Tilak beperkt was tot Svarājya of Zelfbeschikking voor India binnen het Britse Gemenebest.Asian Studie

Characterization of eDNA from the Clinical Strain Acinetobacter baumannii AIIMS 7 and Its Role in Biofilm Formation

Release of extracellular DNA (eDNA) was observed during in vitro growth of a clinical strain of Acinetobacter baumannii. Membrane vesicles (MV) of varying diameter (20–200 nm) containing DNA were found to be released by transmission electron microscopy (TEM) and atomic force microscopy (AFM). An assessment of the characteristics of the eDNA with respect to size, digestion pattern by DNase I/restriction enzymes, and PCR-sequencing, indicates a high similarity with genomic DNA. Role of eDNA in static biofilm formed on polystyrene surface was evaluated by biofilm augmentation assay using eDNA available in different preparations, for example, whole cell lysate, cell-free supernatant, MV suspension, and purified eDNA. Biofilm augmentation was seen up to 224.64%, whereas biofilm inhibition was 59.41% after DNase I treatment: confirming that eDNA facilitates biofilm formation in A. baumannii. This is the first paper elucidating the characteristics and role of eDNA in A. baumannii biofilm, which may provide new insights into its pathogenesis

Faecal sludge treatment by vermifiltration: proof of concept

The objective of this study was to determine if composting worms and their cocoons are able to survive in and digest faecal sludge. Eighteen vermifilters with different worm and cocoon densities were set-up, fed with faecal sludge (from portable pour-flush toilets) and ran for 38 days. Samples of the sludge, effluent and vermicompost were analysed for pH, total solids, chemical oxygen demand, faecal coliforms and Ascaris spp. number and viability. Worm and vermicompost mass, and cocoon numbers were assessed at the end of this period. It was found that the composting worms survived in these conditions and cocoons hatched. The validity of the sludge analysis results are questioned in this paper and without these results only estimates of effluent treatment and solids conversion could be made. Although this study was not completely definitive it has shown that worms are capable of converting faecal sludge into vermicompost and cocoons hatch in its presence. This trial was undertaken in India

Hepaticoduodenostomy as a technique for biliary anastomosis in children with choledochal cyst: An experience with 31 cases

Objective The aim of this study was to investigate the efficacy and complications of hepaticoduodenostomy in the treatment of choledochal cyst in children. Summary background data The conventional treatment of choledochal cyst includes Roux-en-Y hepaticojejunostomy for biliary reconstruction. This procedure, however, disrupts normal bowel continuity and requires two anastomoses. We studied the technique of hepaticoduodenostomy as an effective alternative to this technique.Patients and methods A total of 31 children undergoing  hepatoduodenostomy for choledochal cyst over a period of 9 years were included in this study.Results The patients operated upon had outcomes similar to those treated by the Roux-en-Y technique in other studies.Conclusion Hepaticoduodenostomy is an effective alternative to the conventional Roux-en-Y anastomotic technique in cases of choledochal cyst in children. Keywords: choledochal cyst, hepaticoduodenostomy, pediatri

Preliminary assessment of the irradiation behaviour of the FeCrMnNi High-Entropy Alloy for nuclear applications

In the search for new nuclear materials with improved radiation tolerance and behavior, the high-entropy alloys (HEAs) have arisen as new candidates for structural components in nuclear reactors due to their suspected superior stability under irradiation. The metallurgical definition of HEAs is any alloy with multiple elements, five or more all in equiatomic compositions. The basic principle is the high mixing entropy of its solid solution lowers the Gibbs free energy giving a strong enhancement of the microstructural stability at low and high temperatures. The objective of this project is to assess the irradiation behaviour of the FeCrMnNi HEA system in order to investigate whether the high entropy effect is responsible for a microstructure with better radiation resistance compared to conventional alloys. In this work transmission electron microscopy (TEM) with in-situ ion irradiation has been used at the MIAMI-1 facility at the University of Huddersfield, UK: a 100 kV ion accelerator coupled with a JEOL JEM-2000FX TEM. This methodology allows the evolution of the HEA microstructure to be studied on the nanoscale during the ion irradiation

Preliminary assessment of the irradiation behaviour of the FeCrMnNi High-Entropy Alloy for nuclear applications

In the search for new nuclear materials with improved radiation tolerance and behavior, the high-entropy alloys (HEAs) have arisen as new candidates for structural components in nuclear reactors due to their suspected superior stability under irradiation. The metallurgical definition of HEAs is any alloy with multiple elements, five or more all in equiatomic compositions. The basic principle is the high mixing entropy of its solid solution lowers the Gibbs free energy giving a strong enhancement of the microstructural stability at low and high temperatures. The objective of this project is to assess the irradiation behaviour of the FeCrMnNi HEA system in order to investigate whether the high entropy effect is responsible for a microstructure with better radiation resistance compared to conventional alloys. In this work transmission electron microscopy (TEM) with in-situ ion irradiation has been used at the MIAMI-1 facility at the University of Huddersfield, UK: a 100 kV ion accelerator coupled with a JEOL JEM-2000FX TEM. This methodology allows the evolution of the HEA microstructure to be studied on the nanoscale during the ion irradiation

Fast algorithm for calculating two-photon absorption spectra

We report a numerical calculation of the two-photon absorption coefficient of electrons in a binding potential using the real-time real-space higher-order difference method. By introducing random vector averaging for the intermediate state, the task of evaluating the two-dimensional time integral is reduced to calculating two one-dimensional integrals. This allows the reduction of the computation load down to the same order as that for the linear response function. The relative advantage of the method compared to the straightforward multi-dimensional time integration is greater for the calculation of non-linear response functions of higher order at higher energy resolution.Comment: 4 pages, 2 figures. It will be published in Phys. Rev. E on 1, March, 199