A cis-Regulatory Mutation in Troponin-I of Drosophila Reveals the Importance of Proper Stoichiometry of Structural Proteins During Muscle Assembly

Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.

Role of Areca Nut Induced TGF-beta and Epithelial-Mesenchymal Interaction in the Pathogenesis of Oral Submucous Fibrosis

Areca nut consumption has been implicated in the progression of Oral Submucous fibrosis (OSF); an inflammatory precancerous fibrotic condition. Our previous studies have demonstrated the activation of TGF-beta signaling in epithelial cells by areca nut components and also propose a role for epithelial expressed TGF-beta in the pathogenesis of OSF. Although the importance of epithelial cells in the manifestation of OSF has been proposed, the actual effectors are fibroblast cells. However, the role of areca nut and TGF-beta in the context of fibroblast response has not been elucidated. Therefore, to understand their role in the context of fibroblast response in OSF pathogenesis, human gingival fibroblasts (hGF) were treated with areca nut and/or TGF-beta followed by transcriptome profiling. The gene expression profile obtained was compared with the previously published transcriptome profiles of OSF tissues and areca nut treated epithelial cells. The analysis revealed regulation of 4666 and 1214 genes by areca nut and TGF-beta treatment respectively. The expression of 413 genes in hGF cells was potentiated by areca nut and TGF-beta together. Further, the differentially expressed genes of OSF tissues compared to normal tissues overlapped significantly with areca nut and TGF-beta induced genes in epithelial and hGF cells. Several positively enriched pathways were found to be common between OSF tissues and areca nut + TGF-beta treated hGF cells. In concordance, areca nut along with TGF-beta enhanced fibroblast activation as demonstrated by potentiation of alpha SMA, gamma SMA and collagen gel contraction by hGF cells. Furthermore, TGF-beta secreted by areca nut treated epithelial cells influenced fibroblast activation and other genes implicated in fibrosis. These data establish a role for areca nut influenced epithelial cells in OSF progression by activation of fibroblasts and emphasizes the importance of epithelial-mesenchymal interaction in OSF.

Computational modeling of reactive hot pressing of zirconium carbide

A model of reactive hot pressing of zirconium carbide (ZrCx, 0.5 < x < 1) has been constructed that incorporates four processes that occur in parallel: creep of zirconium (Zr), reaction of Zr and carbon (C), increase in volume fraction of hard phase with progressive reaction that reduces the creep of Zr and, finally, de-densification associated with volume reduction during reaction. The reasonable agreement of the model with experimental results verifies that plastic deformation of Zr is the main factor that is responsible for the low-temperature reactive densification of ZrC and that ZrC may be treated as a rigid inclusion that contributes little to densification. It predicts that densification is impaired by increasing carbon stoichiometry due to the increasing amount of starting hard phase and the greater contraction upon reaction. Additionally, the model predicts that mixtures of Zr and ZrC should show equal or better densification than Zr and C mixtures.

DOES THE CHEMOTHERMAL INSTABILITY HAVE ANY ROLE IN THE FRAGMENTATION OF PRIMORDIAL GAS

The collapse of the primordial gas in the density regime similar to 10(8)-10(10) cm(-3) is controlled by the three-body H-2 formation process, in which the gas can cool faster than free-fall time-a condition proposed as the chemothermal instability. We investigate how the heating and cooling rates are affected during the rapid transformation of atomic to molecular hydrogen. With a detailed study of the heating and cooling balance in a 3D simulation of Pop III collapse, we follow the chemical and thermal evolution of the primordial gas in two dark matter minihalos. The inclusion of sink particles in modified Gadget-2 smoothed particle hydrodynamics code allows us to investigate the long-term evolution of the disk that fragments into several clumps. We find that the sum of all the cooling rates is less than the total heating rate after including the contribution from the compressional heating (pdV). The increasing cooling rate during the rapid increase of the molecular fraction is offset by the unavoidable heating due to gas contraction. We conclude that fragmentation occurs because H-2 cooling, the heating due to H-2 formation and compressional heating together set a density and temperature structure in the disk that favors fragmentation, not the chemothermal instability.

A note on tetrablock contractions

A commuting triple of operators (A, B, P) on a Hilbert space H is called a tetrablock contraction if the closure of the set E = {(a(11),a(22),detA) : A = GRAPHICS] with parallel to A parallel to <1} is a spectral set. In this paper, we construct a functional model and produce a set of complete unitary invariants for a pure tetrablock contraction. In this construction, the fundamental operators, which are the unique solutions of the operator equations A - B* P = DPX1DP and B - A* P = DPX2DP where X-1, X-2 is an element of B(D-P) play a pivotal role. As a result of the functional model, we show that every pure tetrablock isometry (A, B, P) on an abstract Hilbert space H is unitarily equivalent to the tetrablock contraction (MG1*+G2z, MG2*+G1z, M-z) on H-DP*(2). (D), where G(1) and G(2) are the fundamental operators of (A*, B*, P*). We prove a Beurling Lax Halmos type theorem for a triple of operators (MF1*+F2z, MF2*+F1z, M-z), where epsilon is a Hilbert space and F-1, F-2 is an element of B(epsilon). We also deal with a natural example of tetrablock contraction on a functions space to find out its fundamental operators.

Design and Validation of On-chip Planar Mixer Based on Advection and Viscoelastic Effects

Mixing at low Reynolds number is usually due to diffusion and requires longer channel lengths for complete mixing. In order to reduce the mixing lengths, advective flow can be induced by varying the channel geometry. Additionally, in non-newtonian fluids, appropriate modifications to channel geometry can be used to aid the mixing process by capitalizing on their viscoelastic nature. Here we have exploited the advection and viscoelastic effects to implement a planar passive micro-mixer. Microfluidic devices incorporating different blend of mixing geometries were conceived. The optimum design was chosen based on the results of the numerical simulations performed in COMSOL. The chosen design had sudden expansion and contraction along with teeth patterns along the channel walls to improve mixing. Mixing of two different dyes was performed to validate the mixing efficiency. Particle dispersion experiments were also carried out. The results indicated effective mixing. In addition, the same design was also found to be compatible with electrical power free pumping mechanism like suction. The proposed design was then used to carry out on-chip chemical cell lysis with human whole blood samples to establish its use with non-newtonian fluids. Complete lysis of the erythrocytes was observed leaving behind the white blood cells at the outlet.