Modeling effects of L-type ca(2+) current and na(+)-ca(2+) exchanger on ca(2+) trigger flux in rabbit myocytes with realistic T-tubule geometries.

The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+) current affects intracellular Ca(2+) dynamics. Our model includes a realistic 3D geometry of a single t-tubule and its surrounding half-sarcomeres for rabbit ventricular myocytes. The effects of spatially distributed membrane ion-transporters (LCC, Na(+)/Ca(2+) exchanger, sarcolemmal Ca(2+) pump, and sarcolemmal Ca(2+) leak), and stationary and mobile Ca(2+) buffers (troponin C, ATP, calmodulin, and Fluo-3) are also considered. We used a coupled reaction-diffusion system to describe the spatio-temporal concentration profiles of free and buffered intracellular Ca(2+). We obtained parameters from voltage-clamp protocols of L-type Ca(2+) current and line-scan recordings of Ca(2+) concentration profiles in rabbit cells, in which the sarcoplasmic reticulum is disabled. Our model results agree with experimental measurements of global Ca(2+) transient in myocytes loaded with 50 μM Fluo-3. We found that local Ca(2+) concentrations within the cytosol and sub-sarcolemma, as well as the local trigger fluxes of Ca(2+) crossing the cell membrane, are sensitive to details of t-tubule micro-structure and membrane Ca(2+) flux distribution. The model additionally predicts that local Ca(2+) trigger fluxes are at least threefold to eightfold higher than the whole-cell Ca(2+) trigger flux. We found also that the activation of allosteric Ca(2+)-binding sites on the Na(+)/Ca(2+) exchanger could provide a mechanism for regulating global and local Ca(2+) trigger fluxes in vivo. Our studies indicate that improved structural and functional models could improve our understanding of the contributions of L-type and Na(+)/Ca(2+) exchanger fluxes to intracellular Ca(2+) dynamics

Dynamics of Nanometer-Scale Foil Targets Irradiated with Relativistically Intense Laser Pulses

In this letter we report on an experimental study of high harmonic radiation generated in nanometer-scale foil targets irradiated under normal incidence. The experiments constitute the first unambiguous observation of odd-numbered relativistic harmonics generated by the $\vec{v}\times\vec{B}$ component of the Lorentz force verifying a long predicted property of solid target harmonics. Simultaneously the observed harmonic spectra allow in-situ extraction of the target density in an experimental scenario which is of utmost interest for applications such as ion acceleration by the radiation pressure of an ultraintense laser.Comment: 5 pages, 4 figure

Molecular and Subcellular-Scale Modeling of Nucleotide Diffusion in the Cardiac Myofilament Lattice

AbstractContractile function of cardiac cells is driven by the sliding displacement of myofilaments powered by the cycling myosin crossbridges. Critical to this process is the availability of ATP, which myosin hydrolyzes during the cross-bridge cycle. The diffusion of adenine nucleotides through the myofilament lattice has been shown to be anisotropic, with slower radial diffusion perpendicular to the filament axis relative to parallel, and is attributed to the periodic hexagonal arrangement of the thin (actin) and thick (myosin) filaments. We investigated whether atomistic-resolution details of myofilament proteins can refine coarse-grain estimates of diffusional anisotropy for adenine nucleotides in the cardiac myofibril, using homogenization theory and atomistic thin filament models from the Protein Data Bank. Our results demonstrate considerable anisotropy in ATP and ADP diffusion constants that is consistent with experimental measurements and dependent on lattice spacing and myofilament overlap. A reaction-diffusion model of the half-sarcomere further suggests that diffusional anisotropy may lead to modest adenine nucleotide gradients in the myoplasm under physiological conditions

Structural and functional alterations in salivary gland chromosomes and enzyme activity of Chironomus riparius Mg. (Diptera, Chironomidae) from anthropogenically polluted sites in Bulgaria and Turkey

The effect of environment contaminants on genome instability and changes in enzyme activity (acetylcholinesterase (AChE), glutathione S-transferase activities (GST), etoxyresorufin O-deethylase (EROD) and metallothionein (MT)) of Chironomus riparius Mg. from Bulgarian and Turkish stations over two years (2009, 2010) as well as laboratory reared larvae were studied. Physicochemical analysis of the sediments from the field stations indicated the presence of heavy metal pollutants (Cr, Cu, Mn, Pb, and Cd) whose concentrations were higher than the reference data. Genome instability was determined by somatic structural and functional alterations of the polytene chromosomes. In the field sites of both countries somatic aberrations occurred at a significantly higher frequency (p < 0.001) compared with control and laboratory material. C. riparius in sediments with higher concentrations of trace metals (Derincay River, Turkey and Chaya River, Bulgaria), was found to possess a high spectrum of somatic chromosome rearrangements with a somatic index of 2.53 and 3.25 respectively. Changes in functional activity included decreased activity of the Balbiani rings (BRs) and nucleolar organizer (NOR). The observed chromosome alterations agree with the high degree of trace metal pollution and high activity of the studied enzymes. However, no correlation between single somatic chromosome rearrangements and concentrations of specific metal ions was defined. The data are discussed in the light of the wide variety of interactions of metals in nature. The results show that the genome response and biochemical markers are sensitive markers of toxicity and provide early warning indicators of contaminants in the environment. © 2012 Dipartimento di Biologia Evoluzionistica

Building professional discourse in emerging markets: Language, context and the challenge of sensemaking

Using ethnographic evidence from the former Soviet republics, this article examines a relatively new and mainly unobserved in the International Business (IB) literature phenomenon of communication disengagement that manifests itself in many emerging markets. We link it to the deficiencies of the local professional business discourse rooted in language limitations reflecting lack of experience with the market economy. This hampers cognitive coherence between foreign and local business entities, adding to the liability of foreignness as certain instances of professional experience fail to find adequate linguistic expression, and complicates cross-cultural adjustments causing multi-national companies (MNCs) financial losses. We contribute to the IB literature by examining cross-border semantic sensemaking through a retrospectively constructed observational study. We argue that a relative inadequacy of the national professional idiom is likely to remain a feature of business environment in post-communist economies for some time and therefore should be factored into business strategies of MNCs. Consequently, we recommend including discursive hazards in the risk evaluation of international projects

Numerical Analysis of Ca2+ Signaling in Rat Ventricular Myocytes with Realistic Transverse-Axial Tubular Geometry and Inhibited Sarcoplasmic Reticulum

The t-tubules of mammalian ventricular myocytes are invaginations of the cell membrane that occur at each Z-line. These invaginations branch within the cell to form a complex network that allows rapid propagation of the electrical signal, and hence synchronous rise of intracellular calcium (Ca2+). To investigate how the t-tubule microanatomy and the distribution of membrane Ca2+ flux affect cardiac excitation-contraction coupling we developed a 3-D continuum model of Ca2+ signaling, buffering and diffusion in rat ventricular myocytes. The transverse-axial t-tubule geometry was derived from light microscopy structural data. To solve the nonlinear reaction-diffusion system we extended SMOL software tool (http://mccammon.ucsd.edu/smol/). The analysis suggests that the quantitative understanding of the Ca2+ signaling requires more accurate knowledge of the t-tubule ultra-structure and Ca2+ flux distribution along the sarcolemma. The results reveal the important role for mobile and stationary Ca2+ buffers, including the Ca2+ indicator dye. In agreement with experiment, in the presence of fluorescence dye and inhibited sarcoplasmic reticulum, the lack of detectible differences in the depolarization-evoked Ca2+ transients was found when the Ca2+ flux was heterogeneously distributed along the sarcolemma. In the absence of fluorescence dye, strongly non-uniform Ca2+ signals are predicted. Even at modest elevation of Ca2+, reached during Ca2+ influx, large and steep Ca2+ gradients are found in the narrow sub-sarcolemmal space. The model predicts that the branched t-tubule structure and changes in the normal Ca2+ flux density along the cell membrane support initiation and propagation of Ca2+ waves in rat myocytes

Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

<p>Abstract</p> <p>Background</p> <p>Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment for patients with peritoneal carcinomatosis (PC). Our objective was to identify new prognostic factors in patients with PC from colorectal cancer treated with this procedure.</p> <p>Methods</p> <p>All patients with PC from colorectal cancer treated by HIPEC from January 2000 to December 2007 were prospectively included. The tumor extension was assessed by the Peritoneal Cancer Index (PCI) and the residual disease was recorded using the completeness cytoreductive score (CCs). All clinical and treatment data were computed in univariate and multivariable analyses using survival as primary end point.</p> <p>Results</p> <p>We carried out 51 complete procedures in 49 consecutive patients. The mean PCI was 10. The allocation of CCs was: CC-0 = 37, CC-1 = 14. The five-year overall and progression-free survival rate were 40% and 20%, respectively. Several prognostic factors for survival were identified by univariate analysis: PCI < 9 (<it>P </it>< 0.001), CC-0 vs. CC-1 (<it>P </it>< 0.01) and involvement of area 4 (<it>P </it>= 0.06), area 5 (<it>P </it>= 0.031), area 7 (<it>P </it>= 0.014), area 8 (<it>P </it>= 0.022), area 10 (<it>P </it>< 0.0001), and area 11 (<it>P </it>= 0.02). Only the involvement of the distal jejunum (area 10) was significant in the multivariable analysis (<it>P </it>= 0.027).</p> <p>Conclusions</p> <p>We demonstrated that the involvement of area 10 (distal jejunum of the PCI score) was an independent factor associated with poor prognosis.</p

Developing international business relationships in a Russian context

The collapse of the former Soviet Union has opened up a wealth of business opportunities for companies seeking new markets in the Russian Federation. Despite this, firms intending to do business in Russia have found themselves hampered by cultural differences in business practices and expectations. As Russia integrates into the global economy, understanding such practices and the managerial mindset of business people is crucial for managers who hope to navigate Russia's complex markets. This study draws on the trust literature and adopts quantitative tools to deconstruct the Russian 'Sviazi' system of social capital business networking. We develop a model isolating three dimensions of Sviazi: one an affective or emotional component; the second, a conative component; and the third, a cognitive component. The model provides a useful guide for helping foreign firms to succeed in Russia, while also serving as a basis for further research in the field. Keywords