Calcium dependence of exo- and endocytotic coupling at a glutamatergic synapse.

SummaryThe mechanism coupling exocytosis and endocytosis remains to be elucidated at central synapses. Here, we show that the mechanism linking these two processes is dependent on microdomain-[Ca2+]i similar to that which triggers exocytosis, as well as the exocytotic protein synaptobrevin/VAMP. Furthermore, block of endocytosis has a limited, retrograde action on exocytosis, delaying recruitment of release-ready vesicles and enhancing short-term depression. This effect sets in so rapidly that it cannot be explained by the nonavailability of recycled vesicles. Rather, we postulate that perturbation of a step linking exocytosis and endocytosis temporarily prevents new vesicles from docking at specialized sites for exocytosis

Relapsed and/or Refractory Mantle Cell Lymphoma: What Role for Temsirolimus?

Mantle Cell Lymphoma (MCL) is associated with a dismal prognosis. Recently, along with the improved understanding of the pathophysiology of this disease, new first line regimens have been established and in addition novel treatment options have entered the clinical arena. In consequence, prognosis of the disease has fortunately improved. We here focus on the rationale, current clinical knowledge and future concepts of Temsirolimus, an inhibitor of mTOR, in the treatment of MCL. At this time this drug has been shown to be effective as single agent for relapsed disease and early combination data show promising results. In addition, with a brief outline of other treatment options, we aim to guide at which place in the current treatment algorithms Temsirolimus can be integrated into the treatment of MCL patients

Non-Fermi liquid transport in the vicinity of nematic quantum critical point of FeSe1−x_{1-x}Sx_x superconductor

Non-Fermi liquids are strange metals whose physical properties deviate qualitatively from those of conventional metals due to strong quantum fluctuations. In this paper, we report transport measurements on the FeSe$_{1-x}$S$_x$ superconductor, which has a quantum critical point of a nematic order without accompanying antiferromagnetism. We find that in addition to a linear-in-temperature resistivity $\rho_{xx}\propto T$, which is close to the Planckian limit, the Hall angle varies as $\cot \theta_{\rm H} \propto T^2$ and the low-field magnetoresistance is well scaled as $\Delta\rho_{xx}/\rho_{xx}\propto \tan^2 \theta_{\rm H}$ in the vicinity of the nematic quantum critical point. This set of anomalous charge transport properties shows striking resemblance with those reported in cuprate, iron-pnictide and heavy fermion superconductors, demonstrating that the critical fluctuations of a nematic order with ${\bf q} \approx 0$ can also lead to a breakdown of the Fermi liquid description.Comment: 8 pages, 4 + 1 figure

Tuning gastropod locomotion: Modeling the influence of mucus rheology on the cost of crawling

Common gastropods such as snails crawl on a solid substrate by propagating muscular waves of shear stress on a viscoelastic mucus. Producing the mucus accounts for the largest component in the gastropod's energy budget, more than twenty times the amount of mechanical work used in crawling. Using a simple mechanical model, we show that the shear-thinning properties of the mucus favor a decrease in the amount of mucus necessary for crawling, thereby decreasing the overall energetic cost of locomotion.Comment: Corrected typo

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Solving Nonlinear Parabolic Equations by a Strongly Implicit Finite-Difference Scheme

We discuss the numerical solution of nonlinear parabolic partial differential equations, exhibiting finite speed of propagation, via a strongly implicit finite-difference scheme with formal truncation error $\mathcal{O}\left[(\Delta x)^2 + (\Delta t)^2 \right]$. Our application of interest is the spreading of viscous gravity currents in the study of which these type of differential equations arise. Viscous gravity currents are low Reynolds number (viscous forces dominate inertial forces) flow phenomena in which a dense, viscous fluid displaces a lighter (usually immiscible) fluid. The fluids may be confined by the sidewalls of a channel or propagate in an unconfined two-dimensional (or axisymmetric three-dimensional) geometry. Under the lubrication approximation, the mathematical description of the spreading of these fluids reduces to solving the so-called thin-film equation for the current's shape $h(x,t)$. To solve such nonlinear parabolic equations we propose a finite-difference scheme based on the Crank--Nicolson idea. We implement the scheme for problems involving a single spatial coordinate (i.e., two-dimensional, axisymmetric or spherically-symmetric three-dimensional currents) on an equispaced but staggered grid. We benchmark the scheme against analytical solutions and highlight its strong numerical stability by specifically considering the spreading of non-Newtonian power-law fluids in a variable-width confined channel-like geometry (a "Hele-Shaw cell") subject to a given mass conservation/balance constraint. We show that this constraint can be implemented by re-expressing it as nonlinear flux boundary conditions on the domain's endpoints. Then, we show numerically that the scheme achieves its full second-order accuracy in space and time. We also highlight through numerical simulations how the proposed scheme accurately respects the mass conservation/balance constraint.Comment: 36 pages, 9 figures, Springer book class; v2 includes improvements and corrections; to appear as a contribution in "Applied Wave Mathematics II

Do gender and torus mandibularis affect mandibular cortical index? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The interactions between torus and several factors such as age, gender, and dental status have not been studied comprehensively. The purpose of this study was to determine the effect of gender on the mandibular cortical index (MCI) and to investigate a possible association between torus mandibularis (TM) and MCI.</p> <p>Methods</p> <p>The study consisted of 189 consecutive patients referred to Department of Oral Diagnosis and Radiology of Hacettepe University within 30 workdays. Patients who did not have systemic disorders affecting bone density were included; and the age, gender, dental status and existing TM of the patients were recorded. Morphology of the mandibular inferior cortex was determined according to Klemitti's classification on panoramic radiographs.</p> <p>Results</p> <p>MCI was affected by age and gender (<it>P </it>< 0.05). No significant relationship was found between TM and MCI (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>In the study population, MCI was affected by age and gender. As age increased, semilunar defects could be seen on the cortex of the mandible and MCI values increased. Women appeared to have higher MCI values than men.</p