Vacuolar ATPase depletion contributes to dysregulation of endocytosis in bloodstream forms of Trypanosoma brucei

BACKGROUND Vacuolar H-ATPase (V-ATPase) is a highly conserved protein complex which hydrolyzes ATP and pumps protons to acidify vacuolar vesicles. Beyond its role in pH maintenance, the involvement of V-ATPase in endocytosis is well documented in mammals and plants but is less clear in Trypanosoma brucei. METHODS In this study, the subcellular localization of V-ATPase subunit B (TbVAB) of T. brucei was assessed via in situ N-terminal YFP-tagging and immunofluorescence assays. Transgenic bloodstream forms (BSF) of T. brucei were generated which comprised either a V-ATPase subunit B (TbVAB) conditional knockout or a V-ATPase subunit A (TbVAA) knockdown. Acridine orange and BCECF-AM were employed to assess the roles of V-ATPase in the pH regulation of BSF T. brucei. The endocytic activities of three markers were also characterized by flow cytometry analyses. Furthermore, trypanosomes were counted from trypanolysis treatment groups (either containing 1% or 5% NHS) and endocytosed trypanosome lytic factor (TLF) was also analyzed by an immunoblotting assay. RESULTS TbVAB was found to localize to acidocalcisomes, lysosomes and probably also to endosomes of BSF of T. brucei and was demonstrated to be essential for cell growth. TbVAB depletion neutralized acidic organelles at 24 hours post-tetracycline depletion (hpd), meanwhile the steady state intracellular pH increased from 7.016 ± 0.013 to 7.422 ± 0.058. Trypanosomes with TbVAB depletion at 24 hpd were found to take up more transferrin (2.068 ± 0.277 fold) but less tomato lectin (49.31 ± 22.57%) by endocytosis, while no significant change was detected in dextran uptake. Similar endocytic dysregulated phenotypes were also observed in TbVAA knockdown cells. In addition, TbVAB depleted trypanosomes showed a low uptake of TLF and exhibited less sensitive to lysis in both 1% and 5% NHS treatments. CONCLUSIONS TbVAB is a key component of V-ATPase and was found to play a key function in endocytosis as well as exhibiting different effects in a receptor/cargo dependent manner in BSF of T. brucei. Besides vacuolar alkalinization, the dysregulation of endocytosis in TbVAB depleted T. brucei is considered to contribute to the reduced sensitivity to lysis by normal human serum

Dissipative chaotic scattering

We show that weak dissipation, typical in realistic situations, can have a metamorphic consequence on nonhyperbolic chaotic scattering in the sense that the physically important particle-decay law is altered, no matter how small the amount of dissipation. As a result, the previous conclusion about the unity of the fractal dimension of the set of singularities in scattering functions, a major claim about nonhyperbolic chaotic scattering, may not be observable.Comment: 4 pages, 2 figures, revte

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

Disentangling the jet emission from protostellar systems. The ALMA view of VLA1623

Context: High-resolution studies of class 0 protostars represent the key to constraining protostar formation models. VLA16234-2417 represents the prototype of class 0 protostars, and it has been recently identified as a triple non-coeval system. Aim: We aim at deriving the physical properties of the jets in VLA16234-2417 using tracers of shocked gas. Methods: ALMA Cycle 0 Early Science observations of CO(2-1) in the extended configuration are presented in comparison with previous SMA CO(3-2) and Herschel-PACS [OI}] 63 micron observations. Gas morphology and kinematics were analysed to constrain the physical structure and origin of the protostellar outflows. Results: We reveal a collimated jet component associated with the [OI] 63 micron emission at about 8'' (about 960 AU) from source B. This newly detected jet component is inversely oriented with respect to the large-scale outflow driven by source A, and it is aligned with compact and fast jet emission very close to source B (about 0.3'') rather than with the direction perpendicular to the A disk. We also detect a cavity-like structure at low projected velocities, which surrounds the [OI] 63 micron emission and is possibly associated with the outflow driven by source A. Finally, no compact outflow emission is associated with source W. Conclusions: Our high-resolution ALMA observations seem to suggest there is a fast and collimated jet component associated with source B. This scenario would confirm that source B is younger than A, that it is in a very early stage of evolution, and that it drives a faster, more collimated, and more compact jet with respect to the large-scale slower outflow driven by A. However, a different scenario of a precessing jet driven by A cannot be firmly excluded from the present observations.Comment: Accepted for publication in Astronomy & Astrophysic

Surface response of spherical core-shell structured nanoparticle by optically induced elastic oscillations of soft shell against hard core

The optically induced oscillatory response of a spherical two-component, shell-core structured, nanoparticle by nodeless elastic vibrations of soft peripheral shell against hard and dynamically immobile inner core is considered. The eigenfrequencies of the even-parity, spheroidal and odd-parity torsional vibrational modes trapped in the finite-depth shell are obtained which are of practical interest for modal specification of individual resonances in spectra of resonant scattering of long wavelength electromagnetic waves by ultrafine particles.Comment: Surface Review and Letters (World Scientific) Year: 2009 Vol: 16 Issue: 1 (February 2009) Page: 5 - 1

Innermost Stable Circular Orbit of Inspiraling Neutron-Star Binaries: Tidal Effects, Post-Newtonian Effects and the Neutron-Star Equation of State

We study how the neutron-star equation of state affects the onset of the dynamical instability in the equations of motion for inspiraling neutron-star binaries near coalescence. A combination of relativistic effects and Newtonian tidal effects cause the stars to begin their final, rapid, and dynamically-unstable plunge to merger when the stars are still well separated and the orbital frequency is $\approx$ 500 cycles/sec (i.e. the gravitational wave frequency is approximately 1000 Hz). The orbital frequency at which the dynamical instability occurs (i.e. the orbital frequency at the innermost stable circular orbit) shows modest sensitivity to the neutron-star equation of state (particularly the mass-radius ratio, $M/R_o$, of the stars). This suggests that information about the equation of state of nuclear matter is encoded in the gravitational waves emitted just prior to the merger.Comment: RevTeX, to appear in PRD, 8 pages, 4 figures include

On the Possible Enhancement of the Magnetic Field by Neutrino Reemission Processes in the Mantle of a Supernova

URCA neutrino reemission processes under the conditions in the mantle of a supernova with a strong toroidal magnetic field are investigated. It is shown that parity violation in these processes can be manifested macroscopically as a torque that rapidly spins up the region of the mantle occupied by such a field. Neutrino spin-up of the mantle can strongly affect the mechanism of further generation of the toroidal field, specifically, it can enhance the field in a small neighborhood of the rigid-body-rotating core of the supernova remnant.Comment: 8 pages, late

Nonlinear Waves in Disordered Diatomic Granular Chains

We investigate the propagation and scattering of highly nonlinear waves in disordered granular chains composed of diatomic (two-mass) units of spheres that interact via Hertzian contact. Using ideas from statistical mechanics, we consider each diatomic unit to be a "spin", so that a granular chain can be viewed as a spin chain composed of units that are each oriented in one of two possible ways. Experiments and numerical simulations both reveal the existence of two different mechanisms of wave propagation: In low-disorder chains, we observe the propagation of a solitary pulse with exponentially decaying amplitude. Beyond a critical level of disorder, the wave amplitude instead decays as a power law, and the wave transmission becomes insensitive to the level of disorder. We characterize the spatio-temporal structure of the wave in both propagation regimes and propose a simple theoretical interpretation for such a transition. Our investigation suggests that an elastic spin chain can be used as a model system to investigate the role of heterogeneities in the propagation of highly nonlinear waves.Comment: 10 pages, 8 figures (some with multiple parts), to appear in Physical Review E; summary of changes: new title, one new figure, additional discussion of several points (including both background and results

New method to study stochastic growth equations: a cellular automata perspective

We introduce a new method based on cellular automata dynamics to study stochastic growth equations. The method defines an interface growth process which depends on height differences between neighbors. The growth rule assigns a probability $p_{i}(t)=\rho$ exp$[\kappa \Gamma_{i}(t)]$ for a site $i$ to receive one particle at a time $t$ and all the sites are updated simultaneously. Here $\rho$ and $\kappa$ are two parameters and $\Gamma_{i}(t)$ is a function which depends on height of the site $i$ and its neighbors. Its functional form is specified through discretization of the deterministic part of the growth equation associated to a given deposition process. In particular, we apply this method to study two linear equations - the Edwards-Wilkinson (EW) equation and the Mullins-Herring (MH) equation - and a non-linear one - the Kardar-Parisi-Zhang (KPZ) equation. Through simulations and statistical analysis of the height distributions of the profiles, we recover the values for roughening exponents, which confirm that the processes generated by the method are indeed in the universality classes of the original growth equations. In addition, a crossover from Random Deposition to the associated correlated regime is observed when the parameter $\kappa$ is varied.Comment: 6 pages, 7 figure