Dynamic Scaling of Non-Euclidean Interfaces

The dynamic scaling of curved interfaces presents features that are strikingly different from those of the planar ones. Spherical surfaces above one dimension are flat because the noise is irrelevant in such cases. Kinetic roughening is thus a one-dimensional phenomenon characterized by a marginal logarithmic amplitude of the fluctuations. Models characterized by a planar dynamical exponent $z>1$, which include the most common stochastic growth equations, suffer a loss of correlation along the interface, and their dynamics reduce to that of the radial random deposition model in the long time limit. The consequences in several applications are discussed, and we conclude that it is necessary to reexamine some experimental results in which standard scaling analysis was applied

Rac1/WAVE2 and Cdc42/N-WASP Participation in Actin-Dependent Host Cell Invasion by Extracellular Amastigotes of Trypanosoma cruzi

This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups. Overexpression of constitutively active constructs of Rac1 and RhoA altered the morphology of actin recruitments to EA invasion sites. Additionally, EA internalization was increased in cells overexpressing CA-Rac1 but inhibited in cells overexpressing CA-RhoA. WT-Cdc42 expression increased EA internalization, but curiously, CA-Cdc42 inhibited it. Altogether, these results corroborate the hypothesis of EA internalization in non-phagocytic cells by a phagocytosis-like mechanism and present Rac1 as the key Rho-family GTPase in this process.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e TecnologicoUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo, BrazilFAPESP: 2012/21335-8, 2011/51475-3CNPq: 302068/2016-3Web of Scienc

Universal fluctuations in radial growth models belonging to the KPZ universality class

We investigate the radius distributions (RD) of surfaces obtained with large-scale simulations of radial clusters that belong to the KPZ universality class. For all investigated models, the RDs are given by the Tracy-Widom distribution of the Gaussian unitary ensemble, in agreement with the conjecture of the KPZ universality class for curved surfaces. The quantitative agreement was also confirmed by two-point correlation functions asymptotically given by the covariance of the Airy$_2$ process. Our simulation results fill the last lacking gap of the conjecture that had been recently verified analytically and experimentally.Comment: 5 pages, 5 figure

Amastigote Synapse: The Tricks of Trypanosoma cruzi Extracellular Amastigotes

To complete its life cycle within the mammalian host, Trypanosoma cruzi, the agent of Chagas’ disease, must enter cells. Trypomastigotes originating from the insect vector (metacyclic) or from infected cells (bloodstream/tissue culture-derived) are the classical infective forms of the parasite and enter mammalian cells in an actin-independent manner. By contrast, amastigotes originating from the premature rupture of infected cells or transformed from swimming trypomastigotes (designated extracellular amastigotes, EAs) require functional intact microfilaments to invade non-phagocytic host cells. Earlier work disclosed the key features of EA-HeLa cell interplay: actin-rich protrusions called ‘cups’ are formed at EA invasion sites on the host cell membrane that are also enriched in actin-binding proteins, integrins and extracellular matrix elements. In the past decades we described the participation of membrane components and secreted factors from EAs as well as the actin-regulating proteins of host cells involved in what we propose to be a phagocytic-like mechanism of parasite uptake. Thus, regarding this new perspective herein we present previously described EA-induced ‘cups’ as parasitic synapse since they can play a role beyond its architecture function. In this review, we focus on recent findings that shed light on the intricate interaction between extracellular amastigotes and non-phagocytic HeLa cells

Relativistic resonances: Their masses, widths, lifetimes, superposition, and causal evolution

Whether one starts form the analytic S-matrix definition or the requirement of gauge parameter independence in renormalization theory, a relativistic resonance is given by a pole at a complex value s of energy squared. The complex number s does not define the mass and width separately and this definition does not lead to interfering Breit-Wigner if two or more resonances are involved. To accomplish both we invoke the decaying particle aspect of a resonance and associate to each pole a space of relativistic Gamow kets which transform irreducibly under causal Poincare transformations. A Gamow state has an exponential time evolution and one can choose of the many possible width parameters, that parameter as the width of the relativistic resonance which equals the inverse lifetime. This uniquely defines the mass and width parameters for a relativistic resonance. Two or more poles in the same partial wave are given by the sum of Breit-Wigners in the scattering amplitude and by a superposition of Gamow vectors with each Gamow vector corresponding to one Breit-Wigner. In addition to the sum of Breit-Wigners the scattering amplitude contains a background amplitude representing direct production of the final state (contact terms).This contact amplitude is associated to a background vector which is a continuous superposition of Lippmann-Schwinger states. Omitting this continuum gives the Weisskopf-Wigner approximation.Comment: 22 pages, REVTe

On the Mass and Width of the Z-boson and Other Relativistic Quasistable Particles

The ambiguity in the definition for the mass and width of relativistic resonances is discussed, in particular for the case of the Z-boson. This ambiguity can be removed by requiring that a resonance's width $\Gamma$ (defined by a Breit-Wigner lineshape) and lifetime $\tau$ (defined by the exponential law) always and exactly fulfill the relation $\Gamma = \hbar/\tau$. To justify this one needs relativistic Gamow vectors which in turn define the resonance's mass M_R as the real part of the square root $\rm{Re}\sqrt{s_R}$ of the S-matrix pole position s_R. For the Z-boson this means that $M_R \approx M_Z - 26{MeV}$ and $\Gamma_R \approx \Gamma_Z-1.2{MeV}$ where M_Z and $\Gamma_Z$ are the values reported in the particle data tables.Comment: 23 page

Parasite-mediated remodeling of the host microfilament cytoskeleton enables rapid egress of Trypanosoma cruzi following membrane rupture

Chagas’ disease arises as a direct consequence of the lytic cycle of Trypanosoma cruzi in the mammalian host. While invasion is well studied for this patho-gen, study of egress has been largely neglected. Here, we provide the first description of T. cruzi egress documenting a coordinated mechanism by which T. cruzi engineers its escape from host cells in which it has proliferated and which is essential for mainte-nance of infection and pathogenesis. Our results indicate that this parasite egress is a sudden event involving coordinated remodeling of host cell cytoskeleton and subsequent rupture of host cell plasma membrane. We document that host cells maintain plasma membrane integrity until immediately prior to parasite release and report the sequential transformation of the host cell’s actin cytoskeleton from normal meshwork in noninfected cells to spheroidal cages—a process initiated shortly after amastigogenesis. Quantification revealed gradual reduction in F-actin over the course of infection, and using cytoskeletal preparations and electron microscopy, we were able to observe disruption of the F-actin proximal to intracellular trypomastigotes. Finally, Western blotting experiments suggest actin degradation driven by parasite proteases, suggesting that degradation of cytoskeleton is a principal component controlling the initiation of egress. Our results provide the first description of the cellular mechanism that regulates the lytic component of the T. cruzi lytic cycle. We show graphically how it is possible to pre-serve the envelope of host cell plasma membrane during intracellular proliferation of the parasite and how, in cells packed with amastigotes, differentiation into trypomasti-gotes may trigger sudden egress

Convergence of miRNA Expression Profiling, α-Synuclein Interacton and GWAS in Parkinson's Disease

miRNAs were recently implicated in the pathogenesis of numerous diseases, including neurological disorders such as Parkinson's disease (PD). miRNAs are abundant in the nervous system, essential for efficient brain function and play important roles in neuronal patterning and cell specification. To further investigate their involvement in the etiology of PD, we conducted miRNA expression profiling in peripheral blood mononuclear cells (PBMCs) of 19 patients and 13 controls using microarrays. We found 18 miRNAs differentially expressed, and pathway analysis of 662 predicted target genes of 11 of these miRNAs revealed an over-representation in pathways previously linked to PD as well as novel pathways. To narrow down the genes for further investigations, we undertook a parallel approach using chromatin immunoprecipitation-sequencing (ChIP-seq) analysis to uncover genome-wide interactions of α-synuclein, a molecule with a central role in both monogenic and idiopathic PD. Convergence of ChIP-seq and miRNomics data highlighted the glycosphingolipid biosynthesis and the ubiquitin proteasome system as key players in PD. We then tested the association of target genes belonging to these pathways with PD risk, and identified nine SNPs in USP37 consistently associated with PD susceptibility in three genome-wide association studies (GWAS) datasets (0.46≤OR≤0.63) and highly significant in the meta-dataset (3.36×10−4<p<1.94×10−3). A SNP in ST8SIA4 was also highly associated with PD (p = 6.15×10−3) in the meta-dataset. These findings suggest that several miRNAs may act as regulators of both known and novel biological processes leading to idiopathic PD

Genetic characterisation of Norovirus strains in outpatient children from rural communities of Vhembe district / South Africa, 2014-2015

Background: Norovirus (NoV) is now the 24 most common causes of both outbreaks and sporadic non-bacterial gastroenteritis worldwide. However, data supporting the role of NoV in diarrheal disease are limited in the African continent. Objectives: This study investigates the distribution of NoV genotypes circulating in outpatient children from rural communities of Vhembe district / South Africa. Study design: Stool specimens were collected from children under five years of age with diarrhea, and controls without diarrhea, between July 2014 and April 2015. NoV positive samples, detected previously by Realtime PCR, were analysed using conventional RT-PCR targeting the partial capsid and polymerase genes. Nucleotide sequencing methods were performed to genotype the strains. Results: The sequence analyses demonstrated multiple NoV genotypes including GI.4 (13.8%), GI.5 (6.9%), GII.14 (6.9%), GII.4 (31%), GII.6 (3.4%), GII.P15 (3.4%), GII.P21 (3.4%) and GII.Pe (31%). The most prevalent NoV genotypes were GII.4 Sydney 2012 variants (n=7) among the capsid genotypes, GII.Pe (n=9) among the polymerase genotypes and GII.Pe/GII.4 Sydney 2012 (n=8) putative recombinants among the RdRp/Capsid genotypes. Two unassigned GII.4 variants were found. Conclusions: The findings highlighted NoV genetic diversity and revealed continuous pandemic spread and predominance of GII.Pe/GII.4 Sydney 2012, indicative of increased NoV activity. An unusual RdRp genotype GII.P15 and two unassigned GII.4 variants were also identified from rural settings of the Vhembe district/South Africa. NoV surveillance is warranted to help to inform investigations into NoV evolution and disease burden, and to support on-going vaccine development programmes

Ecological Invasion, Roughened Fronts, and a Competitor's Extreme Advance: Integrating Stochastic Spatial-Growth Models

Both community ecology and conservation biology seek further understanding of factors governing the advance of an invasive species. We model biological invasion as an individual-based, stochastic process on a two-dimensional landscape. An ecologically superior invader and a resident species compete for space preemptively. Our general model includes the basic contact process and a variant of the Eden model as special cases. We employ the concept of a "roughened" front to quantify effects of discreteness and stochasticity on invasion; we emphasize the probability distribution of the front-runner's relative position. That is, we analyze the location of the most advanced invader as the extreme deviation about the front's mean position. We find that a class of models with different assumptions about neighborhood interactions exhibit universal characteristics. That is, key features of the invasion dynamics span a class of models, independently of locally detailed demographic rules. Our results integrate theories of invasive spatial growth and generate novel hypotheses linking habitat or landscape size (length of the invading front) to invasion velocity, and to the relative position of the most advanced invader.Comment: The original publication is available at www.springerlink.com/content/8528v8563r7u2742