The Evolution of Travelling Waves in a KPP Reaction-Diffusion Model with Cut-off Reaction Rate. I. Permanent Form Travelling Waves

We consider Kolmogorov--Petrovskii--Piscounov (KPP) type models in the presence of a discontinuous cut-off in reaction rate at concentration $u=u_c$. In Part I we examine permanent form travelling wave solutions (a companion paper, Part II, is devoted to their evolution in the large time limit). For each fixed cut-off value $0<u_c<1$, we prove the existence of a unique permanent form travelling wave with a continuous and monotone decreasing propagation speed $v^*(u_c)$. We extend previous asymptotic results in the limit of small $u_c$ and present new asymptotic results in the limit of large $u_c$ which are respectively obtained via the systematic use of matched and regular asymptotic expansions. The asymptotic results are confirmed against numerical results obtained for the particular case of a cut-off Fisher reaction function

Switching on the Lights for Gene Therapy

Strategies for non-invasive and quantitative imaging of gene expression in vivo have been developed over the past decade. Non-invasive assessment of the dynamics of gene regulation is of interest for the detection of endogenous disease-specific biological alterations (e.g., signal transduction) and for monitoring the induction and regulation of therapeutic genes (e.g., gene therapy). To demonstrate that non-invasive imaging of regulated expression of any type of gene after in vivo transduction by versatile vectors is feasible, we generated regulatable herpes simplex virus type 1 (HSV-1) amplicon vectors carrying hormone (mifepristone) or antibiotic (tetracycline) regulated promoters driving the proportional co-expression of two marker genes. Regulated gene expression was monitored by fluorescence microscopy in culture and by positron emission tomography (PET) or bioluminescence (BLI) in vivo. The induction levels evaluated in glioma models varied depending on the dose of inductor. With fluorescence microscopy and BLI being the tools for assessing gene expression in culture and animal models, and with PET being the technology for possible application in humans, the generated vectors may serve to non-invasively monitor the dynamics of any gene of interest which is proportionally co-expressed with the respective imaging marker gene in research applications aiming towards translation into clinical application

Carbon Nanotubes Enhance Cytotoxicity Mediated by Human Lymphocytes In Vitro

With the expansion of the potential applications of carbon nanotubes (CNT) in biomedical fields, the toxicity and biocompatibility of CNT have become issues of growing concern. Since the immune system often mediates tissue damage during pathogenesis, it is important to explore whether CNT can trigger cytotoxicity through affecting the immune functions. In the current study, we evaluated the influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The results showed that while CNT at low concentrations (0.001 to 0.1 µg/ml) did not cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated cytotoxicity against multiple human cell lines. In addition, CNT increased the secretion of IFN-γ and TNF-α by the lymphocytes. CNT also upregulated the NF-κB expression in lymphocytes, and the blockage of the NF-κB pathway reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results suggest that CNT at lower concentrations may prospectively initiate an indirect cytotoxicity through affecting the function of lymphocytes

Friction forces position the neural anlage

During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage. Using a combination of experiments and simulations, we show that this process depends on hydrodynamic coupling between neurectoderm and ppl as a result of E-cadherin-mediated adhesion between those tissues. Our data thus establish the emergence of friction forces at the interface between moving tissues as a critical force-generating process shaping the embryo

Use of Hepatitis C-Positive Donor Livers in Liver Transplantation

PURPOSE OF REVIEW: The purpose of this article is to review recent literature regarding the use of Hepatitis C virus (HCV) positive donor livers in liver transplantation. Given the prevalence of HCV-positive patients on the waitlist coupled with high waitlist mortality, use of HCV-positive livers may be a means to meet patient needs. This review seeks to primarily answer the following questions: can HCV-positive livers be used safely and effectively? Are new direct acting antiviral medications safe and effective in HCV-positive liver recipients? RECENT FINDINGS: Use of HCV-positive donor livers for liver transplantation in HCV-positive recipients is increasing. These donor livers have equivalent patient and graft survival when compared to HCV-negative donor livers in HCV-positive liver transplant recipients. Recent studies suggest that use of direct acting antiviral medications in HCV-positive liver transplant recipients can be successful, although there is insufficient data for their use in recipients of HCV-positive donor livers. SUMMARY: HCV-positive donor livers may be safely and effectively used in HCV-positive liver transplant recipients. Direct acting antiviral medications appear safe and effective in HCV-positive liver transplant recipients, but data on their efficacy in HCV-positive liver transplant recipients are limited. Future research should focus on the use of HCV-positive donor livers in HCV-negative liver transplant recipients

Inhibitory signalling to the Arp2/3 complex steers cell migration

International audienceCell migration requires the generation of branched actin networks that power the protrusion of the plasma membrane in lamellipodia. The actin-related proteins 2 and 3 (Arp2/3) complex is the molecular machine that nucleates these branched actin networks. This machine is activated at the leading edge of migrating cells by Wiskott-Aldrich syndrome protein (WASP)-family verprolin-homologous protein (WAVE, also known as SCAR). The WAVE complex is itself directly activated by the small GTPase Rac, which induces lamellipodia. However, how cells regulate the directionality of migration is poorly understood. Here we identify a new protein, Arpin, that inhibits the Arp2/3 complex in vitro, and show that Rac signalling recruits and activates Arpin at the lamellipodial tip, like WAVE. Consistently, after depletion of the inhibitory Arpin, lamellipodia protrude faster and cells migrate faster. A major role of this inhibitory circuit, however, is to control directional persistence of migration. Indeed, Arpin depletion in both mammalian cells and Dictyostelium discoideum amoeba resulted in straighter trajectories, whereas Arpin microinjection in fish keratocytes, one of the most persistent systems of cell migration, induced these cells to turn. The coexistence of the Rac-Arpin-Arp2/3 inhibitory circuit with the Rac-WAVE-Arp2/3 activatory circuit can account for this conserved role of Arpin in steering cell migration