N-cadherin acts in concert with Slit1-Robo2 signaling in regulating aggregation of placode-derived cranial sensory neurons

Vertebrate cranial sensory ganglia have a dual origin from the neural crest and ectodermal placodes. In the largest of these, the trigeminal ganglion, Slit1-Robo2 signaling is essential for proper ganglion assembly. Here, we demonstrate a crucial role for the cell adhesion molecule N-cadherin and its interaction with Slit1-Robo2 during gangliogenesis in vivo. A common feature of chick trigeminal and epibranchial ganglia is the expression of N-cadherin and Robo2 on placodal neurons and Slit1 on neural crest cells. Interestingly, N-cadherin localizes to intercellular adherens junctions between placodal neurons during ganglion assembly. Depletion of N-cadherin causes loss of proper ganglion coalescence, similar to that observed after loss of Robo2, suggesting that the two pathways might intersect. Consistent with this possibility, blocking or augmenting Slit-Robo signaling modulates N-cadherin protein expression on the placodal cell surface concomitant with alteration in placodal adhesion. Lack of an apparent change in total N-cadherin mRNA or protein levels suggests post-translational regulation. Co-expression of N-cadherin with dominant-negative Robo abrogates the Robo2 loss-of-function phenotype of dispersed ganglia, whereas loss of N-cadherin reverses the aberrant aggregation induced by increased Slit-Robo expression. Our study suggests a novel mechanism whereby N-cadherin acts in concert with Slit-Robo signaling in mediating the placodal cell adhesion required for proper gangliogenesis

Incentives for Cost Reduction under Export Restraints. Incitations à l'innovation afin de réduire les coûts de production sous des restrictions quantitatives à l'importation..

The effect of trade quotas on firms’ incentive to invest in cost-reducing R&D is studied in a two-stage price-setting duopoly game. A domestic and a foreign firm first choose R&D levels and then set the prices of their differentiated products in the domestic market. With a quota imposed at, or close to, the free-trade level of imports, the domestic firm faces less competition than under free-trade and invests less in R&D. Contrarily, the constrained foreign firm invests more in R&D as the negative strategic effect of a reduction in its cost is now absent. These results differ partially from the Cournot duopoly case in which R&D expenditures are lower for both the firms. As the quota becomes more restrictive, the domestic firm increases and the foreign firm decreases its expenditures on R&D. Domestic welfare is always higher under free-trade than under any quota regardless of the degree of product substitutability.---------------------------------------------------------------------------Dans cet article, une firme nationale et une firme étrangère choisissent leurs niveaux de R&D dans un premier temps, puis fixent les prix de leurs produits différenciés sur le marché national. Si le quota imposé est égal ou est suffisamment proche du niveau des importations sous libre échange, la firme nationale investit moins en R&D. La firme étrangère contrainte investit plus, vu que l'effet stratégique négatif de la réduction des coûts par la R&D disparàît. On montre aussi que le niveau de bien-être national est toujours plus élevé sous libre échange indépendamment du degré de substituabilité des produits.

By and For Jewish Women Only: The Musical Film The Heart That Sings

The musical film, “The Heart that Sings” (2011), written and directed by Robin Saex Garbose, is part of a genre of films created by and for Orthodox Jewish women. Heart provides a case study that illustrates the depth and breadth of Lubavitch Rebbe Menachem Mendel Schneerson’s (1902-1994) influence on Jews and Jewish life well beyond his own community members. Schneerson’s outreach work via his shlichim, or emissaries, to unobservant Jews is well-recognized. The extent and nuance of his influence on a broad cross-section of Jews, however, has yet to be fully traced. Heart tells its viewers that Jewish women from all backgrounds can create an empowered, unified community, if religiously observant, Orthodox practices are in place, perpetuating Schneerson’s message with a feminist bent and musical twist

Short-time dynamics of finite-size mean-field systems

We study the short-time dynamics of a mean-field model with non-conserved order parameter (Curie-Weiss with Glauber dynamics) by solving the associated Fokker-Planck equation. We obtain closed-form expressions for the first moments of the order parameter, near to both the critical and spinodal points, starting from different initial conditions. This allows us to confirm the validity of the short-time dynamical scaling hypothesis in both cases. Although the procedure is illustrated for a particular mean-field model, our results can be straightforwardly extended to generic models with a single order parameter.Comment: accepted for publication in JSTA

IN VITRO AND IN VIVO REMOVAL OF ORAL ANTIDIABETIC AGENTS (METFORMIN) USING ACTIVATED CARBONS

Diabetes is the most worldwide common chronic disease, according the International Diabetes Federation [1], more than 32 million citizens living in the European Union have diabetes, representing nearly 10% of the population, to which we should add equal number of people suffering from impaired glucose tolerance. Diabetes prevalence is growing at alarming rate worldwide, being of particular relevance the type 2 diabetes. Nowadays 285 million people worldwide live with diabetes and it is expected that this numbers will increase by 20% until 2030 due to obesity and the ageing of the population [1]. This growth leads to an increasing consumption of drugs such as oral antidiabetics. Metformin is one of the active principles most commonly used for this purpose being among the pharmaceuticals with the highest production numbers worldwide to treat type 2 diabetes because is cheap, has high level of tolerance and when used in the prescribed dosage is very secure with minimal side effects. However, in case of overdose of metformin upon a ingestion of more than 10 times the prescribed dosage, accidentally or on propose, lactic acidosis and low blood pressure can occur. Overdoses with metformin are relatively uncommon, but may have serious consequences, if medical attention is not given on time, it may lead to coma and ultimately death Because of its spread use another problem must be taken into consideration, which needs to be addressed, the occurrence of metformin residues in sewage and surface waters due to improper discharge of the non-used tablets to regular garbage [2]. This situation is becoming a serious problem of environmental pollution and public health. This paper reports the use of activated carbon produced from biomass for the removal of metformin in 2 different settings. On one hand, from aqueous solutions and, in another hand, from simulated biological fluids (gastric and intestinal) conjugated with in vivo testing

The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin

BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. RESULTS: We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. CONCLUSION: The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection

Breaking arches with vibrations: the role of defects

We present experimental results about the stability of arches against external vibrations. Two dimensional strings of mutually stabilizing grains are geometrically analyzed and subsequently submitted to a periodic forcing at fixed frequency and increasing amplitude. The main factor that determines the granular arch resistance against vibrations is the maximum angle among those formed between any particle of the arch and its two neighbors: the higher the maximum angle is, the easier to break the arch. Based in an analysis of the forces, a simple explanation is given for this dependence. From this, interesting information can be extracted about the expected magnitudes of normal forces and friction coefficients of the particles conforming the arches

A tensor instability in the Eddington inspired Born-Infeld Theory of Gravity

In this paper we consider an extension to Eddington's proposal for the gravitational action. We study tensor perturbations of a homogeneous and isotropic space-time in the Eddington regime, where modifications to Einstein gravity are strong. We find that the tensor mode is linearly unstable deep in the Eddington regime and discuss its cosmological implications.Comment: 5 pages, approved by Phys. Rev. D, additional references and minor modification