Atypical RhoV and RhoU GTPases control development of the neural crest

This review addresses the developmental roles of two GTPases of the Rho family, RhoV/Chp and RhoU/Wrch. These two GTPases form a distinct subfamily related to Rac and Cdc42 proteins and were detected in a screen for Rho members that are particularly expressed in the neural crest, an embryonic tissue peculiar to vertebrates. The neural crest represents a physiological model of normal epithelial to mesenchymal transition (EMT), in which epithelial cells at the border of neural and non-neural ectoderm differentiate, lose their intercellular connections and migrate throughout the embryo. We showed that RhoV, transiently induced by the canonical Wnt pathway, is required for the full differentiation of neural crest cells, while RhoU, induced later by the non-canonical Wnt pathway, is necessary for the migration process. These two GTPases, which are highly conserved across vertebrates, are thus tightly functionally linked to Wnt signaling, whose implication in embryonic development and cancer progression is well established. In the light of the recent literature, we discuss how RhoV and RhoU may achieve their physiological functions

No strings attached: New insights into epithelial morphogenesis

The dramatic ingression of tissue sheets that accompanies many morphogenetic processes, most notably gastrulation, has been largely attributed to contractile circum-apical actomyosin 'purse-strings' in the infolding cells. Recent studies, however, including one in BMC Biology, expose mechanisms that rely less on actomyosin contractility of purse-string bundles and more on dynamics in the global cortical actomyosin network of the cells. These studies illustrate how punctuated actomyosin contractions and flow of these networks can remodel both epithelial and planarly organized mesenchymal sheets. © 2012 Davidson; licensee BioMed Central Ltd

The Role of Voltage-Gated Calcium Channels in Neurotransmitter Phenotype Specification: Coexpression and Functional Analysis in Xenopus laevis

Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage-gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity-dependent neurotransmitter phenotype specification. To test this hypothesis, multiplex fluorescent in situ hybridization was used to characterize the coexpression of eight VGCC alpha 1 subunits with the excitatory and inhibitory neural markers xVGlut1 and xVIAAT in Xenopus laevis embryos. VGCC coexpression was higher with xVGlut1 than xVIAAT, especially in the hindbrain, spinal cord, and cranial nerves. Calcium activity was also analyzed on a single-cell level, and spike frequency was correlated with the expression of VGCC alpha 1 subunits in cell culture. Cells expressing Ca(V)2.1 and Ca(V)2.2 displayed increased calcium spiking compared with cells not expressing this marker. The VGCC antagonist diltiazem and agonist (-)BayK 8644 were used to manipulate calcium activity. Diltiazem exposure increased the number of glutamatergic cells and decreased the number of gamma-aminobutyric acid (GABA)ergic cells, whereas (2) BayK 8644 exposure decreased the number of glutamatergic cells without having an effect on the number of GABAergic cells. Given that the expression and functional manipulation of VGCCs are correlated with neurotransmitter phenotype in some, but not all, experiments, VGCCs likely act in combination with a variety of other signaling factors to determine neuronal phenotype specification. (C) 2014 Wiley Periodicals, Inc

Transitory activation of AMPK at reperfusion protects the ischaemic-reperfused rat myocardium against infarction

PURPOSE: AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size. METHODS: Perfused rat hearts were subjected to 35 min ischaemia and 120 min reperfusion. Metformin (50 microM) or AICAR (0.5 mM) were added for 15 min at the onset of reperfusion alone or with Compound C (CC, 10 microM), an AMPK inhibitor. Infarct size and alpha-AMPK phosphorylation were measured. RESULTS: Metformin significantly reduced infarct size from 47.8 +/- 1.7% in control to 31.4 +/- 2.9%, an effect abolished by CC when the drugs were given concomitantly. Similarly, AICAR also induced a significant reduction in infarct size to 32.3 +/- 4.8%, an effect also abrogated by CC. However, metformin's protection was not abolished if CC was administered later in reperfusion. In addition, alpha-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion. CONCLUSIONS: Our data demonstrated that, in our ex vivo model of myocardial ischaemia-reperfusion injury, AMPK activation in early reperfusion is associated with a reduction in infarct size

Wormhole solutions in the Randall-Sundrum scenario

In the simplest form of the Randall-Sundrum model, we consider the metric generated by a static, spherically symmetric distribution of matter on the physical brane. The solution to the five-dimensional Einstein equations, obtained numerically, describes a wormhole geometry.Comment: 10 pages, 2 figures, revtex

Revisiting 2D Numerical Models for the 19th century outbursts of η\eta Carinae

We present here new results of two-dimensional hydrodynamical simulations of the eruptive events of the 1840s (the great) and the 1890s (the minor) eruptions suffered by the massive star $\eta$ Car. The two bipolar nebulae commonly known as the Homunculus and the little Homunculus were formed from the interaction of these eruptive events with the underlying stellar wind. As in previous work (Gonzalez et al. 2004a, 2004b), we assume here an interacting, nonspherical multiple-phase wind scenario to explain the shape and the kinematics of both Homunculi, but adopt a more realistic parametrization of the phases of the wind. During the 1890s eruptive event, the outflow speed {\it decreased} for a short period of time. This fact suggests that the little Homunculus is formed when the eruption ends, from the impact of the post-outburst $\eta$ Car wind (that follows the 1890s event) with the eruptive flow (rather than by the collision of the eruptive flow with the pre-outburst wind, as claimed in previous models; Gonzalez et al. 2004a, 2004b). Our simulations reproduce quite well the shape and the observed expansion speed of the large Homunculus. The little Homunculus (which is embedded within the large Homunculus) becomes Rayleigh-Taylor unstable and develop filamentary structures that resembles the spatial features observed in the polar caps. In addition, we find that the interior cavity between the two Homunculi is partially filled by material that is expelled during the decades following the great eruption. This result may be connected with the observed double-shell structure in the polar lobes of the $\eta$ Car nebula. Finally, as in previous work, we find the formation of tenuous, equatorial, high-speed features that seem to be related to the observed equatorial skirt of $\eta$ Car.Comment: accepted for publication in MNRA

Geometrical features of (4+d) gravity

We obtain the vacuum spherical symmetric solutions for the gravitational sector of a (4+d)-dimensional Kaluza-Klein theory. In the various regions of parameter space, the solutions can describe either naked singularities or black-holes or wormholes. We also derive, by performing a conformal rescaling, the corresponding picture in the four-dimensional space-time.Comment: 10 pages, LateX2e, to appear in Phys.Rev.

The economic case for investing in the prevention of mental health conditions in the UK

This report provides an overview of the economic case for the prevention of mental health conditions. To do this, we first estimated the societal costs of living with mental health conditions in the UK in 2019 and then reviewed what is known about the cost-effectiveness of wellevidenced actions to prevent these mental health conditions. To estimate costs, we used a prevalencebased costing approach. This measures the number of people living with mental health conditions over a specific short time period (usually one year) and estimates the average costs associated with these conditions over this time period. Our prevalencebased costing model makes use of data on prevalence from the 2019 Institute of Health Metrics and Evaluation Global Burden of Disease (GBD) study. The GBD study quantifies the impact of all health conditions, both infectious and non-communicable, including mental health conditions, as well as the impacts on injury, including intentional self-harm. As part of the study, the GBD systematically searches for and assesses mental health surveys around the globe. To allow for comparability in measurement, case definitions used by GBD predominantly adhered to international diagnostic criteria guidance, either the DSM-IV-TR, mainly used in the United States or the ICD-10 criteria used mainly elsewhere, as these are used by the majority of mental health surveys included in the GBD. The GBD study estimates are periodically updated, apply a common methodology, are subject to peer review, and are routinely used by the World Health Organization (WHO) when looking at the global impact of mental health conditions. Furthermore, GBD estimates are provided separately for all four nations of the UK, as well as at English Region level. These estimates are conservative, as the GBD does not include the impact of sub-diagnostic threshold mental health conditions, as well as risk factors such as undue stress which do not fit into diagnostic criteria, all of which will also have economic costs. We included 11 of 12 broad categories of mental disorder meeting diagnosable thresholds used in the GBD1. These were depressive disorders (major depressive disorder and dysthymia), anxiety disorders, bipolar affective disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder (ADHD), eating disorders (anorexia nervosa and bulimia nervosa), and a final category of other mental disorders (which mainly covers personality disorders). A detailed list of conditions is listed in Table A-2 in the appendix. We excluded the idiopathic intellectual disabilities category in the GBD. Neurological conditions such as dementia, as well as alcohol and substance use disorders, are not included. Although not all intentional self-harm is linked with a mental health condition, we also separately provide an estimate of the health and intangible costs associated with intentional self-harm, including suicide, reported in the GBD. All costs are calculated and reported in 2020 pounds sterling

Millimeter length micromachining using a heavy ion nuclear microprobe with standard magnetic scanning

In order to increase the scanning length of our microprobe, we have developed an irradiation procedure suitable for use in any nuclear microprobe, extending at least up to 400% the length of our heavy ion direct writing facility using standard magnetic exploration. Although this method is limited to patterns of a few millimeters in only one direction, it is useful for the manufacture of curved waveguides, optical devices such Mach-Zehnder modulators, directional couplers as well as channels for micro-fluidic applications. As an example, this technique was applied to the fabrication of 3mm 3D-Mach-Zehnder modulators in lithium niobate with short Y input/output branches and long shaped parallel-capacitor control electrodes. To extend and improve the quality of the machined structures we developed new scanning control software in LabViewTM platform. The new code supports an external dose normalization, electrostatic beam blanking and is capable of scanning figures at 16 bit resolution using a National InstrumentsTM PCI-6731 High-Speed I/O card. A deep and vertical micromachining process using swift 35Cl ions 70 MeV bombarding energy and direct write patterning was performed on LiNbO3, a material which exhibits a strong natural anisotropy to conventional etching. The micromachined structures show the feasibility of this method for manufacturing micro-fluidic channels as well.Fil: Nesprias, Francisco Jose Gabriel. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Debray, Mario Ernesto. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; ArgentinaFil: Davidson, Jorge. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kreiner, Andres Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; ArgentinaFil: Vega, Nahuel Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; ArgentinaFil: de la Fourniere, Emanuel María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes. Gerencia de Investigación y Aplicaciones; Argentin