Congenital anomalies from a physics perspective. The key role of "manufacturing" volatility

Genetic and environmental factors are traditionally seen as the sole causes of congenital anomalies. In this paper we introduce a third possible cause, namely random "manufacturing" discrepancies with respect to ``design'' values. A clear way to demonstrate the existence of this component is to ``shut'' the two others and to see whether or not there is remaining variability. Perfect clones raised under well controlled laboratory conditions fulfill the conditions for such a test. Carried out for four different species, the test reveals a variability remainder of the order of 10%-20% in terms of coefficient of variation. As an example, the CV of the volume of E.coli bacteria immediately after binary fission is of the order of 10%. In short, ``manufacturing'' discrepancies occur randomly, even when no harmful mutation or environmental factors are involved. Not surprisingly, there is a strong connection between congenital defects and infant mortality. In the wake of birth there is a gradual elimination of defective units and this screening accounts for the post-natal fall of infant mortality. Apart from this trend, post-natal death rates also have humps and peaks associated with various inabilities and defects.\qL In short, infant mortality rates convert the case-by-case and mostly qualitative problem of congenital malformations into a global quantitative effect which, so to say, summarizes and registers what goes wrong in the embryonic phase. Based on the natural assumption that for simple organisms (e.g. rotifers) the manufacturing processes are shorter than for more complex organisms (e.g. mammals), fewer congenital anomalies are expected. Somehow, this feature should be visible on the infant mortality rate. How this conjecture can be tested is outlined in our conclusion.Comment: 43 pages, 9 figure

Towards Nonlinear Photonic Wires in Z-cut LiNbO3

International audienceUsing a modified Proton Exchange process we have realized Photonic Wires in X-cut LiNbO3. They exhibit highly confined mode, low propagation losses, low strain induced polarization coupling and no reduction of the nonlinear properties. We are now transferring this technique to Z-cut LiNbO3 in order to realize very efficient nonlinear devices in PPLN

The thermal equation of state of FeTiO_3 ilmenite based on in situ X-ray diffraction at high pressures and temperatures

We present in situ measurements of the unit-cell volume of a natural terrestrial ilmenite (Jagersfontein mine, South Africa) and a synthetic reduced ilmenite (FeTiO_3) at simultaneous high pressure and high temperature up to 16 GPa and 1273 K. Unit-cell volumes were determined using energy-dispersive synchrotron X-ray diffraction in a multi-anvil press. Mössbauer analyses show that the synthetic sample contained insignificant amounts of Fe^(3+) both before and after the experiment. Results were fit to Birch-Murnaghan thermal equations of state, which reproduce the experimental data to within 0.5 and 0.7 GPa for the synthetic and natural samples, respectively. At ambient conditions, the unit-cell volume of the natural sample [V_0 = 314.75 ± 0.23 (1 ) Å^3] is significantly smaller than that of the synthetic sample [V_0 = 319.12 ± 0.26 Å^3]. The difference can be attributed to the presence of impurities and Fe^(3+) in the natural sample. The 1 bar isothermal bulk moduli K_(T0) for the reduced ilmenite is slightly larger than for the natural ilmenite (181 ± 7 and 165 ± 6 GPa, respectively), with pressure derivatives K_0' = 3 ± 1. Our results, combined with literature data, suggest that the unit-cell volume of reduced ilmenite is significantly larger than that of oxidized ilmenite, whereas their thermoelastic parameters are similar. Our data provide more appropriate input parameters for thermo-chemical models of lunar interior evolution, in which reduced ilmenite plays a critical role

Modes Hybrides dans les Fils Quantiques Réalisés sur Niobate de Lithium en Coupe X

Dans ce papier, nous nous concentrerons sur l'influence des contraintes induites dans le cristal par le processus de fabrication des fils quantiques. Ces tensions sont responsables d'un couplage fort entre les polarisations qui confère une nature hybride aux modes se propageant et qui doit être prise en considération dans la conception des dispositifs

Glucocorticoids and neurodegeneration

Series: Endocrinology research and clinical developmentsGlucocorticoids (GCs) exert wide-spread actions in central nervous system ranging from gene transcription, cellular signaling, modulation of synaptic structure and transmission, glial responses to altered neuronal circuitry and behavior through the activation of two steroid hormone receptors, glucocorticoid receptor (NR3C1, GR) and mineralocorticoid receptor (NR3C2, MR). These highly-related receptors exert both genomic and non-genomic actions in the brain, which are context-dependent and essential for adaptive responses to stress resulting in modulations of behavior, learning and memory processes. Thus, GCs through their receptors are implicated in neural plasticity as they modulate the dendritic and synaptic structure of neurons as well as the survival and fate of newly-generated cells (neuro- and glio-genesis) in adult brain. GCs are also important in fetal brain programming as inappropriate variations in their levels during critical developmental periods are suggested to be casually related to the development of brain pathologies and maladaptive responses of hypothalamic-pituitary adrenal (HPA) axis to stress during adulthood. They regulate immune responses in brain, which have important consequences for neuronal survival. In situations of chronic stress and HPA axis dysfunction resulting in chronically high or low GCs levels, a multitude of molecular, structural and functional changes occur in the brain, eventually leading to maladaptive behavior. In fact, clinical studies suggest a causal relation of deregulated GC responses with development of neurodegenerative disorders such as Alzheimer´s (AD) and Parkinson‘s (PD) diseases. AD and PD patients have high levels of circulating cortisol while animal studies suggest that this chronic GC elevation participates in neurodegenerative processes in both AD and PD pathologies. This chapter will focus on the role of HPA axis and GCs on neurodegenerative processes involved in AD and PD pathogenesis.(undefined

Chronic stress and glucocorticoids: from neuronal plasticity to neurodegeneration

Stress and stress hormones, glucocorticoids (GCs), exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's (PD) diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.The work was supported by Grants “PTDC/SAU-NMC/113934/2009,” funded by FCT, Portuguese Foundation for Science and Technology, and project DoIT, Desenvolvimento e Operacionalização da Investigação de Translação (N° do projeto 13853), funded by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Programa Operacional Fatores de Competitividade (POFC). In addition, this work was also cofinanced by European Union FP7 Project SwitchBox (Nuno Sousa, Osborne F. X. Almeida) and the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). Sheela Vyas acknowledges grant support from Foundation de France, Physiopathology of Parkinson, France Parkinson and ANR Grant “ParkStrim” N° 13-BSV1-0013-02. Work in FT research group was supported by Agence Nationale de la Recherche (TIMMS and StressPsyco) and Fondation pour la Recherche Médicale, Grant no. DEQ20140329552

MicroRNA-9 controls dendritic development by targeting REST

MicroRNAs (miRNAs) are conserved noncoding RNAs that function as posttranscriptional regulators of gene expression. miR-9 is one of the most abundant miRNAs in the brain. Although the function of miR-9 has been well characterized in neural progenitors, its role in dendritic and synaptic development remains largely unknown. In order to target miR-9 in vivo, we developed a transgenic miRNA sponge mouse line allowing conditional inactivation of the miR-9 family in a spatio-temporal-controlled manner. Using this novel approach, we found that miR-9 controls dendritic growth and synaptic transmission in vivo. Furthermore, we demonstrate that miR-9-mediated downregulation of the transcriptional repressor REST is essential for proper dendritic growth.Fil: Giusti, Sebastian Alejandro. Max Planck Institute of Psychiatry; AlemaniaFil: Vogl, Annette M.. Max Planck Institute of Psychiatry; AlemaniaFil: Brockmann, Marina M.. Max Planck Institute of Psychiatry; AlemaniaFil: Vercelli, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Rein, Martin L.. Max Planck Institute of Psychiatry; AlemaniaFil: Trümbach, Dietrich. Helmholtz Zentrum München; AlemaniaFil: Wurst, Wolfgang. Helmholtz Zentrum München; AlemaniaFil: Cazalla, Demian. University of Utah; Estados UnidosFil: Stein, Valentin. Universitaet Bonn; AlemaniaFil: Deussing, Jan M.. Max Planck Institute of Psychiatry; AlemaniaFil: Refojo, Damian. Max Planck Institute of Psychiatry; Alemani

A novel TaulacZ allele reveals a requirement for Pitx2 in formation of the mammillothalamic tract

The hypothalamic mammillary region is critical for spatial memory and vestibular processing. Pitx2 encodes a paired‐like transcription factor that is highly expressed in the developing mammillary region and is required for subthalamic nucleus formation. Here we analyzed a loss of function Pitx2 ‐ TaulacZ knock‐in allele to study the effects of Pitx2 deficiency on neuronal projections in the embryonic mammillary region. Pitx2 ‐expressing neurons contribute axons to principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are improperly bundled and disorganized, yet project caudally toward the tectum and tegmentum. Embryos with Nestin‐Cre mediated conditional Pitx2 deficiency exhibit truncated mammillothalamic tracts (mtt) that fail to elongate, and reduced Pax6 ‐positive cells at the branching point of the principal mammillary and mtt. These data suggest that Pitx2 mediates cell‐autonomous and nonautonomous guidance cues necessary for mammillary collaterals destined to project to the anterior thalamus. genesis 50:67–73, 2012. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90263/1/20793_ftp.pd