Measuring Security Price Performance Using Chilean Daily Stock Returns: The event Study Method

24 p.Siguiendo el enfoque de simulación de Brown y Warner y usando retornos diarios del mercado accionario chileno,examinamos la especificación y el poder de tres estadísticos comúnmente utilizados en estudios de evento: el test estandarizado,el de corte transversal y el de portfolio. Nuestros resultados muestran que aunque los retornos y excesos de retornos a nivel individual evidentemente no distribuyen normal, la media muestral converge hacia la normalidad en la medida que el número de acciones del portfolio muestral aumenta. Así, las pruebas estadísticas típicamente utilizadas en estudios de evento de un día estarían bien especificadas, al menos para un nivel de significancia del 5%. En términos del poder del test, el test estandarizado siempre se muestra más poderoso para capturar la presencia de un retorno anormal que sus dos competidores: el test de corte transversal y el de portfolio. También encontramos, sin embargo, que el poder de las tres pruebas estadísticas analizadas es muy sensible tanto al tamaño muestral como al número de días que involucre el evento

B-Function Expression in the Flower Center Underlies the Homeotic Phenotype of Lacandonia schismatica (Triuridaceae)

Spontaneous homeotic transformations have been described in natural populations of both plants and animals, but little is known about the molecular-genetic mechanisms underlying these processes in plants. In the ABC model of floral organ identity in Arabidopsis thaliana, the B- and C-functions are necessary for stamen morphogenesis, and C alone is required for carpel identity. We provide ABC model-based molecular-genetic evidence that explains the unique inside-out homeotic floral organ arrangement of the monocotyledonous mycoheterotroph species Lacandonia schismatica (Triuridaceae) from Mexico. Whereas a quarter million flowering plant species bear central carpels surrounded by stamens, L. schismatica stamens occur in the center of the flower and are surrounded by carpels. The simplest explanation for this is that the B-function is displaced toward the flower center. Our analyses of the spatio-temporal pattern of B- and C-function gene expression are consistent with this hypothesis. The hypothesis is further supported by conservation between the B-function genes of L. schismatica and Arabidopsis, as the former are able to rescue stamens in Arabidopsis transgenic complementation lines, and Ls-AP3 and Ls-PI are able to interact with each other and with the corresponding Arabidopsis B-function proteins in yeast. Thus, relatively simple molecular modifications may underlie important morphological shifts in natural populations of extant plant taxa

Demographic fitness of Belminus ferroae (Hemiptera: Triatominae) on three different hosts under laboratory conditions

Triatominae are widely recognised for their role as vectors of Trypanosoma cruzi. One of the main biological characteristics of this subfamily is their obligate haematophagous condition. However, previous studies on Belminus herreri and Belminus ferroae suggested that cockroaches are their principal hosts in domiciles. Due to this peculiar behaviour, the aim of this study was to analyse several demographic and reproductive parameters of B. ferroae fed on three different hosts (mice, cockroaches and Rhodnius prolixus) and relate B. ferroae fitness to these alternative hosts. The cohorts were reared under constant conditions. The egg hatching rate was similar for cohorts fed on cockroaches (69.4%) and R. prolixus (63.8%), but was much lower for the cohort fed on mice (16%). The development time from the nymph to adult stage and the average age of first reproduction (α) presented lower values in the cohort fed on cockroaches, which is consistent with the higher population growth rate associated with this host. Demographic parameters [intrinsic rate of natural increase, finite rate of population growth, net reproductive rate and damping ratio] showed statistically significant differences between the cohorts. Analysis of the life history of B. ferroae revealed a higher fitness related to the cockroach. The implications of these results for the origin of the subfamily are discussed.Centro de Estudios Parasitológicos y de Vectore

Demographic fitness of Belminus ferroae (Hemiptera: Triatominae) on three different hosts under laboratory conditions

Triatominae are widely recognised for their role as vectors of Trypanosoma cruzi. One of the main biological characteristics of this subfamily is their obligate haematophagous condition. However, previous studies on Belminus herreri and Belminus ferroae suggested that cockroaches are their principal hosts in domiciles. Due to this peculiar behaviour, the aim of this study was to analyse several demographic and reproductive parameters of B. ferroae fed on three different hosts (mice, cockroaches and Rhodnius prolixus) and relate B. ferroae fitness to these alternative hosts. The cohorts were reared under constant conditions. The egg hatching rate was similar for cohorts fed on cockroaches (69.4%) and R. prolixus (63.8%), but was much lower for the cohort fed on mice (16%). The development time from the nymph to adult stage and the average age of first reproduction (α) presented lower values in the cohort fed on cockroaches, which is consistent with the higher population growth rate associated with this host. Demographic parameters [intrinsic rate of natural increase, finite rate of population growth, net reproductive rate and damping ratio] showed statistically significant differences between the cohorts. Analysis of the life history of B. ferroae revealed a higher fitness related to the cockroach. The implications of these results for the origin of the subfamily are discussed.Centro de Estudios Parasitológicos y de Vectore

Glutamate and Brain Glutaminases in Drug Addiction

Glutamate is the principal excitatory neurotransmitter in the central nervous system and its actions are related to the behavioral effects of psychostimulant drugs. In the last two decades, basic neuroscience research and preclinical studies with animal models are suggesting a critical role for glutamate transmission in drug reward, reinforcement, and relapse. Although most of the interest has been centered in post-synaptic glutamate receptors, the presynaptic synthesis of glutamate through brain glutaminases may also contribute to imbalances in glutamate homeostasis, a key feature of the glutamatergic hypothesis of addiction. Glutaminases are the main glutamate-producing enzymes in brain and dysregulation of their function have been associated with neurodegenerative diseases and neurological disorders; however, the possible implication of these enzymes in drug addiction remains largely unknown. This mini-review focuses on brain glutaminase isozymes and their alterations by in vivo exposure to drugs of abuse, which are discussed in the context of the glutamate homeostasis theory of addiction. Recent findings from mouse models have shown that drugs induce changes in the expression profiles of key glutamatergic transmission genes, although the molecular mechanisms that regulate drug-induced neuronal sensitization and behavioral plasticity are not clear.This work was financially supported by Grants RD12/0028/0013 (JM) and RD12/0028/0001 (FRF) of the RTA RETICS network from the Spanish Health Institute Carlos III, Grant SAF2015-64501-R from the Spanish Ministry of Economy and Competitivity (to JM and JMM) and Excellence Grant CVI-6656 (Regional Andalusian government) (to JM)

Demographic fitness of Belminus ferroae (Hemiptera: Triatominae) on three different hosts under laboratory conditions

Triatominae are widely recognised for their role as vectors of Trypanosoma cruzi. One of the main biological characteristics of this subfamily is their obligate haematophagous condition. However, previous studies on Belminus herreri and Belminus ferroae suggested that cockroaches are their principal hosts in domiciles. Due to this peculiar behaviour, the aim of this study was to analyse several demographic and reproductive parameters of B. ferroae fed on three different hosts (mice, cockroaches and Rhodnius prolixus) and relate B. ferroae fitness to these alternative hosts. The cohorts were reared under constant conditions. The egg hatching rate was similar for cohorts fed on cockroaches (69.4%) and R. prolixus (63.8%), but was much lower for the cohort fed on mice (16%). The development time from the nymph to adult stage and the average age of first reproduction (α) presented lower values in the cohort fed on cockroaches, which is consistent with the higher population growth rate associated with this host. Demographic parameters [intrinsic rate of natural increase, finite rate of population growth, net reproductive rate and damping ratio] showed statistically significant differences between the cohorts. Analysis of the life history of B. ferroae revealed a higher fitness related to the cockroach. The implications of these results for the origin of the subfamily are discussed.Centro de Estudios Parasitológicos y de Vectore

Ratones knock-out del receptor lpa1 de ácido lisofosfatídico presentan un acusado déficit de la isoenzima glutaminasa KGA (GLS) y una morfología alterada en las espinas dendríticas de hipocampo y corteza

Objectives: The objective of the present study was to utilize mice with knocked-down lysophosphatidic acid 1 (LPA1) receptor to ascertain changes in glutamatergic transmission that may help to explain part of the cognitive and memory deficits shown by these KO-LPA1 mice. Material & methods: A well characterized KO-LPA1 mouse strain was used as animal model and compared with wild-type (WT) and heterozygous animals. Expression studies were implemented by immunohistochemistry and Western analysis of mouse brain regions, real-time quantitative RT-PCR of GA isoforms, enzymatic analysis of regional GA activity and Golgi staining to assess dendritic spine morphology and density. Results: A strong reduction of KGA immunoreactivity was mostly revealed in cerebral cortex and hippocampus of KO-LPA1 mice versus WT and heterozygous animals. In contrast, neither mRNA levels nor enzyme activity were significantly altered in KO mice suggesting compensatory mechanisms for neurotransmitter Glu synthesis. Interestingly, Golgi staining of hippocampal and cortical neurons revealed a clear morphology change toward a less-mature undifferentiated spine phenotype, without changes in the total number of spines. Conclusions: The molecular mechanisms underlying KGA downregulation in null LPA1 mutant mice are unknown. However, LPA increases neuronal differentiation, arborization and neurite outgrowth of developing neurons, while Gln-derived Glu, through GA reaction, has been also involved in neuronal growth and differentiation. It is tempting to speculate that downregulation of KGA protein in KO-LPA1 mice induce morphological changes in dendritic spines of cortical and hippocampal neurons which, in turn, may account for memory and cognitive deficits shown by KO-LPA1 mice.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Acknowledgements: Red de Trastornos Adictivos, RTA, (RD12/0028/0013/) RETICS, ISCIII, y Consejería Innovación, Ciencia y Empresa, Junta de Andalucía (Proyecto de Excelencia CVI-6656)

Glutaminase and MMP-9 downregulation in cortex and hippocampus of LPA1 receptor null mice correlate with altered dendritic spine plasticity

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus. Immunohistochemical assessment of protein levels for the second type of glutaminase (GA) isoform, glutaminase gene encoding the liver-type isoforms (GLS2), did not detect substantial differences with regard to WT animals. The regional mRNA levels of GLS were determined by real time RT-PCR and did not show significant variations, except for prefrontal and motor cortex values which clearly diminished in KO mice. Total GA activity was also significantly reduced in prefrontal and motor cortex, but remained essentially unchanged in the hippocampus and rest of brain regions examined, suggesting activation of genetic compensatory mechanisms and/or post-translational modifications to compensate for KGA protein deficit. Remarkably, Golgi staining of hippocampal regions showed an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature filopodia-like phenotype, as compared with WT littermates. This structural change correlated with a strong decrease of active matrix-metalloproteinase (MMP) 9 in cerebral cortex and hippocampus of KOLPA1 mice. Taken together, these results demonstrate that LPA signaling through LPA1 influence expression of the main isoenzyme of glutamate biosynthesis with strong repercussions on dendritic spines maturation, which may partially explain the cognitive and learning defects previously reported for this colony of KOLPA1 mice

Identification of novel synthetic lethal vulnerability in non small cell lung cancer by co targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4