1,720,972 research outputs found
A Novel Role for DNA Hydroxymethylation in Sexual Differentiation of the Mouse Brain
No full textFil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cortes, Laura R. Georgia State University. Neuroscience Institute; USA.Fil: Forger, Nancy G. Georgia State University. Neuroscience Institute; USA.Many sex differences in the brain are differences in neuronal phenotype (i.e., number of cells expressing a specific neurochemical marker). Epigenetic modifications, such as DNA methylation, control the development of cell phenotype throughout the body during embryogenesis, and sex differences in neurochemical cell phenotype could be due to differences in the control of DNA methylation. To test this, we first inhibited DNA methylation in the brains of newborn mice during the critical period of sexual differentiation. We found sex-specific effects (the inhibition of DNA methylation increased the number of calbindin-expressing cells only in females, and the number of estrogen receptor alpha cells only in males). As a result, sex differences were reduced or eliminated in the treated groups. We next hypothesized that DNA methylation during development depends on a balance between the addition of methyl groups (by DNA methyltransferases, DNMTs), and their removal (by ten-eleven translocases, Tets). Tet enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine. This is a first step to removal of the methyl mark, but hydroxymethylation is also emerging as a stable epigenetic mark in its own right, especially in the brain where it is found at much higher levels than in other tissues. We find that both DNMTs and Tets are expressed at even higher levels in the neonatal brain than at later ages, and that sex differences in expression are found only during the first postnatal week. Males have greater expression of Tet2 and Tet3 and lower expression of Dnmt1 in the preoptic area of the hypothalamus and this is associated with less 5mC in the same region. We are currently examining the effects of a transient downregulation in Tet enzymes to test for a causal relationship between Tet enzyme expression and sex differences in neuronal phenotype. Overall, our results suggest the novel idea that DNA de-methylation may primarily drive sex differences early in brain developmentFunding: This study was funded by a seed grant from the Brains & Behavior Program at Georgia State University.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Cortes, Laura R. Georgia State University. Neuroscience Institute; USA.Fil: Forger, Nancy G. Georgia State University. Neuroscience Institute; USA.Bioquímica y Biología Molecular (ídem 3.1.10
Effect of early life knock down of TETs on sex differences in cell type in the hypothalamus
No full textFil: Cortes, Laura R. Georgia State University. Neuroscience Institute; USA.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Golynker, Ilona. Georgia State University; Estados Unidos.Fil: Castillo-Ruiz, Alexandra. Georgia State University; Estados Unidos.Fil: Forger, Nancy G. Georgia State University. Neuroscience Institute; USA.One type of sex difference in the brain involves differences in the number of cells expressing a particular marker. For example, females have more cells expressing estrogen receptor alpha (ERa) in the ventrolateral region of the ventromedial nucleus of the hypothalamus (VMHvl), while males have more cells expressing calbindin in the sexually dimorphic nucleus of the preoptic area (CALB-SDN). DNA methylation and hydroxymethylation are crucial for the differentiation of neuronal cell phenotype during development, and we hypothesize that they may also play a role in the sexual differentiation of cell phenotype. To test this, we first treated newborn mice with zebularine, a global inhibitor of DNA methyl transferases (DNMTs). Zebularine treatment had a lasting effects on the number of cells expressing ERa and calbindin and reduced or eliminated sex differences in these markers (Mosley et al. 2019). DNA methylation and de-methylation are carried out by DNMTs (DNMT1, DNMT3b, and DNMT3a) and TET enzymes (TET1, TET2, TET3), respectively. We find that expression of these enzymes is much higher early in life compared to adulthood, and there are sex differences in the expression of all TETs and of DNMT1. To test whether these sex differences in enzyme expression underlie sex differences in cell phenotype, we used small interfering RNAs (siRNA) down-regulate DNMT1/DNMT3a or TET2/TET3. We found that injecting 2 microliters of 400pmol siRNA into the ventricles of male and female pups on P5 leads to a robust (~40%) down-regulation of expression compared to animals given control siRNA. Animals will be sacrificed at weaning and we will determine whether neonatal DNMT or TET knocknown alters the number of cells expressing ERa in the VMHvl and medial POA and calbindin in the SDN-POA and bed nucleus of the stria terminalis.https://www.sfn.org/meetings/neuroscience-2019Fil: Cortes, Laura R. Georgia State University. Neuroscience Institute; USA.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Odontología. Cátedra de Biología Celular; Argentina.Fil: Cisternas, Carla Daniela. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Fisiología Animal; Argentina.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina.Fil: Golynker, Ilona. Georgia State University; Estados Unidos.Fil: Castillo-Ruiz, Alexandra. Georgia State University; Estados Unidos.Fil: Forger, Nancy G. Georgia State University. Neuroscience Institute; USA.Bioquímica y Biología Molecular (ídem 3.1.10
Neonatal inhibition of DNA methylation disrupts testosterone-dependent masculinization of neurochemical phenotype
No full textMany neural sex differences are differences in the number of neurons of a particular phenotype. For example, male rodents have more calbindin-expressing neurons in the medial preoptic area (mPOA) and bed nucleus of the stria terminalis (BNST), and females have more neurons expressing estrogen receptor alpha (ERα) and kisspeptin in the ventromedial nucleus of the hypothalamus (VMH) and the anteroventral periventricular nucleus (AVPV), respectively. These sex differences depend on neonatal exposure to testosterone, but the underlying molecular mechanisms are unknown. DNA methylation is important for cell phenotype differentiation throughout the developing organism. We hypothesized that testosterone causes sex differences in neurochemical phenotype via changes in DNA methylation, and tested this by inhibiting DNA methylation neonatally in male and female mice, and in females given a masculinizing dose of testosterone. Neonatal testosterone treatment masculinized calbindin, ERα and kisspeptin cell number of females at weaning. Inhibiting DNA methylation with zebularine increased calbindin cell number only in control females, thus eliminating sex differences in calbindin in the mPOA and BNST. Zebularine also reduced the sex difference in ERα cell number in the VMH, in this case by increasing ERα neuron number in males and testosterone-treated females. In contrast, the neonatal inhibition of DNA methylation had no effect on kisspeptin cell number. We conclude that testosterone normally increases the number of calbindin cells and reduces ERα cells in males through orchestrated changes in DNA methylation, contributing to, or causing, the sex differences in both cell types.Fil: Cisternas, Carla Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cortese, Maria Laura. Georgia State University; Estados UnidosFil: Golynker, Ilona. Georgia State University; Estados UnidosFil: Castillo-Ruiz, Alexandra. Georgia State University; Estados UnidosFil: Forger, Nancy G.. Georgia State University; Estados Unido
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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