Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence

[Abstract] Introduction: Gender incongruence defines a state in which individuals feel discrepancy between the sex assigned at birth and their gender. Some of these people make a social transition from male to female (transwomen) or from female to male (trans men). By contrast, the word cisgender describes a person whose gender identity is consistent with their sex assigned at birth. Aim: To analyze the implication of the estrogen receptor a gene (ESR1) in the genetic basis of gender incongruence. Main Outcome Measures: Polymorphisms rs9478245, rs3138774, rs2234693, rs9340799. Method: We carried out the analysis of 4 polymorphisms located at the promoter of the ESR1 gene (C1 ¼ rs9478245, C2 ¼ rs3138774, C3 ¼ rs2234693, and C4 ¼ rs9340799) in a population of 273 trans women, 226 trans men, and 537 cis gender controls. For SNP polymorphisms, the allele and genotype frequencies were analyzed by c2 test. The strength of the SNP associations with gender incongruence was measured by binary logistic regression. For the STR polymorphism, the mean number of repeats were analyzed by the ManneWhitney U test. Measurement of linkage disequilibrium and haplotype frequencies were also performed. Results: The C2 median repeats were shorter in the trans men population. Genotypes S/S and S/L for the C2 polymorphism were overrepresented in the trans men group (P ¼ .012 and P ¼ .003 respectively). We also found overtransmission of the A/A genotype (C4) in the trans men population (P ¼ .017), while the A/G genotype (C4) was subrepresented (P ¼ .009]. The analyzed polymorphisms were in linkage disequilibrium. In the trans men population, the T(C1)-L(C2)-C(C3)-A(C4) haplotype was overrepresented (P ¼ .019) while the T(C1)-L(C2)-C(C3)-G(C4) was subrepresented (P ¼ .005). Conclusion: The ESR1 is associated with gender incongruence in the trans men populationThis work was supported by grants: ED431B 019/02 (EP), PGC2018-094919-B-C21 (AG), PGC2018-094919-B-C22 (RF), and FPU 15/02558 (JCC)Xunta de Galicia; ED431B 019/0

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

[Abstract] Background Brain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. Aim To analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. Methods We carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. Outcomes The main outcome of this study was RIII analysis using bisulfite genomic sequencing. Results We found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P ≤ .003, P ≤ .026, P ≤ .001, P ≤ .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P ≤ .0001, P ≤ .018, P ≤ .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical Implications Clinical implications in the hormonal treatment of trans people. Strengths & Limitations Increasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. Conclusions Our data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and transmen showed a characteristic methylation profile, different from both the cisgender groups. But the hormonal treatment modified RIII methylation in trans populations, which are now more similar to their gender. Therefore, our results suggest that the methylation of RIII could be involved in gender dysphoria.This work was supported by grants: Xunta de Galicia ED431 B 019/02 (EP), PGC2018-094919-B-C21 (AG), Ministerio de ciencia, innovación y Universidades PGC2018-094919-B-C22 (RF, EP). J. Cortés-Cortés was supported by a doctoral fellowship FPU 15/02558Xunta de Galicia ED431 B 019/0

Superconducting density of states and band structure at the surface of the candidate topological superconductor Au2 Pb

The electronic band structure of Au2Pb has a Dirac cone which gaps when undergoing a structural transition into a low temperature superconducting phase. This suggests that the superconducting phase (Tc = 1.1 K) might hold topological properties at the surface. Here we make Scanning Tunneling Microscopy experiments on the surface of superconducting Au2Pb. We measure the superconducting gap and find a sizable superconducting density of states at the Fermi level. We discuss possible origins for this finding in terms of superconductivity induced into surface state

Analysis of the development of the forgetfulness curve within a program of training in Basic Life Support for students of the Degree of Medicine from de University of granada. Pilot study.

Objetivo: El objetivo del estudio es analizar la curva del olvido en el aprendizaje del Soporte Vital Básico en estudiantes de medicina de la Universidad de Granada. Material y métodos: Se trata de un estudio observacional, descriptivo transversal, que establece como población diana a los estudiantes de Grado de Medicina de la Universidad de Granada que cursan cuarto y quinto curso. Periodo de estudio comprendido entre octubre de 2015 y enero de 2017.Se emplearon los datos obtenidos en una evaluación inicial que se realizó en la Facultad de Medicina, y los de una reevaluación que se les realizó a una muestra de cada uno de los cursos. Se incluyeron en el estudio de forma voluntaria todos los alumnos matriculados en la asignatura bases de la medicina interna II para cada uno de los cursos académicos. El análisis se realizó utilizando medidas de tendencia central, tablas de frecuencias y posteriormente se realizó un análisis estadístico mediante la Prueba T de Student. Resultados: Los alumnos de cuarto consiguieron una media en la primera evaluación de 13,91 sobre 15 puntos, mientras que en la segunda la media fue de 13,81. Por otro lado, los alumnos de quinto consiguieron una media de 13,80 en la primera evaluación y una de 13,18 en la reevaluación. Estos datos nos hablan de que, a pesar de que los cursos resultaron muy satisfactorios en ambos cursos, encontramos un mayor impacto de la curva del olvido en alumnos que llevan más tiempo sin realizar un reciclaje en Soporte Vital Básico. Conclusiones: A pesar de existir una disminución de los conocimientos y habilidades relacionados con la práctica del soporte vital al año de recibir la formación específica en ambos grupos, no existen diferencias estadísticamente significativas para los sujetos de nuestro grupo que obliguen a establecer programas de reciclaje entre seis y nueve meses como establecen las recomendaciones actuales. A la luz de nuestro estudio, recomendamos el desarrollo de programas específicos de reciclaje en períodos de tiempo superiores a los doce meses después de recibir la formación inicial.Aim: The aim of this study was to analyze the oblivion curve after the learning of Basic Life Support (BLS) in medicine students from the University of Granada. Method: This was an observational, transversal descriptive study, which established as target population students from the Faculty of Medicine (University of Granada) who attended fourth and fifth year. The Study period comprised between October 2015 and January 2017. The data which was used was obtained in an initial evaluation that was done at the Faculty of Medicine and in a re-evaluation which was applied to a selected sample of students from each year. All the students included voluntarily in the study were enrolled in the subject Internal Medicine II. The analysis was carried out using measures of central tendency, frequency tables and after that, a statistical analysis using the Student´s T-test. Results: Fourth year students obtained an average in the first evaluation of 13,91 over 15 points, while in the second evaluation it was 13,81. Meanwhile, fifth year students achieved an average of 13,80 in the first evaluation and of 13,18 in the re-evaluation. This data speak of very satisfactory results for students in both years, although the impact of the oblivion curve is higher in students who have spent more time without taking a recycling course of BLS. Conclusions:.Even though there is a decrease of knowledge and abilities related to the practice of basic life support a year after receiving the specific training in both groups, there are not differences statistically significant for the subjects of our group that would make us establish recycling programs after six or nine months, as advice the actual recommendations. 2.Based on the results we obtained, we would recommend the development of specific recycling programs in periods of time bigger than twelve months after receiving the initial training

SNP genotyping in melons: genetic variation, population structure, and linkage disequilibrium

Novel sequencing technologies were recently used to generate sequences from multiple melon (Cucumis melo L.) genotypes, enabling the in silico identification of large single nucleotide polymorphism (SNP) collections. In order to optimize the use of these markers, SNP validation and large-scale genotyping are necessary. In this paper, we present the first validated design for a genotyping array with 768 SNPs that are evenly distributed throughout the melon genome. This customized Illumina GoldenGate assay was used to genotype a collection of 74 accessions, representing most of the botanical groups of the species. Of the assayed loci, 91 % were successfully genotyped. The array provided a large number of polymorphic SNPs within and across accessions. This set of SNPs detected high levels of variation in accessions from this crop’s center of origin as well as from several other areas of melon diversification. Allele distribution throughout the genome revealed regions that distinguished between the two main groups of cultivated accessions (inodorus and cantalupensis). Population structure analysis showed a subdivision into five subpopulations, reflecting the history of the crop. A considerably low level of LD was detected, which decayed rapidly within a few kilobases. Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in melon. Since many of the genotyped accessions are currently being used as the parents of breeding populations in various programs, this set of mapped markers could be used for future mapping and breeding efforts.This project was carried out in the frame of the MELONOMICS project (2009–2012) of the Fundación Genoma España and with the contributions of the PLAT KKBE project PIM2010PKB-00691.Peer reviewe

Enhancement of vortex liquid phase and reentrant behavior in NiBi_(3) single crystals

We investigate the vortex phase diagram of needle shaped high quality NiBi3 single crystals by transport measurements. The current is applied along the crystalline b-axis of this intermetallic quasi-1D BCS superconductor. The single crystals show a Ginzburg-Levanyuk (G (i)) parameter of about 10(-7), larger by two orders of magnitude than G _(i) in elemental low T_(c) BCS superconductors. Vortex phase diagram, critical currents and pinning forces have been extracted from the experimental data. We observe (i) an enhancement of the vortex liquid phase, (ii) a reentrance of the liquid phase at low fields and (iii) an unusual magnetic field dependence of the pinning force. We suggest that these phenomena result from the interplay between pinning due to quenched disorder and the quasi-1D character of the material which could lead, for instance, to more complex pinning mechanisms at play

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

Hypersensitive response to Aphis gossypii Glover in melon genotypes carrying the Vat gene

Aphis gossypii Glover causes direct and indirect damage to Cucumis melo L. crops. To decrease the harmful effects of this pest, one of the most economically and environmentally acceptable options is to use genetically resistant melon varieties. To date, several sources of resistance carrying the Vat gene are used in melon breeding programmes that aim to prevent A. gossypii colonization and the subsequent aphid virus transmission. The results suggest that the resistance conferred by this gene is associated with a microscopic hypersensitive response specific against A. gossypii.CICYT Spanish National Research Project: AGL2005-03850-C02-01.Peer reviewe

Patrones de consumo de alcohol, tabaco y drogas ilegales en personas transexuales.

This study evaluated the patterns of substance use in a large sample of male-to-female (MtoF) and female-to-male (FtoM) transsexuals. A total of 251 transsexual subjects (163 MtoF and 88 FtoM), attended in the Catalonia Gender Unit, completed self-administrated questionnaires on consumption of alcohol, tobacco, cannabis, cocaine, opioids, and designer drugs. Results were compared with the general population in Catalonia using data from the National Health Service (EDADES 2013 study). Current consumption of alcohol (70.1%), tobacco (46.2%), and cannabis (16.3%) among transsexuals was similar when compared with men (72.1%, 42.1%, 12.8%) and increased when compared with women (57.6%, 35.2%, 5%); the consumption between MtoF and FtoM subgroups was similar.  The use of cocaine was almost ten times more prevalent in the MtoF subgroup than in the FtoM subgroup (1.1%), and in general population (less than 1%).  Only a few reported uses of opioids and designer drugs. In conclusion, the substance use among transsexuals, except for the use of cocaine, was similar between MtoF and FtoM subgroups, and resembled the consumption prevalence among men in the general population. The proportion of cocaine consumers in the MtoF subgroup was up to ten times higher than in other subgroups