Duplication and subfunctionalisation of the general transcription factor IIIA (gtf3a) gene in teleost genomes, with ovarian specific transcription of gtf3ab

Fish oogenesis is characterised by a massive growth of oocytes each reproductive season. This growth requires the stockpiling of certain molecules, such as ribosomal RNAs to assist the rapid ribosomal assembly and protein synthesis required to allow developmental processes in the newly formed embryo. Massive 5S rRNA expression in oocytes, facilitated by transcription factor 3A (Gtf3a), serves as marker of intersex condition in fish exposed to xenoestrogens. Our present work on Gtf3a gene evolution has been analysed in silico in teleost genomes and functionally in the case of the zebrafish Danio rerio. Synteny-analysis of fish genomes has allowed the identification of two gtf3a paralog genes, probably emerged from the teleost specific genome duplication event. Functional analyses demonstrated that gtf3ab has evolved as a gene specially transcribed in oocytes as observed in Danio rerio, and also in Oreochromis niloticus. Instead, gtf3aa was observed to be ubiquitously expressed. In addition, in zebrafish embryos gtf3aa transcription began with the activation of the zygotic genome (similar to 8 hpf), while gtf3ab transcription began only at the onset of oogenesis. Under exposure to 100 ng/L 17 beta-estradiol, fully feminised 61 dpf zebrafish showed transcription of ovarian gtf3ab, while masculinised (100 ng/L 17 alpha-methyltestosterone treated) zebrafish only transcribed gtf3aa. Sex related transcription of gtf3ab coincided with that of cyp19a1a being opposite to that of amh and dmrt1. Such sex dimorphic pattern of gtf3ab transcription was not observed earlier in larvae that had not yet shown any signs of gonad formation after 26 days of oestradiol exposure. Thus, gtf3ab transcription is a consequence of oocyte differentiation and not a direct result of estrogen exposure, and could constitute a useful marker of gonad feminisation and intersex condition.This work has been funded through research projects of MINECO (AGL2012-33477 and AGL2015-63936_R), Basque-Government (PhD fellowship to IRB, S-PE13UN101 & IT81013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Generation of Tertiary and Quaternary Stereocenters via Palladium-Catalyzed Intramolecular Heck-type Reactions for the Stereocontrolled Synthesis of Pyrrolo[1,2-b]isoquinolines

The generation of quaternary and tertiary stereocenters on C-10 of the pyrroloisoquinoline skeleton through intramolecular Mizoroki-Heck reactions of 2-alkenyl substituted pyrroles and pyrrolidines has been studied. The cyclizations proceeded with moderate to good yields (up to 81%), although with low enantioselection when chiral phosphanes, such as (R)-BINAP, are used as ligands. However, enantiomerically pure 10-substituted pyrrolo[1,2-b]isoquinolines have been efficiently obtained through a diastereoselective approach using chiral non-racemic pyrrolidines as substrates, generating a tertiary stereocenterMinisterio de Economía y Competitividad (CTQ2013-41229-P), Gobierno Vasco (IT-623-13), Universidad del País Vasco / Euskal Herriko Unibertsitatea UPV/EHU (UFI11/22, PPM12/03

Prediction of Antileishmanial Compounds: General Model, Preparation, and Evaluation of 2‑Acylpyrrole Derivatives

In this work, the SOFT.PTML tool has been used to pre-process a ChEMBL dataset of pre-clinical assays of antileishmanial compound candidates. A comparative study of different ML algorithms, such as logistic regression (LOGR), support vector machine (SVM), and random forests (RF), has shown that the IFPTML-LOGR model presents excellent values of specificity and sensitivity (81−98%) in training and validation series. The use of this software has been illustrated with a practical case study focused on a series of 28 derivatives of 2-acylpyrroles 5a,b, obtained through a Pd(II)-catalyzed C−H radical acylation of pyrroles. Their in vitro leishmanicidal activity against visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis was evaluated finding that compounds 5bc (IC50 = 30.87 μM, SI > 10.17) and 5bd (IC50 = 16.87 μM, SI > 10.67) were approximately 6-fold more selective than the drug of reference (miltefosine) in in vitro assays against L. amazonensis promastigotes. In addition, most of the compounds showed low cytotoxicity, CC50 > 100 μg/ mL in J774 cells. Interestingly, the IFPMTL-LOGR model predicts correctly the relative biological activity of these series of acylpyrroles. A computational high-throughput screening (cHTS) study of 2-acylpyrroles 5a,b has been performed calculating >20,700 activity scores vs a large space of 647 assays involving multiple Leishmania species, cell lines, and potential target proteins. Overall, the study demonstrates that the SOFT.PTML all-in-one strategy is useful to obtain IFPTML models in a friendly interface making the work easier and faster than before. The present work also points to 2-acylpyrroles as new lead compounds worthy of further optimization as antileishmanial hits.Ministerio de Ciencia e Innovación (PID2019-104148GB-I00), Gobierno Vasco (IT1558-22

An expert consensus report on the clinical use of the Vycross® hyaluronic acid VYC-25 L filler.

Background: The portfolio of hyaluronic acid (HA) fillers and the techniques of administration have evolved in recent years. The latest innovation in the Vycross® range was the introduction of VYC-25L (Juvéderm Volux®; Allergan plc), a first-in- class filler effective for chin and facial lower third remodeling. The aim here was to provide clinicians who are starting to use VYC-25L with key advice, and to standardize procedures so that optimal and predictable outcomes can be obtained. Methods: A multidisciplinary group of experts in esthetic medicine from Spain and Portugal reviewed the properties, treatment paradigms, administration techniques, and potential complications of VYC-25L, on the basis of which they drafted consensus recommendations for its clinical use. Results: The consensus panel provided specific recommendations focusing on the patient profile, dose, administration techniques, and the complications of VYC-25L and their management. The panel identified five different profiles of patients who may benefit from VYC-25L, and they drafted recommendations aimed to facilitate the treatment of these patients, namely, microgenia (women/men), masculinization (men), rejuvenation (women/men), facial laxity (women/men), and submental convexity (women/men). In terms of their safety, no specific recommendations were made beyond those established for other HA fillers. Conclusions: The evolution of esthetic medicine makes it necessary to update the clinical recommendations that guide patient assessment and treatment with the new HA fillers developed. The current consensus document addresses relevant issues related to the use of VYC-25L on different types of patient, in an attempt to standardize procedures and help specialists obtain predictable results.post-print806 K

Acute liver failure due to visceral leishmaniasis in Barcelona: a case report

Background: Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions. Case presentation: We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed. Conclusions: Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis

Molecular aggregation of naphthalimide organic semiconductors assisted by amphiphilic and lipophilic interactions: a joint theoretical and experimental study

Amphiphilic and lipophilic donor–acceptor naphthalimide–oligothiophene assemblies exhibiting almost identical intramolecular properties, but differing in their intermolecular interactions, have been synthesized. Here we analyze the effect of replacing the normally used lipophilic alkyl chains with hydrophilic ones in directing molecular aggregation from an antiparallel to a parallel stacking. This different molecular packing of the amphiphilic, NIP-3TAmphi, and lipophilic, NIP-3TLipo, systems is assessed by electronic spectroscopies, scanning electronic microscopy and DFT quantum-chemical calculations. Theoretical calculations indicate that the presence of amphiphilic interactions promotes a face-to-face parallel arrangement of neighbor molecules, which induces improved electronic coupling and therefore enhances the charge transport ability and photoconducting properties of this type of materials. Time of flight and photoconducting measurements are used to determine the impact of the amphiphilic and lipophilic interactions on their possible performance in optoelectronic devices.We thank the MINECO of Spain (MAT2014-52305-P and MAT2016-77608-C3-2-P) and the UCM-BSCH joint project (GR3/14-910759), for financial support at Complutense University of Madrid. Research at University of Malaga was supported by MINECO (CTQ2015-66897-P) and Junta de Andalucia (P09-4708). R. P. O. and I. A.-M. thank the MINECO of Spain for a “Ramón y Cajal” research contract and for a predoctoral fellowship, respectively. The work performed at the University of Alicante was funded by MINECO through grant no. MAT-2011-28167-C02-01

Self-concept and subjective well-being based on gender and educational level in adolescence

Resumen basado en el de la publicaciónTítulo, resumen y palabras clave en español e inglésResumen extendido en inglésSe analizan las relaciones entre el autoconcepto y el bienestar subjetivo (satisfacción con la vida, afecto positivo y afecto negativo). Participaron 1.250 estudiantes de Educación Secundaria Obligatoria seleccionados aleatoriamente. Se administraron los siguientes instrumentos de evaluación: el Cuestionario de Autoconcepto Dimensional, la Escala de Satisfacción con la Vida y la Escala de Balance Afectivo. Los resultados indican que los adolescentes con autoconcepto alto presentan puntuaciones significativamente más altas que sus iguales con autoconcepto bajo en satisfacción con la vida y afecto positivo y puntuaciones más bajas en afecto negativo. Este patrón de resultados es el mismo tanto para la muestra total como para las muestras en función del sexo y el nivel educativo.ES

School engagement and multidimensional self-concept in a sample of Spanish secondary students

Nowadays the study of school engagement is a subject of great interest in the field of education for its decisive role in the positive development and academic success of students. This study had three main aims: firstly, to explore the possible differences of educational stage in the multidimensional self-concept and school engagement among students; secondly, to analyze the relationship of multidimensional self-concept and school engagement; and thirdly, to test multidimensional self-concept as predictor of school engagement. The sample comprised 1034 participants from 11 to 17 years old (M = 13.84; SD = 1.38), of whom 537(51.9%) were women and 497(48.1 %) men. The Multidimensional Self-Concept Questionnaire (AUDIM) of Fernández-Zabala, Goñi, Rodríguez-Fernández &amp; Goñi (2015) and the School Engagement Measure (SEM) of Fredericks, Blumenfeld, Friedel &amp; Paris (2005) were administered. The results confirmed that there was a lower level in scores of multidimensional self-concept (physical, general and academic) and school engagement in the second cycle of secondary education than in the first one. There were significant correlations between the majority of dimensions of self-concept and school engagement with medium-high effect size. Academic self-concept was identified as the most important predictor variable of school engagement.</p

The role of affect-communication and rule setting in perceived family support and school adjustment

Previous research suggests that parental socialization styles affect the implementation of family support strategies and are related to school adjustment. Nevertheless, the precise nature of the influence of socialization practices on these variables during adolescence has yet to be determined. The aim of this study was therefore to examine (separately) the direct influence of maternal and paternal affectcommunication and rule setting on adolescent participants' perceived family support, and to analyze the relationship between these dimensions and school adjustment. The sample comprised 1190 secondary school and Spanish Baccalaureate students (47.1% boys and 52.3% girls; Mage = 14.76 years, SD = 1.55) from the Autonomous Community of the Basque Country. The Affect Scale (EA-H) and the Rules and Demands Scale (ENE-H) were used to assess parental socialization practices, and the subscale for perceived family support from the Social Support from Family and Friends (AFA-R) measure and the School Engagement Measure (SEM) were used to assess school engagement, with the mean grades earned by participants being taken as a measure of academic performance. The results obtained reveal that paternal affect-communication contributes more than maternal affect-communication to adolescents' perception of having family support, whereas in relation to rules, only maternal rule setting was found to have an effect on perceived family support, with this effect being negative. Both components of parenting styles were found to be linked to school engagement. In the final sections, the data are discussed and the study's limitations presented