Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization

The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anion

Crystal structures of the HCl salts of pseudopeptidic macrocycles display ‘‘knobs into holes’’ hydrophobic interactions between aliphatic side chains

The crystal structures of three HCl salts of pseudopeptidic macrocycles show a H-bonding tubular stack of the rings, where the amino acidic side chains (Val, Leu, Ile) display an inter-columnar “knobs into holes” hydrophobic interaction patter

仏蘭西法律書目録 [書写資料] / 仏・トリピエー

刊行年不明法制-外国法 / 和装kosh

Male homophily in South American herpetology: one of the major processes underlying the gender gap in publications

The growing number of gender studies encourages more refined analyzes and greater conceptualization of the underlying processes of gender gap in science. In Herpetology, previous studies have described gender disparities and a scrutiny of individual interactions may help revealing the mechanisms modelling the global pattern. In this contribution we modeled a co-authorship network, a previously unexplored methodology for gender studies in this discipline, in addition to a broad and classic bibliometric analysis of the discipline. Co-authorship networks were modelled for two South American journals, because this geo-political location is considered to present the best gender balance within general scientific communities. However, we found a pattern of male preferential connections (male homophily) that marginalizes women and maintains the gender gap, at both regional and global scales. This interpretation arises from results coming from multiple analyses, such as high homophily index in collaboration networks, lower female representation in articles than expected in a non-gender biased environment, the decrease of female co-authors when the article leader is a man, and the extreme masculinization of the editorial boards. The homophilic dynamics of the publication process reveals that academic activity is pervasive to unbalanced power relationships. Personal interactions shape the collective experience, tracing back to the Feminist Theory´s axiom: "the personal is political".Fil: Grosso, Jimena Renee. Universidad Austral de Chile; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Humedales Río Cruces (uach); ChileFil: Fratani Da Silva, Jéssica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Correlación Geológica. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Departamento de Geología. Cátedra Geología Estructural. Instituto Superior de Correlación Geológica; ArgentinaFil: Fontanarrosa, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Bio y Geociencias del Noroeste Argentino; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto de Biodiversidad Neotropical; ArgentinaFil: Chuliver Pereyra, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Bio y Geociencias del Noroeste Argentino; ArgentinaFil: Duport Bru, Ana Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schneider, Rosio Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Casagranda, Maria Dolores. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; ArgentinaFil: Ferraro, Daiana Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Vicente, Natalin Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salica, María José. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pereyra, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; ArgentinaFil: Medina, Regina Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Tucumán; Argentina. Universidad Católica de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Bessa, Carla Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Semhan, Romina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera, Miriam Corina. Universidad Nacional de Misiones. Facultad de Humanidades y Ciencias Sociales. Departamento de Genética. Laboratorio de Genética Evolutiva y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Carta a los Editores

Las actividades profesionales son afectadas por las construcciones socioculturales que configuran los roles, las percepciones, y el estatus de las mujeres y los hombres en una sociedad. El ámbito científico no es ajeno a esta situación y las desigualdades de género en ciencia son ampliamente conocidas. Es por eso que en los últimos tiempos en la comunidad científica, en consonancia con el movimiento global por los derechos de las mujeres, se ha suscitado un proceso de autoevaluación bajo una perspectiva de género (Scott et al., 2010; Shen, 2013; Greshake Tzovaras, 2017; Berenbaum, 2019). En Argentina, pese a que las mujeres representan el 53% del conjunto de investigadores del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, 2020), su participación en cargos superiores—académicos y administrativos—es minoritaria, alcanzando por ejemplo en 2018 sólo el 23% de representación en la categoría superior de CONICET (Baringoltz y Posadas, 2009; CONICET, 2020). Este marcado sesgo de género en puestos jerárquicos es un patrón conocido como techo de cristal, que da cuenta de las limitaciones del ascenso laboral de las mujeres en una organización (Lühe, 2014).Asociación Herpetológica Argentin

Carta a los Editores

Las actividades profesionales son afectadas por las construcciones socioculturales que configuran los roles, las percepciones, y el estatus de las mujeres y los hombres en una sociedad. El ámbito científico no es ajeno a esta situación y las desigualdades de género en ciencia son ampliamente conocidas. Es por eso que en los últimos tiempos en la comunidad científica, en consonancia con el movimiento global por los derechos de las mujeres, se ha suscitado un proceso de autoevaluación bajo una perspectiva de género (Scott et al., 2010; Shen, 2013; Greshake Tzovaras, 2017; Berenbaum, 2019). En Argentina, pese a que las mujeres representan el 53% del conjunto de investigadores del Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, 2020), su participación en cargos superiores—académicos y administrativos—es minoritaria, alcanzando por ejemplo en 2018 sólo el 23% de representación en la categoría superior de CONICET (Baringoltz y Posadas, 2009; CONICET, 2020). Este marcado sesgo de género en puestos jerárquicos es un patrón conocido como techo de cristal, que da cuenta de las limitaciones del ascenso laboral de las mujeres en una organización (Lühe, 2014).Asociación Herpetológica Argentin

The SISAL database: a global resource to document oxygen and carbon isotope records from speleothems

Stable isotope records from speleothems provide information on past climate changes, most particularly information that can be used to reconstruct past changes in precipitation and atmospheric circulation. These records are increasingly being used to provide “out-of-sample” evaluations of isotope-enabled climate models. SISAL (Speleothem Isotope Synthesis and Analysis) is an international working group of the Past Global Changes (PAGES) project. The working group aims to provide a comprehensive compilation of speleothem isotope records for climate reconstruction and model evaluation. The SISAL database contains data for individual speleothems, grouped by cave system. Stable isotopes of oxygen and carbon (δ 18O, δ 13C) measurements are referenced by distance from the top or bottom of the speleothem. Additional tables provide information on dating, including information on the dates used to construct the original age model and sufficient information to assess the quality of each data set and to erect a standardized chronology across different speleothems. The metadata table provides location information, information on the full range of measurements carried out on each speleothem and information on the cave system that is relevant to the interpretation of the records, as well as citations for both publications and archived data. The compiled data are available at https://doi.org/10.17864/1947.147

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Structurally disfavoured pseudopeptidic macrocycles through anion templation

An anionic dicarboxylate is able to template the formation of geometrically disfavoured macrocycles from a dynamic covalent mixture of open chain oligoimines.Peer reviewe

Gemini amphiphilic pseudopeptides: synthesis and preliminary study of their self-assembling properties

The synthesis of a family of Gemini Amphiphilic Pseudopeptide (GAP) molecules by a reductive amination reaction has been carried out. The process is highly modular and can be efficiently performed with different pseudopeptidic diamines as well as aliphatic and aromatic aldehydes. Preliminary studies showed the abilities of the GAPs to self-assemble into supramolecular nanostructures.This work was supported by the Spanish Ministry of Science and Innovation (CTQ2009-14366-C02). J.R. thanks MICINN for personal financial support (FPU fellowship). We also thank Bogdan Duma for his helpful assistance.Peer reviewe