GABANELLIA AGILIS GEN. N. SP. N., (ACTINOPTERYGII, PERLEIDIFORMES) FROM THE CALCARE DI ZORZINO OF LOMBARDY (NORTH ITALY)

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REDESCRIPTION OF ‘PERLEIDUS’ (OSTEICHTHYES, ACTINOPTERYGII) FROM THE EARLY TRIASSIC OF NORTHWESTERN MADAGASCAR

The revision of the material from the Lower Triassic fossil-bearing-nodule levels from northwestern Madagascar supports the assumption that the genus Perleidus De Alessandri, 1910 is not present in the Early Triassic. In the past, the presence of this genus has been reported in the Early Triassic of Angola, Canada, China, Greenland, Madagascar and Spitsbergen. More recently, it has been pointed out that these taxa may not be ascribed to Perleidus owing to several anatomical differences. The morphometric, meristic and morphological analyses revealed a remarkable ontogenetic and individual intraspecific variation among dozens of specimens from the lower Triassic of Ankitokazo basin, northwestern Madagascar and allowed to consider the two Malagasyan species P. madagascariensis Piveteau, 1934, and P. piveteaui Lehman, 1952, as a single one and to ascribe it to the new genus Teffichthys. This new genus exhibits a unique combination of features, mainly in the skull dermal bone pattern and structure of caudal fin, that clearly support its exclusion from Perleidiformes. We also suggest to extend the use of Teffichthys for the other Early Triassic ‘Perleidus’ species except those from southern China

High-throughput docking for the identification of new influenza A virus polymerase inhibitors targeting the PA-PB1 protein-protein interaction

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Computational studies of the interaction between the HIV-1 integrase tetramer and the cofactor LEDGF/p75: Insights from molecular dynamics simulations and the informational spectrum method

A crystal structure of the integrase binding domain (IBD) of the lens epithelium-derived growth factor (LEDGF/p75) in complex with the dimer of the HIV-1 integrase (IN) catalytic core domain (CCD) provides useful information that might help in the understanding of essential protein-protein contacts in HIV-1. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. On the other hand, the biochemical characterization of the interaction between full-length IN and LEDGF/p75 has recently proved that LEDGF/p75 promotes IN tetramerization with two LEDGF/p75 IBD molecules bound to the IN tetramer. This experimental evidence suggests that to obtain a complete structural description of the interactions between the two proteins, the full-length tetrameric structure of IN should be considered. Our aim was to obtain a detailed picture of HIV-1 IN interactions with cellular co-factors that was of general interest, particularly for the development of small molecule IN inhibitors, which mimic the IBD of LEDGF/p75. To this end, we performed bioinformatics analyses to identify protein sequence domains involved in long-range recognition. Subsequently, we applied molecular dynamics techniques to investigate the detailed interactions between the complete tetrameric form of IN and two molecules of the IBD of LEDGF/p75. Our dynamic picture is in agreement with experimental data and, thereby, provides new details of the IN-LEDGF/p75 interaction

Attention and memory of medical residents after a night on call: a cross-sectional study

Irmandade da Santa Casa de Misericórdia de São Paulo Hospital Central Emergency RoomSanta Casa de Misericórdia de São Paulo School of Medical Science Department of Psychiatry and Medical PsychologyUniversidade Federal de São Paulo (UNIFESP) Department of Psychiatry Interdisciplinary Clinical Neurosciences LaboratoryUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasISCMSPUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de São Paulo (UNIFESP) Department of PsychiatryUNIFESP, Department of Psychiatry Interdisciplinary Clinical Neurosciences LaboratoryUNIFESP, Department of PsychiatrySciEL

Probing the Binding Site of Abl Tyrosine Kinase Using in Situ Click Chemistry

Modern combinatorial chemistry is used to discover compounds with desired function by an alternative strategy, in which the biological target is directly involved in the choice of ligands assembled from a pool of smaller fragments. Herein, we present the first experimental result where the use of in situ click chemistry has been successfully applied to probe the ligand-binding site of Abl and the ability of this enzyme to form its inhibitor. Docking studies show that Abl is able to allow the in situ click chemistry between specific azide and alkyne fragments by binding to Abl-active sites. This report allows medicinal chemists to use protein-directed in situ click chemistry for exploring the conformational space of a ligand-binding pocket and the ability of the protein to guide its inhibitor. This approach can be a novel, valuable tool to guide drug design synthesis in the field of tyrosine kinases

International Migration Drivers

The International Migration Drivers report quantifies the relative weight of the drivers of migration at international level in a comprehensive way by income levels of countries of origin. Different channels of migration (voluntary migration flows between 1980 and 2017, asylum seekers, residence permits) are analysed separately. The drivers consider both structural characteristics of countries and individual characteristics of persons planning and preparing to migrate. The study of the drivers of past migrations is used to formulate better informed migration scenarios for the future with a medium to long term perspective. In addition, findings of the report are key to understanding the root causes of migration addressed by the European Agenda on Migration and the upcoming Global Compact for Migration.JRC.E.6-Demography, Migration and Governanc

Human DDX3 protein is a valuable target to develop broad spectrum antiviral agents

Targeting a host factor essential for the replication of different viruses but not for the cells offers a higher genetic barrier to the development of resistance, may simplify therapy regimens for coinfections, and facilitates management of emerging viral diseases. DEADbox polypeptide 3 (DDX3) is a human host factor required for the replication of several DNA and RNA viruses, including some of the most challenging human pathogens currently circulating, such as HIV-1, Hepatitis C virus, Dengue virus, and West Nile virus. Herein, we showed for the first time, to our knowledge, that the inhibition of DDX3 by a small molecule could be successfully exploited for the development of a broad spectrum antiviral agent. In addition to the multiple antiviral activities, hit compound 16d retained full activity against drug-resistant HIV-1 strains in the absence of cellular toxicity. Pharmacokinetics and toxicity studies in rats confirmed a good safety profile and bioavailability of 16d. Thus, DDX3 is here validated as a valuable therapeutic target

Development and in Vitro Evaluation of a Microbicide Gel Formulation for a Novel Non-Nucleoside Reverse Transcriptase Inhibitor Belonging to the N-Dihydroalkyloxybenzyloxopyrimidines (N-DABOs) Family

17openPreventing HIV transmission by the use of a vaginal microbicide is a topic of considerable interest in the fight against AIDS. Both a potent anti-HIV agent and an efficient formulation are required to develop a successful microbicide. In this regard, molecules able to inhibit the HIV replication before the integration of the viral DNA into the genetic material of the host cells, such as entry inhibitors or reverse transcriptase inhibitors (RTIs), are ideal candidates for prevention purpose. Among RTIs, S- and N-dihydroalkyloxybenzyloxopyrimidines (S-DABOs and N-DABOs) are interesting compounds active at nanomolar concentration against wild type of RT and with a very interesting activity against RT mutations. Herein, novel N-DABOs were synthesized and tested as anti-HIV agents. Furthermore, their mode of binding was studied by molecular modeling. At the same time, a vaginal microbicide gel formulation was developed and tested for one of the most promising candidates.openTintori, Cristina; Brai, Annalaura; DASSO LANG, MARIA CHIARA; Deodato, Davide; Greco, Antonia Michela; Bizzarri, Bruno Mattia; Cascone, Lorena; Casian, Alexandru; Zamperini, Claudio; Dreassi, Elena; Crespan, Emmanuele; Maga, Giovanni; Vanham, Guido; Ceresola, Elisa; Canducci, Filippo; Ariën, Kevin K.; Botta, MaurizioTintori, Cristina; Brai, Annalaura; DASSO LANG, MARIA CHIARA; Deodato, Davide; Greco, Antonia Michela; Bizzarri, Bruno Mattia; Cascone, Lorena; Casian, Alexandru; Zamperini, Claudio; Dreassi, Elena; Crespan, Emmanuele; Maga, Giovanni; Vanham, Guido; Ceresola, Elisa; Canducci, Filippo; Ariën, Kevin K.; Botta, Maurizi