9 research outputs found

    Heterocycle-Based Multicomponent Reactions in Drug Discovery: From Hit Finding to Rational Design

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    In the context of the structural complexity necessary for a molecule to selectively display a therapeutical action and the requirements for suitable pharmacokinetics, a robust synthetic approach is essential. Typically, thousands of relatively similar compounds should be prepared along the drug discovery process. In this respect, heterocycle‐based multicomponent reactions offer advantages over traditional stepwise sequences in terms of synthetic economy, as well as the fast access to chemsets to study the structure activity relationships, the fine tuning of properties, and the preparation of larger amounts for preclinical phases. In this account, we briefly summarize the scientific methodology backing the research line followed by the group. We comment on the main results, clustered according to the targets and, finally, in the conclusion section, we offer a general appraisal of the situation and some perspectives regarding future directions in academic and private research

    Community-acquired pneumonia in hospitalised patients: changes in aetiology, clinical presentation, and severity outcomes in a 10-year period

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    Staphylococcus aureus; Mortality; VirologyStaphylococcus aureus; Mortalidad; VirologíaStaphylococcus aureus; Mortalitat; VirologiaBackground and objective Community-acquired pneumonia (CAP) is a frequent cause of hospitalisation. Several factors, such as pandemics, vaccines and globalisation may lead to changes in epidemiology, clinical presentation, and outcomes of CAP, which oblige to a constant actualisation. We performed this study to analyse how these factors have evolved over a 10-year period. Materials and methods Patients diagnosed with CAP for two 1-year periods that were 10 years apart (2007–2008 and 2017–2018) were included. We compared microbiological information, clinical data and evolutive outcomes in the two periods. A mortality analysis was performed. Results 1043 patients were included: 452 during the first period (2007- 2008), and 591 during the second period (2017–2018). Bacterial aetiology did not change during the 10-year period, besides a slight increase in Staphylococcus aureus (0.9% vs 2.9%, p = 0.026). There was a decline in the proportion of bacteraemia in the second period (14.8% vs 9.6%, p = 0.012). The incidence of complicated pleural effusion and septic shock declined too (6.4% vs 3.6%, p = 0.04 and 15.5% vs 6.3%, p < 0.001). Respiratory failure and Intensive care unit (ICU) admission were similar in both periods. Variables independently associated with mortality were age and septic shock. Influenza vaccine was a protective factor against mortality in the second period. Conclusions We have not found relevant differences in the bacterial aetiology of CAP over this 10-year period. There has been a decline in septic complications of CAP such as septic shock, bacteraemia, and complicated pleural effusion. Influenza vaccination is an important tool to reduce mortality

    Famílies botàniques de plantes medicinals

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    Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

    The Prohibitin-Binding Compound Fluorizoline Activates the Integrated Stress Response through the eIF2α Kinase HRI

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    Fluorizoline is a synthetic molecule that induces apoptosis, by selectively targeting prohibitins (PHBs), through induction of the BH3-only protein NOXA. This induction is transcriptionally regulated by the integrated stress response (ISR)-related transcription factors ATF3 and ATF4. Here, we evaluate the role of the four eIF2α kinases, to decipher which is responsible for the mechanism of ISR activation triggered by fluorizoline in HeLa and HAP1 cells. First, we demonstrated the involvement of the eIF2α kinases using ISR inhibitor (ISRIB) and by simultaneous downregulation of all four eIF2α kinases, as both approaches were able to increase cell resistance to fluorizoline-induced apoptosis. Furthermore, we confirmed that fluorizoline treatment results in endoplasmic reticulum (ER) stress, as evidenced by PERK activation. Despite PERK activation, this kinase was not directly involved in the ISR activation by fluorizoline. In this regard, we found that the eIF2α kinases are capable of compensating for each other’s loss of function. Importantly, we demonstrated that the mitochondrial-stress-related eIF2α kinase HRI mediates ISR activation after fluorizoline treatment

    Mobilitat activa en entorns metropolitans. Anàlisi i planejament per a la política integral de la bicicleta a la ròtula de Montcada

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    Projecte troncal del curs 2022/23 del Màster oficial en Estudis Territorials i Planejament, METiPEl document s'estructura en quatre capítols més un apèndix. El primer capítol comprèn la Memòria on s'hi pot trobar el Reconeixement Territorial i socioeconòmic i la Diagnosi de les dimensions de la política ciclista. El segon capítol comprèn les Debilitats, Fortaleses, Amenaces i Oportunitats de cada dimensió de la política integral de la bicicleta en l'àmbit d'estudi. El tercer capítol es dedica a l'establiment dels Criteris que hauran de guiar les polítiques de bicicleta. En el quart i darrer capítol es presenten les Propostes i Projectes de cada dimensió; en total es presenten 16 Propostes i 32 Projectes per al territori de la Ròtula de Montcada i Reixac. Finalment a l'apèndix hi trobareu el quadernet de treball de camp amb la planificació detallada de l'exercici troncal i els pòsters amb el recull dels principals resultats de l'exercici

    The mRNA Export Factor Sus1 Is Involved in Spt/Ada/Gcn5 Acetyltransferase-mediated H2B Deubiquitinylation through Its Interaction with Ubp8 and Sgf11

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    Sus1 acts in nuclear mRNA export via its association with the nuclear pore-associated Sac3–Thp1–Cdc31 complex. In addition, Sus1 plays a role in transcription through its interaction with the Spt/Ada/Gcn5 acetyltransferase (SAGA) complex. Here, we have analyzed function and interaction of Sus1 within the SAGA complex. We demonstrate that Sus1 is involved in the SAGA-dependent histone H2B deubiquitinylation and maintenance of normal H3 methylation levels. By deletion analyses, we show that binding of Sus1 to SAGA depends on the deubiquitinylating enzyme Ubp8 and Sgf11. Moreover, a stable subcomplex between Sus1, Sgf11, and Ubp8 could be dissociated from SAGA under high salt conditions. In vivo recruitment of Sus1 to the activated GAL1 promoter depends on Ubp8 and vice versa. In addition, histones coenrich during SAGA purification in a Sus1–Sgf11–Ubp8-dependent way. Interestingly, sgf11 deletion enhances the mRNA export defect observed in sus1Δ cells. Thus, the Sus1–Sgf11–Ubp8 module could work at the junction between SAGA-dependent transcription and nuclear mRNA export

    La conquête de la montagne : des premières occupations humaines à l’anthropisation du milieu

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