Analysis by RNA-seq of transcriptomic changes elicited by heat shock in Leishmania major

Besides their medical relevance, Leishmania is an adequate model for studying post-transcriptional mechanisms of gene expression. In this microorganism, mRNA degradation/stabilization mechanisms together with translational control and post-translational modifications of proteins are the major drivers of gene expression. Leishmania parasites develop as promastigotes in sandflies and as amastigotes in mammalians, and during host transmission, the parasite experiences a sudden temperature increase. Here, changes in the transcriptome of Leishmania major promastigotes after a moderate heat shock were analysed by RNA-seq. Several of the up-regulated transcripts code for heat shock proteins, other for proteins previously reported to be amastigote-specific and many for hypothetical proteins. Many of the transcripts experiencing a decrease in their steady-state levels code for transporters, proteins involved in RNA metabolism or translational factors. In addition, putative long noncoding RNAs were identified among the differentially expressed transcripts. Finally, temperature-dependent changes in the selection of the spliced leader addition sites were inferred from the RNA-seq data, and particular cases were further validated by RT-PCR and Northern blotting. This study provides new insights into the post-transcriptional mechanisms by which Leishmania modulate gene expressionThis work was supported by grants (to B.A. and J.M.R.) from Ministerio de Economía, Industria y Competitividad, project number SAF2017-86965-R (co-funded with FEDER funds), and by the Network of Tropical Diseases Research RICET (RD16/0027/0008), co-funded with FEDER funds. The CBMSO receives institutional grants from the Fundación Ramón Areces and from the Fundación Banco de Santande

Expert system for the assessment of power transformer insulation condition based on type-2 fuzzy logic systems

An efficient expert system for the power transformer condition assessment is presented in this paper. Through the application of Duval's triangle and the method of the gas ratios a first assessment of the transformer condition is obtained in the form of a dissolved gas analysis (DGA) diagnosis according IEC 60599. As a second step, a knowledge mining procedure is performed, by conducting surveys whose results are fed into a first Type-2 Fuzzy Logic System (T2-FLS), in order to initially evaluate the condition of the equipment taking only the results of dissolved gas analysis into account. The output of this first T2-FLS is used as the input of a second T2-FLS, which additionally weighs up the condition of the paper-oil system. The output of this last T2-FLS is given in terms of words easily understandable by the maintenance personnel. The proposed assessing methodology has been validated for several cases of transformers in service. © 2011 Elsevier Ltd. All rights reserved.Fil: Flores, Wilfredo C.. Universidad Nacional Autónoma de Honduras; Honduras. Universidad Nacional de San Juan; ArgentinaFil: Mombello, Enrique Esteban. Universidad Nacional de San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Jardini, José. A.. Universidade de Sao Paulo; BrasilFil: Rattá Gutiérrez, Giuseppe Aníbal. Universidad Nacional de San Juan; ArgentinaFil: Corvo, Antonio M.. Companhia de Transmissão de Energía Elétrica Paulista; Brasi

Sulfonic Acid-Functionalized (Bio)Materials as Catalysts for Efficient Amide Bond Synthesis

Funding Information: The authors thank Fundação para a Ciência e Tecnologia (FC&T) for project PTDC/BII‐BIO/30884/2017 and EXPL/BII‐BIO/0436/2021 and also for the researcher contract 2021.03255.CEECIND (M.C.C) and 2020.01614.CEECIND/CP1596/CT0007 (A.F.P.). Authors also thank the support by the Associate Laboratory for Green Chemistry – LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) and i3 N (LA/P/0037/2020, UIDP/50025/2020 and UIDB/50025/2020 . The National NMR Facility is supported by FC&T (ROTEIRO/0031/2013 – PINFRA/22161/2016, co‐financed by FEDER through COMPETE 2020, POCI, and PORL and FC&T through PIDDAC) and CERMAX through project 022162. We thank Prof. Dr. Carlos A. M. Afonso from the Faculty of Pharmacy, ULisboa for the scientific discussions on the experiments carried out with furfuryl alcohol derivatives. Publisher Copyright: © 2023 The Authors. ChemCatChem published by Wiley-VCH GmbH.Sulfonic acid carbon-(bio)based and natural clays-based catalysts were prepared and investigated for the first time as heterogeneous catalysts for amide bond synthesis by a Ritter reaction. The different SO3H-catalysts were screened using benzyl alcohol and acetonitrile as model substrates, and MWCNT-CSP revealed to be an efficient catalyst, affording the amide in 75 % yield. The practical utility of the catalysts was demonstrated by a diverse range of amides, obtained from alcohols and nitriles, in moderate to good yields. Biomass derived platform alcohols, such as 5-HMF and furfuryl alcohol, were also tested as potential building blocks for the synthesis of biopolymers. The SO3H-catalysts revealed to be a highly efficient and environmentally friendly alternative to the conventional acid catalysts commonly used in the Ritter reaction.publishersversionpublishe

Molecular Interactions in Ionic Liquids: The NMR Contribution towards Tailored Solvents

Ionic liquids have been on the spotlight of chemical research field in the last decades. Their physical properties (low vapor pressure, thermal stability, and conductivity) and the possibility of fine tuning make them a versatile class of compounds for a wide range of applications, such as catalysis, energy, and material sciences. Ionic liquids can establish multiple intermolecular interactions with solutes such as electrostatic, van der Waals, or hydrogen bonds. The prospect of designing ionic liquid structures toward specific applications has attracted the attention to these alternative solvents. However, their rational design demands a molecular detailed view, and Nuclear Magnetic Resonance is a unique and privileged technique for this purpose, as it provides atomic resolution and at the same time enables the study of dynamic information. In this chapter, we provide an overview about the application of Nuclear Magnetic Resonance spectroscopy techniques as a methodology for the rational design of ionic liquids as solvents for small organic compounds, CO2 capture, and polymers such as cellulose focusing mainly in the last 10 years

Synthesis and characterization of Locust Bean Gum derivatives and their application in the production of nanoparticles

The development of LBG-based nanoparticles intending an application in oral immunization is presented. Nanoparticle production occurred by mild polyelectrolyte complexation, requiring the chemical modification of LBG. Three LBG derivatives were synthesized, namely a positively charged ammonium derivative (LBGA) and negatively charged sulfate (LBGS) and carboxylate (LBGC) derivatives. These were characterized by Fourier-transform infrared spectroscopy, elemental analysis, nuclear magnetic resonance spectroscopy, gel permeation chromatography, and x-ray diffraction. As a pharmaceutical application was aimed, a toxicological analysis of the derivatives was performed by both MTT test and LDH release assay. Several nanoparticle formulations were produced using LBGA or chitosan (CS) as positively charged polymers, and LBGC or LBGS as negatively charged counterparts, producing nanoparticles with adequate properties regarding an application in oral immunization.info:eu-repo/semantics/publishedVersio

Asymmetric synthesis of N-aryl aziridines

The reactions of a variety of N-arylhydroxamates as nitrogen transfer reagents to acryloyl derivatives of (−)-8-phenylmenthol, (−)-quinine and (−)-Oppolzer’s sultam acting as Michael acceptors was studied. Poor to modest diastereoselection was observed in the formation of aziridines. The absolute structure of one of the pure diastereomers secured from Oppolzer’s auxiliary was established by X-ray crystallography and hence the absolute configuration of the derived methyl-N-phenylaziridine-2-carboxylate could be assigned. Whilst only poor facial selectivity was observed for chiral hydroxamic acid prepared from dehydroabietic acid, moderate to good enantioselection of aziridines could be achieved with the chiral quaternary salts based on cinchona alkaloids, especially with that of cinchonine. A model is presented to explain the origin of enantioselection and a mechanism is proposed for the aziridination reaction

Evidence of Strong Guest–Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41

Funding Information: This research was funded by the Associate Laboratory for Green Chemistry LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2019) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER—007265). This research was funded by the Interreg 2 Seas program 2014–2020, and co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01-059_IMODE and 2S07-033_ Site Drug. This research was funded by the Program PHC PESSOA 2018 project nbr 4340/40868R. This research was funded by National Funds through FCT—Portuguese Foundation for Science and Technology, reference UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UIDB/50025/2020-2023, and PTNMR (ROTEIRO/0031/2013; PINFRA/22161/2016), co-financed by ERDF through COMPETE 2020, Portugal, POCI and PORL and FCT through PIDDAC (POCI-01-0145-FEDER-007688). M.C.C. acknowledges PTNMR&i3N for the researcher contract. T. Cordeiro acknowledges Fundação para a Ciência e a Tecnologia (FCT) for the scholarship SFRH/BD/114653/2016. I. Matos acknowledges FCT for the Investigator FCT contract IF/01242/2014/CP1224/CT0008. Publisher Copyright: © 2023 by the authors.A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.publishersversionpublishe

Distributed Computing Grid Experiences in CMS

The CMS experiment is currently developing a computing system capable of serving, processing and archiving the large number of events that will be generated when the CMS detector starts taking data. During 2004 CMS undertook a large scale data challenge to demonstrate the ability of the CMS computing system to cope with a sustained data-taking rate equivalent to 25% of startup rate. Its goals were: to run CMS event reconstruction at CERN for a sustained period at 25 Hz input rate; to distribute the data to several regional centers; and enable data access at those centers for analysis. Grid middleware was utilized to help complete all aspects of the challenge. To continue to provide scalable access from anywhere in the world to the data, CMS is developing a layer of software that uses Grid tools to gain access to data and resources, and that aims to provide physicists with a user friendly interface for submitting their analysis jobs. This paper describes the data challenge experience with Grid infrastructure and the current development of the CMS analysis system

Quercetin Liposomal Nanoformulation for Ischemia and Reperfusion Injury Treatment

PD/BD/135264/2017 UID/DTP/04138/2020 UIDP/04138/2020 UIDP/04378/2020 UIDB/04378/2020 LA/P/0140/2020 UIDB/50006/2020 UIDB/00100/2020Ischemia and reperfusion injury (IRI) is a common complication caused by inflammation and oxidative stress resulting from liver surgery. Current therapeutic strategies do not present the desirable efficacy, and severe side effects can occur. To overcome these drawbacks, new therapeutic alternatives are necessary. Drug delivery nanosystems have been explored due to their capacity to improve the therapeutic index of conventional drugs. Within nanocarriers, liposomes are one of the most successful, with several formulations currently in the market. As improved therapeutic outcomes have been demonstrated by using liposomes as drug carriers, this nanosystem was used to deliver quercetin, a flavonoid with anti-inflammatory and antioxidant properties, in hepatic IRI treatment. In the present work, a stable quercetin liposomal formulation was developed and characterized. Additionally, an in vitro model of ischemia and reperfusion was developed with a hypoxia chamber, where the anti-inflammatory potential of liposomal quercetin was evaluated, revealing the downregulation of pro-inflammatory markers. The anti-inflammatory effect of quercetin liposomes was also assessed in vivo in a rat model of hepatic IRI, in which a decrease in inflammation markers and enhanced recovery were observed. These results demonstrate that quercetin liposomes may provide a significant tool for addressing the current bottlenecks in hepatic IRI treatment.publishersversionpublishe