The gene YALI0E20207g from Yarrowia lipolytica encodes an N-acetylglucosamine kinase implicated in the regulated expression of the genes from the N-acetylglucosamine assimilatory pathway

This is an open access article distributed under the terms of the Creative Commons Attribution License.The non-conventional yeast Yarrowia lipolyticapossesses an ORF, YALI0E20207g, which encodes a protein with an amino acid sequence similar to hexokinases fromdifferent organisms. We have cloned that gene and determined several enzymatic properties of its encoded protein showing that it is an N-acetylglucosamine (NAGA) kinase. This conclusion was supported by the lack of growth in NAGA of a strain carrying a YALI0E20207g deletion.We named this gene YlNAG5. Expression of YlNAG5 as well as that of the genes encoding the enzymes of the NAGA catabolic pathway - identified by a BLAST search - was induced by this sugar. Deletion of YlNAG5 rendered that expression independent of the presence of NAGA in the medium and reintroduction of the gene restored the inducibility, indicating that YlNag5 participates in the transcriptional regulation of the NAGA assimilatory pathway genes. Expression of YlNAG5 was increased during sporulation and homozygous Ylnag5/Ylnag5 diploid strains sporulated very poorly as compared with a wild type isogenic control strain pointing to a participation of the protein in the process. Overexpression of YlNAG5 allowed growth in glucose of an Ylhxk1 glk1 double mutant and produced, in a wild type background, aberrant morphologies in different media. Expression of the gene in a Saccharomyces cerevisiae hxk1 hxk2 glk1 triple mutant restored ability to grow in glucose.This work was supported by grant BFU2010-19628-C02-02 from the Spanish Ministry for Science and Innovation (MICINN, now MINECO).Peer Reviewe

Caracterización y motivaciones de un diario de viaje de la literatura virreinal: De Salamanca, España, a Ciudad Real, Chiapas (1544-1546) de fray Tomás de la Torre.

Este trabajo pretende estudiar el diario de viaje de fray Tomás de la Torre, escrito a mediados del siglo XVI y cuyo manuscrito original se ha perdido. Para ello, es preciso atender al análisis de los problemas de su historia textual y de contenido. En concreto, de las transcripciones, ya que muestran ciertas modificaciones que, aunque nos permiten su reconstrucción, implican una hibridación entre las voces del relator y del transcriptor. A su vez, también se van a examinar las distintas causas que motivaron la redacción de este texto. Por un lado, encontramos razones políticas ligadas a la apología de la implantación de las Leyes Nuevas en América y; por otro, religiosas, fuertemente marcadas por la condición de su autor, como la defensa de la evangelización en América, la exaltación de su orden religiosa o la alabanza de Dios. Finalmente, también se tendrá en cuenta el gran número de descripciones paisajísticas y antropológicas que presenta el diario de viaje, que demuestran un constante intento por parte del autor de dar a conocer un mundo totalmente desconocido para el lector.<br /

Influence of the critical parameters on the density estimate of some fatty acids by the Rackett's method

9 páginas, 3 figuras, 3 tablas.[ES] En este trabajo se realiza un estudio comparativo de las propiedades críticas temperatura y presión en los ácidos grasos palmítico, esteárico y oléico, proporcionadas por diferentes fuentes bibliográficas. Estas propiedades se utilizan en la ecuación de Rackett para estimar la densidad de las sustancias puras. Se describen y emplean los métodos más comúnmente aplicados en estos casos para estimar dichas propiedades críticas. Se selecciona un conjunto de valores de propiedades críticas para aplicarlas en la estimación de la densidad por la ecuación de Rackett. Se proponen los valores de las propiedades críticas con los que se obtiene una mejor estimación de la densidad, cuando se compara con resultados experimentales. Se demuestra que la selección de las propiedades críticas influye de forma decisiva en la estimación de propiedades físicas mediante la ecuación de Rackett.[EN] In this work a comparative study is carried out of the critical properties of temperature and pressure applied for the palmitic, stearic and oleic fatty acids, provided by different bibliographical sources. These properties are used in the Rackett's equation to estimate the density of the pure substances. The most commonly employed methods are described and applied in these cases to estimate these critical properties. A group of values of critical properties is selected to estimate the density using the Rackett's equation. The values of the critical properties that give a better estimation of the density, according to Rackett's equation, when compared with the experimental results are proposed. It is demonstrated that the selection of the critical properties influences in a decisive way in the estimation of physical properties by means of the Rackett's equation.Los autores hacen constar su agradecimiento a: La Comisión Interministerial de Ciencia y Tecnología, por la ayuda recibida para la realización de este trabajo: ALI 95 0517. Al Instituto de Cooperación Iberoamericana (ICI), por la beca proporcionada para la realización de la Tesis Doctoral.Peer reviewe

The N-acetylglucosamine kinase from Yarrowia lipolytica is a moonlighting protein

Altres ajuts: grant CIVP18A3896 from the Fundación Ramón ArecesIn Yarrowia lipolytica, expression of the genes encoding the enzymes of the N-acetylglucosamine (NAGA) utilization pathway (NAG genes) becomes independent of the presence of NAGA in a Ylnag5 mutant lacking NAGA kinase. We addressed the question of whether the altered transcription was due to a lack of kinase activity or to a moonlighting role of this protein. Glucosamine-6-phosphate deaminase (Nag1) activity was measured as a reporter of NAG genes expression. The NGT1 gene encoding the NAGA transporter was deleted, creating a Ylnag5 ngt1 strain. In glucose cultures of this strain, Nag1 activity was similar to that of the Ylnag5 strain, ruling out the possibility that NAGA derived from cell wall turnover could trigger the derepression. Heterologous NAGA kinases were expressed in a Ylnag5 strain. Among them, the protein from Arabidopsis thaliana did not restore kinase activity but lowered Nag1 activity 4-fold with respect to a control. Expression in the Ylnag5 strain of YlNag5 variants F320S or D214V with low kinase activity caused a repression similar to that of the wild-type protein. Together, these results indicate that YlNag5 behaves as a moonlighting protein. An RNA-seq analysis revealed that the Ylnag5 mutation had a limited transcriptomic effect besides derepression of the NAG genes

Treatment for acute uncomplicated diverticulitis without antibiotherapy: systematic review and meta-analysis of randomized clinical trials

Background: Use of antibiotics in selected cases of acute uncomplicated diverticulitis (AUD) has recently been questioned. Objective: The aim of this study is to examine the safety and efficacy of treatment regimens without antibiotics compared with that of traditional treatments with antibiotics in selected patients with AUD. Data sources: PubMed, Medline, Embase, Web of Science, and the Cochrane Library Methods: A systematic review was performed according to PRISMA and AMSTAR guidelines by searching through Medline, Embase, Web of Science, and the Cochrane Library for randomized clinical trials (RCTs) published before December 2022. The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. Study selection: RCTs on treating AUD without antibiotics published in English before December 2022 were included. Intervention: Treatments without antibiotics were compared with treatments with antibiotics. Main outcome measures: The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. Results: The search yielded 1163 studies. Four RCTs with 1809 patients were included in the review. Among these patients, 50.1% were treated conservatively without antibiotics. The meta-analysis showed no significant differences between nonantibiotic and antibiotic treatment groups with respect to rates of readmission [odds ratio (OR) = 1.39; 95% CI: 0.93-2.06; P = 0.11; I-2 = 0%], change in strategy (OR = 1.03; 95% CI: 0.52-2,02; P = 0.94; I-2 = 44%), emergency surgery (OR = 0.43; 95% CI: 0.12-1.53; P = 0.19; I-2 = 0%), worsening (OR = 0.91; 95% CI: 0.48-1.73; P = 0.78; I-2 = 0%), and persistent diverticulitis (OR = 1.54; 95% CI: 0.63-3.26; P = 0.26; I-2 = 0%). Limitations: Heterogeneity and a limited number of RCTs. Conclusions: Treatment for AUD without antibiotic therapy is safe and effective in selected patients. Further RTCs should confirm the present findings

Chemical constituents, anticancer and anti-proliferative potential of limonium species: a systematic review

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cell lines (especially hepatocellular carcinoma—HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.info:eu-repo/semantics/publishedVersio

Analysis of mrp4/abcc4-induced epigenetic signature in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a dismal prognosis. Histone deacetylases (HDACs) and demethylases (KDMs), as well as DNA methylases (DNMTs) and demethylases (TETs), are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, HDAC1 and HDAC2 have been shown to play an important role in the control of proliferation, apoptosis, differentiation, migration, and angiogenesis of PDAC cells. The multidrug resistance-associated protein 4 MRP4/ABCC4 is a xenobiotic transporter involved in the regulation of cAMP signaling by extrusion to the extracellular compartment. MRP4 was found highly expressed in PDAC, and its expression correlates with increased proliferation and poor prognosis. MRP4 overexpression in the PDAC cell line BxPC-3 increased proliferation, and cell inoculation in NGS mice produced xenografts with increased weight and poor differentiation compared to mock tumors. Therefore, we aimed to analyze how MRP4 overexpression collaborates in PDAC malignant epigenetic and transcriptional signature that enables tumor progression. We analyzed the expression of several epigenetic modulators in MRP4-overexpressing BxPC-3 tumors (MRP4+), compared to wild type tumors (WT) and tumors transfected with an empty vector (mock). We found increased HDAC1 and HDAC2 mRNA and protein levels, and concomitantly decreased acetylation of H3K9ac, in MRP4+ compared to WT/mock (p<0.05). MRP4+ tumors also showed increased mRNA expression of key enzymes involved in epigenetic control of cancer progression: Sirt1 and Kdm1a (LSD1), involved in histone deacetylation and demethylation, and Dnmt1 and Tet1, linked to aberrant methylation/demethylation patterns in DNA. These findings suggest that, in pancreatic cancer, MRP4 contributes to the establishment of an aberrant epigenetic signature and altered transcriptional program which may drive cells towards a proliferative and undifferentiated phenotype.Fil: Gancedo, Samanta Nerea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gonzalez, Betina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Sahores, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Gomez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Lagos, Rodrigo Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaFil: Davio, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones Farmacológicas; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de Laboratori

Compartir saberes para cuidar mejor: "aulas invertidas" y producción colaborativa de conocimiento

Depto. de Sociología: Metodología y TeoríaFac. de Ciencias Políticas y SociologíaFALSEsubmitte

Flavonoid as possible therapeutic targets against COVID-19: a scoping review of in silico studies

Objectives: This scoping review aims to present flavonoid compounds' promising effects and possible mechanisms of action on potential therapeutic targets in the SARS-CoV-2 infection process. Methods: A search of electronic databases such as PubMed and Scopus was carried out to evaluate the performance of substances from the flavonoid class at different stages of SARS-CoV-2 infection. Results: The search strategy yielded 382 articles after the exclusion of duplicates. During the screening process, 265 records were deemed as irrelevant. At the end of the full-text appraisal, 37 studies were considered eligible for data extraction and qualitative synthesis. All the studies used virtual molecular docking models to verify the affinity of compounds from the flavonoid class with crucial proteins in the replication cycle of the SARS-CoV-2 virus (Spike protein, PLpro, 3CLpro/ MPro, RdRP, and inhibition of the host's ACE II receptor). The flavonoids with more targets and lowest binding energies were: orientin, quercetin, epigallocatechin, narcissoside, silymarin, neohesperidin, delphinidin-3,5-diglucoside, and delphinidin-3-sambubioside-5-glucoside. Conclusion: These studies allow us to provide a basis for in vitro and in vivo assays to assist in developing drugs for the treatment and prevention of COVID-19.This study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científco e Tecnológico (CNPq). We would like to thank the Programa de Graduação em Ciências Farmacêuticas at Universidade Estadual do Oeste do Paraná, Universidade Estadual de Maringá, Centro Universitário Ingá, Universidade do Porto and Universidade Federal do Paraná.info:eu-repo/semantics/publishedVersio

Bioactive compounds as potential angiotensin-converting enzyme II inhibitors against COVID-19: a scoping review

Objective and design: The current study aimed to summarize the evidence of compounds contained in plant species with the ability to block the angiotensin-converting enzyme 2 (ACE-II), through a scoping review. Methods: PubMed and Scopus electronic databases were used for the systematic search and a manual search was performed RESULTS: Studies included were characterized as in silico. Among the 200 studies retrieved, 139 studies were listed after the exclusion of duplicates, and 74 were included for the full read. Among them, 32 studies were considered eligible for the qualitative synthesis. The most evaluated class of secondary metabolites was flavonoids with quercetin and curcumin as most actives substances and terpenes (isothymol, limonin, curcumenol, anabsinthin, and artemisinin). Other classes also evaluated were alkaloid, saponin, quinone, substances found in essential oils, and primary metabolites such as the aminoacid L-tyrosine and the lipidic compound 2-monolinolenin. Conclusion: This review suggests the most active substance from each class of metabolites, which presented the strongest affinity to the ACE-II receptor, which contributes as a basis for choosing compounds and directing further experimental and clinical investigation on the applications these compounds in biotechnological and health processes as in COVID-19 pandemic.info:eu-repo/semantics/publishedVersio