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1.
Euro Surveill ; 26(46)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34794534

RESUMO

We present a European Union/European Economic Area-wide overview of the changes in consumption of antibacterials for systemic use (ATC J01) in the community between 2019 and 2020 as reported to the European Surveillance of Antimicrobial Consumption Network. Overall antibiotic consumption decreased by 18.3% between 2019 and 2020, the largest annual decrease in the network's two-decade history. We observed a strong association between the level of community antibiotic consumption in 2019 and the size of the decrease between 2019 and 2020.


Assuntos
Antibacterianos , COVID-19 , Antibacterianos/uso terapêutico , Uso de Medicamentos , Europa (Continente)/epidemiologia , União Europeia , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
2.
Plants (Basel) ; 10(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34834696

RESUMO

In the current context of climate change, plants need to develop different mechanisms of stress tolerance and adaptation to cope with changing environmental conditions. Temperature is one of the most important abiotic stresses that forest trees have to overcome. Recent research developed in our laboratory demonstrated that high temperatures during different stages of conifer somatic embryogenesis (SE) modify subsequent phases of the process and the behavior of the resulting ex vitro somatic plants. For this reason, Aleppo pine SE was induced under different heat stress treatments (40 °C for 4 h, 50 °C for 30 min, and 60 °C for 5 min) in order to analyze its effect on the global DNA methylation rates and the differential expression of four stress-related genes at different stages of the SE process. Results showed that a slight decrease of DNA methylation at proliferating embryonal masses (EMs) can correlate with the final efficiency of the process. Additionally, different expression patterns for stress-related genes were found in EMs and needles from the in vitro somatic plants obtained; the DEHYDRATION INDUCED PROTEIN 19 gene was up-regulated in response to heat at proliferating EMs, whereas HSP20 FAMILY PROTEIN and SUPEROXIDE DISMUTASE [Cu-Zn] were down-regulated in needles.

3.
Proc Natl Acad Sci U S A ; 118(41)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607952

RESUMO

Humans have made such dramatic and permanent changes to Earth's landscapes that much of it is now substantially and irreversibly altered from its preanthropogenic state. Remote islands, until recently isolated from humans, offer insights into how these landscapes evolved in response to human-induced perturbations. However, little is known about when and how remote systems were colonized because archaeological data and historical records are scarce and incomplete. Here, we use a multiproxy approach to reconstruct the initial colonization and subsequent environmental impacts on the Azores Archipelago. Our reconstructions provide unambiguous evidence for widespread human disturbance of this archipelago starting between 700-60 +50 and 850-60 +60 Common Era (CE), ca. 700 y earlier than historical records suggest the onset of Portuguese settlement of the islands. Settlement proceeded in three phases, during which human pressure on the terrestrial and aquatic ecosystems grew steadily (i.e., through livestock introductions, logging, and fire), resulting in irreversible changes. Our climate models suggest that the initial colonization at the end of the early Middle Ages (500 to 900 CE) occurred in conjunction with anomalous northeasterly winds and warmer Northern Hemisphere temperatures. These climate conditions likely inhibited exploration from southern Europe and facilitated human settlers from the northeast Atlantic. These results are consistent with recent archaeological and genetic data suggesting that the Norse were most likely the earliest settlers on the islands.

4.
Int J Biol Macromol ; 186: 54-70, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34237360

RESUMO

Lactoferrin (Lf), a bioactive milk protein, exhibits strong anticancer and antifungal activities. The search for Lf targets and mechanisms of action is of utmost importance to enhance its effective applications. A common feature among Lf-treated cancer and fungal cells is the inhibition of a proton pump called V-ATPase. Lf-driven V-ATPase inhibition leads to cytosolic acidification, ultimately causing cell death of cancer and fungal cells. Given that a detailed elucidation of how Lf and V-ATPase interact is still missing, herein we aimed to fill this gap by employing a five-stage computational approach. Molecular dynamics simulations of both proteins were performed to obtain a robust sampling of their conformational landscape, followed by clustering, which allowed retrieving representative structures, to then perform protein-protein docking. Subsequently, molecular dynamics simulations of the docked complexes and free binding energy calculations were carried out to evaluate the dynamic binding process and build a final ranking based on the binding affinities. Detailed atomist analysis of the top ranked complexes clearly indicates that Lf binds to the V1 cytosolic domain of V-ATPase. Particularly, our data suggest that Lf binds to the interfaces between A/B subunits, where the ATP hydrolysis occurs, thus inhibiting this process. The free energy decomposition analysis further identified key binding residues that will certainly aid in the rational design of follow-up experimental studies, hence bridging computational and experimental biochemistry.

5.
Front Cell Dev Biol ; 9: 642375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249904

RESUMO

Acetic acid has long been considered a molecule of great interest in the yeast research field. It is mostly recognized as a by-product of alcoholic fermentation or as a product of the metabolism of acetic and lactic acid bacteria, as well as of lignocellulosic biomass pretreatment. High acetic acid levels are commonly associated with arrested fermentations or with utilization as vinegar in the food industry. Due to its obvious interest to industrial processes, research on the mechanisms underlying the impact of acetic acid in yeast cells has been increasing. In the past twenty years, a plethora of studies have addressed the intricate cascade of molecular events involved in cell death induced by acetic acid, which is now considered a model in the yeast regulated cell death field. As such, understanding how acetic acid modulates cellular functions brought about important knowledge on modulable targets not only in biotechnology but also in biomedicine. Here, we performed a comprehensive literature review to compile information from published studies performed with lethal concentrations of acetic acid, which shed light on regulated cell death mechanisms. We present an historical retrospective of research on this topic, first providing an overview of the cell death process induced by acetic acid, including functional and structural alterations, followed by an in-depth description of its pharmacological and genetic regulation. As the mechanistic understanding of regulated cell death is crucial both to design improved biomedical strategies and to develop more robust and resilient yeast strains for industrial applications, acetic acid-induced cell death remains a fruitful and open field of study.

6.
Commun Biol ; 4(1): 521, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33953333

RESUMO

Many bacterial species and antibiotic classes exhibit heteroresistance, a phenomenon in which a susceptible bacterial isolate harbors a resistant subpopulation that can grow in the presence of an antibiotic and cause treatment failure. The resistant phenotype is often unstable and without antibiotic selection it reverts back to susceptibility. Here we studied the dynamics by which these resistant subpopulations are enriched in the presence of antibiotic and recede back to their baseline frequency in the absence of selection. An increasing understanding of this instability will allow more effective diagnostics and treatment of infections caused by heteroresistant bacteria. We show for clinical isolates of Escherichia coli and Salmonella enterica that different antibiotics at levels below the MIC of the susceptible main population can cause rapid enrichment of resistant subpopulations with increased copy number of genes that cause resistance. Modelling and growth rate measurements of bacteria with increased gene copy number in cultures and by microscopy of single-cells in a microfluidic chip show that the fitness cost of gene amplifications and their intrinsic instability drives their rapid loss in the absence of selection. Using a common antibiotic susceptibility test, we demonstrate that this test strongly underestimates the occurrence of heteroresistance in clinical isolates.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/diagnóstico , Escherichia coli/crescimento & desenvolvimento , Infecções por Salmonella/diagnóstico , Salmonella enterica/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Regulação Bacteriana da Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Infecções por Salmonella/genética , Infecções por Salmonella/microbiologia , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação
7.
Front Plant Sci ; 12: 631239, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912202

RESUMO

Somatic embryogenesis is the process by which bipolar structures with no vascular connection with the surrounding tissue are formed from a single or a group of vegetative cells, and in conifers it can be divided into five different steps: initiation, proliferation, maturation, germination and acclimatization. Somatic embryogenesis has long been used as a model to study the mechanisms regulating stress response in plants, and recent research carried out in our laboratory has demonstrated that high temperatures during initial stages of conifer somatic embryogenesis modify subsequent phases of the process, as well as the behavior of the resulting plants ex vitro. The development of high-throughput techniques has facilitated the study of the molecular response of plants to numerous stress factors. Proteomics offers a reliable image of the cell status and is known to be extremely susceptible to environmental changes. In this study, the proteome of radiata pine somatic embryos was analyzed by LC-MS after the application of high temperatures during initiation of embryonal masses [(23°C, control; 40°C (4 h); 60°C (5 min)]. At the same time, the content of specific soluble sugars and sugar alcohols was analyzed by HPLC. Results confirmed a significant decrease in the initiation rate of embryonal masses under 40°C treatments (from 44 to 30.5%) and an increasing tendency in the production of somatic embryos (from 121.87 to 170.83 somatic embryos per gram of embryogenic tissue). Besides, heat provoked a long-term readjustment of the protein synthesis machinery: a great number of structural constituents of ribosomes were increased under high temperatures, together with the down-regulation of the enzyme methionine-tRNA ligase. Heat led to higher contents of heat shock proteins and chaperones, transmembrane transport proteins, proteins related with post-transcriptional regulation (ARGONAUTE 1D) and enzymes involved in the synthesis of fatty acids, specific compatible sugars (myo-inositol) and cell-wall carbohydrates. On the other hand, the protein adenosylhomocysteinase and enzymes linked with the glycolytic pathway, nitrogen assimilation and oxidative stress response were found at lower levels.

8.
Int J Biol Macromol ; 171: 343-357, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33421469

RESUMO

Lactoferrin (Lf) is a bioactive milk-derived protein with remarkable wide-spectrum antifungal activity. To deepen our understanding of the molecular mechanisms underlying Lf cytotoxicity, the role of plasma membrane ergosterol- and sphingolipid-rich lipid rafts and their association with the proton pump Pma1p was explored. Pma1p was previously identified as a Lf-binding protein. Results showed that bovine Lf (bLf) perturbs ergosterol-rich lipid rafts organization by inducing intracellular accumulation of ergosterol. Using yeast mutant strains lacking lipid rafts-associated proteins or enzymes involved in the synthesis of ergosterol and sphingolipids, we found that perturbations in the composition of these membrane domains increase resistance to bLf-induced yeast cell death. Also, when Pma1p-lipid rafts association is compromised in the Pma1-10 mutant and in the absence of the Pma1p-binding protein Ast1p, the bLf killing activity is impaired. Altogether, results showed that the perturbation of lipid rafts and the inhibition of both Pma1p and V-ATPase activities mediate the antifungal activity of bLf. Since it is suggested that the combination of conventional antifungals with lipid rafts-disrupting compounds is a powerful antifungal approach, our data will help to pave the way for the use of bLf alone or in combination for the treatment/eradication of clinically and agronomically relevant yeast pathogens/fungi.


Assuntos
Antifúngicos/farmacologia , Lactoferrina/farmacologia , Microdomínios da Membrana/efeitos dos fármacos , ATPases Translocadoras de Prótons/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Farmacorresistência Fúngica , Ergosterol/metabolismo , Filipina , Proteínas de Fluorescência Verde/análise , Microdomínios da Membrana/química , Mutação Puntual , ATPases Translocadoras de Prótons/biossíntese , ATPases Translocadoras de Prótons/genética , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/biossíntese , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestrutura , Proteínas de Saccharomyces cerevisiae/biossíntese , Proteínas de Saccharomyces cerevisiae/genética , Vacúolos/efeitos dos fármacos , Vacúolos/enzimologia , beta-Ciclodextrinas/farmacologia
9.
Med Res Rev ; 41(4): 1927-1964, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33483985

RESUMO

The control of the intracellular pH is vital for the survival of all organisms. Membrane transporters, both at the plasma and intracellular membranes, are key players in maintaining a finely tuned pH balance between intra- and extracellular spaces, and therefore in cellular homeostasis. V-ATPase is a housekeeping ATP-driven proton pump highly conserved among prokaryotes and eukaryotes. This proton pump, which exhibits a complex multisubunit structure based on cell type-specific isoforms, is essential for pH regulation and for a multitude of ubiquitous and specialized functions. Thus, it is not surprising that V-ATPase aberrant overexpression, mislocalization, and mutations in V-ATPase subunit-encoding genes have been associated with several human diseases. However, the ubiquitous expression of this transporter and the high toxicity driven by its off-target inhibition, renders V-ATPase-directed therapies very challenging and increases the need for selective strategies. Here we review emerging evidence linking V-ATPase and both inherited and acquired human diseases, explore the therapeutic challenges and opportunities envisaged from recent data, and advance future research avenues. We highlight the importance of V-ATPases with unique subunit isoform molecular signatures and disease-associated isoforms to design selective V-ATPase-directed therapies. We also discuss the rational design of drug development pipelines and cutting-edge methodological approaches toward V-ATPase-centered drug discovery. Diseases like cancer, osteoporosis, and even fungal infections can benefit from V-ATPase-directed therapies.


Assuntos
ATPases Vacuolares Próton-Translocadoras , Descoberta de Drogas , Humanos , ATPases Vacuolares Próton-Translocadoras/metabolismo
10.
Tree Physiol ; 41(6): 912-926, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-32348507

RESUMO

Vegetative propagation through somatic embryogenesis is an effective method to produce elite varieties and can be applied as a tool to study the response of plants to different stresses. Several studies show that environmental changes during embryogenesis could determine future plant development. Moreover, we previously reported that physical and chemical conditions during somatic embryogenesis can determine the protein, hormone and metabolite profiles, as well as the micromorphological and ultrastructural organization of embryonal masses and somatic embryos. In this sense, phytohormones are key players throughout the somatic embryogenesis process as well as during numerous stress-adaptation responses. In this work, we first applied different high-temperature regimes (30 °C, 4 weeks; 40 °C, 4 days; 50 °C, 5 min) during induction of Pinus radiata D. Don somatic embryogenesis, together with control temperature (23 °C). Then, the somatic plants regenerated from initiated embryogenic cell lines and cultivated in greenhouse conditions were subjected to drought stress and control treatments to evaluate survival, growth and several physiological traits (relative water content, water potential, photosynthesis, stomatal conductance and transpiration). Based on those preliminary results, even more extreme high-temperature regimes were applied during induction (40 °C, 4 h; 50 °C, 30 min; 60 °C, 5 min) and the corresponding cytokinin profiles of initiated embryonal masses from different lines were analysed. The results showed that the temperature regime during induction had delayed negative effects on drought resilience of somatic plants as indicated by survival, photosynthetic activity and water- use efficiency. However, high temperatures for extended periods of time enhanced subsequent plant growth in well-watered conditions. High-temperature regime treatments induced significant differences in the profile of total cytokinin bases, N6-isopentenyladenine, cis-zeatin riboside and trans-zeatin riboside. We concluded that phytohormones could be potential regulators of stress-response processes during initial steps of somatic embryogenesis and that they may have delayed implications in further developmental processes, determining the performance of the generated plants.


Assuntos
Pinus , Citocininas , Secas , Reguladores de Crescimento de Plantas , Temperatura
11.
Chem Biol Drug Des ; 97(4): 893-903, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314617

RESUMO

Breast cancer diagnosis remains a challenge, mostly due to its heterogeneity. This reality translates in delayed treatments, increasing treatment aggressiveness and lower chances of overall survival. The conventional detection techniques, although becoming increasingly sophisticated each year, still lack the ability to provide reliable conclusions without being time consuming, expensive, and uncomfortable for the patients. The identification of novel biomarkers for breast cancer research is therefore of utmost relevance for an early diagnosis. Moreover, breast cancer-specific peptide moieties can be used to develop novel targeted drug delivery systems. In this work, we used phage display to identify a novel peptide with specificity to the SK-BR-3 breast cancer cell line. Cytometry assays confirmed its specificity, while bioinformatics and docking studies predicted the potential biomarkers at the SK-BR-3 cells' surface. These findings can be potentially useful in the clinical context, contributing to more specific and targeted therapeutic solutions against HER2-positive breast cancer subtypes.


Assuntos
Peptídeos/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor 1 de Quimiocina CX3C/química , Receptor 1 de Quimiocina CX3C/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Simulação de Acoplamento Molecular , Biblioteca de Peptídeos , Peptídeos/química , Ligação Proteica , Receptor da Anafilatoxina C5a/química , Receptor da Anafilatoxina C5a/metabolismo
12.
Plants (Basel) ; 9(12)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322106

RESUMO

Based on the hypothesis that embryo development is a crucial stage for the formation of stable epigenetic marks that could modulate the behaviour of the resulting plants, in this study, radiata pine somatic embryogenesis was induced at high temperatures (23 °C, eight weeks, control; 40 °C, 4 h; 60 °C, 5 min) and the global methylation and hydroxymethylation levels of emerging embryonal masses and somatic plants were analysed using LC-ESI-MS/ MS-MRM. In this context, the expression pattern of six genes previously described as stress-mediators was studied throughout the embryogenic process until plant level to assess whether the observed epigenetic changes could have provoked a sustained alteration of the transcriptome. Results indicated that the highest temperatures led to hypomethylation of both embryonal masses and somatic plants. Moreover, we detected for the first time in a pine species the presence of 5-hydroxymethylcytosine, and revealed its tissue specificity and potential involvement in heat-stress responses. Additionally, a heat shock protein-coding gene showed a down-regulation tendency along the process, with a special emphasis given to embryonal masses at first subculture and ex vitro somatic plants. Likewise, the transcripts of several proteins related with translation, oxidative stress response, and drought resilience were differentially expressed.

13.
Cells ; 9(8)2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751253

RESUMO

Lamina-associated polypeptide 1 (LAP1) is a nuclear envelope (NE) protein whose function remains poorly characterized. In a recent LAP1 protein interactome study, a putative regulatory role in the DNA damage response (DDR) has emerged and telomeric repeat-binding factor 2 (TRF2), a protein intimately associated with this signaling pathway, was among the list of LAP1 interactors. To gain insights into LAP1's physiological properties, the interaction with TRF2 in human cells exposed to DNA-damaging agents was investigated. The direct LAP1:TRF2 binding was validated in vitro by blot overlay and in vivo by co-immunoprecipitation after hydrogen peroxide and bleomycin treatments. The regulation of this protein interaction by LAP1 phosphorylation was demonstrated by co-immunoprecipitation and mass spectrometry following okadaic acid exposure. The involvement of LAP1 and TRF2 in the DDR was confirmed by their increased nuclear protein levels after bleomycin treatment, evaluated by immunoblotting, as well as by their co-localization with DDR factors at the NE and within the nucleoplasm, assessed by immunocytochemistry. Effectively, we showed that the LAP1:TRF2 complex is established during a cellular response against DNA damage. This work proposes a novel functional role for LAP1 in the DDR, revealing a potential biological mechanism that may be disrupted in LAP1-associated pathologies.


Assuntos
Núcleo Celular/metabolismo , Dano ao DNA/efeitos dos fármacos , Proteínas de Choque Térmico HSC70/metabolismo , Complexos Multiproteicos/metabolismo , Proteína 2 de Ligação a Repetições Teloméricas/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Bleomicina/farmacologia , Células HeLa , Histonas/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Membrana Nuclear/metabolismo , Fosforilação , Ligação Proteica , Transdução de Sinais
14.
Artigo em Inglês | MEDLINE | ID: mdl-32540973

RESUMO

Most microbes live in spatially confined subpopulations. Under spatial structure conditions, the efficacy of natural selection is often reduced (relative to homogeneous conditions) due to the increased importance of genetic drift and local competition. Additionally, under spatial structure conditions, the fittest genotype may not always be the one with better access to the heterogeneous distribution of nutrients. The effect of radial expansion may be particularly relevant for the elimination of antibiotic resistance mutations, as their dynamics within bacterial populations are strongly dependent on their growth rate. Here, we use Escherichia coli to systematically compare the allele frequency of streptomycin, rifampin, and fluoroquinolone single and double resistance mutants after 24 h of coexistence with a susceptible strain under radial expansion (local competition) and homogeneous (global competition) conditions. We show that there is a significant effect of structure on the maintenance of double resistances which is not observed for single resistances. Radial expansion also facilitates the persistence of double resistances when competing against their single counterparts. Importantly, we found that spatial structure reduces the rate of compensation of the double mutant RpsLK43T RpoBH526Y and that a strongly compensatory mutation in homogeneous conditions becomes deleterious under spatial structure conditions. Overall, our results unravel the importance of spatial structure for facilitating the maintenance and accumulation of multiple resistances over time and for determining the identity of compensatory mutations.


Assuntos
Farmacorresistência Bacteriana , Escherichia coli , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Fluoroquinolonas/farmacologia , Mutação , Rifampina/farmacologia , Estreptomicina/farmacologia
15.
Cad. pesqui ; 50(176): 475-493, abr.-jun. 2020. tab, graf
Artigo em Português | LILACS-Express | LILACS, Index Psicologia - Periódicos | ID: biblio-1132921

RESUMO

Resumo Este trabalho apresenta uma investigação sobre o desempenho dos estudantes brasileiros em Matemática no Pisa de 2003 e 2012. O objetivo foi verificar em qual conteúdo avaliado os estudantes apresentaram melhor desempenho e dispersão positiva na escala de níveis da avaliação. A estratégia empírica adotada foi descritiva e comparativa. Foram analisados relatórios do Inep (Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira) e da OCDE/Pisa para compor a base de dados para análise comparativa das duas aplicações da prova. Os resultados apontam que os estudantes brasileiros apresentaram melhor desempenho e a mais significativa distribuição na escala Pisa em Indeterminação e Dados ou Probabilidade. Contudo o desempenho dos estudantes brasileiros, influenciado por uma multiplicidade de fatores, ainda está longe de atingir os níveis da OCDE.


Abstract This study presents an investigation on the performance of Brazilian students in Mathematics in Pisa 2003 and 2012. Our goal was to identify the assessed content in which the students had their best performance and most significant dispersion in the scale of assessment levels. Our empirical study consisted of descriptive and comparative analyses. Reports from Inep (Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira) and OECD/Pisa were analyzed to make up the database for comparing the two editions of the test. The results show that Brazilian students had their best performance and most significant distribution on the Pisa scale in Indetermination and Data or Probability. However, the performance of Brazilian students, influenced by innumerous factors, is still far below OECD levels.


Résumé Cet article présente une recherche sur la performance des élèves brésiliens en mathématiques dans au Pisa 2003 et 2012. L'objectif était de vérifier quels étaient les contenus évalués dans lesquels les élèves avaient obtenu une meilleure performance et dispersion positive sur l'échelle des niveaux d'évaluation. La stratégie empirique adoptée a été d'ordre descriptif et comparatif. Des rapports de l'Inep (Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira) et de l' OCDE/Pisa ont été analysés pour composer la base de données de l'analyse comparative des deux épreuves du test. Les résultats indiquent que, sur l'échelle Pisa, les élèves brésiliens ont présenté une meilleure performance et la distribution la plus marquée en Indétermination et en Données et Probabilité. Cependant, dû à une multitude de facteurs, le score des élèves brésiliens est encore loin d'atteindre les niveaux de l'OCDE.


Resumen Este trabajo presenta una investigación sobre el desempeño de los estudiantes brasileños en Matemática en el Pisa de 2003 y 2012. El objetivo fue verificar en cuál contenido evaluado los estudiantes presentaron mejor desempeño y dispersión positiva en la escala de niveles de evaluación. La estrategia empírica adoptada fue descriptiva y comparativa. Fueron analizados informes del Inep (Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira) y de la OCDE/Pisa para componer la base de datos para análisis comparativa de las dos aplicaciones de la prueba. Los resultados apuntan que los estudiantes brasileños presentaron mejor desempeño y la más significativa distribución en la escala Pisa en Indeterminación y Datos o Probabilidad. Aun considerando esto, el desempeño de los estudiantes brasileños, influenciado por una multiplicidad de factores, todavía esta lejos de alcanzar los niveles de la OCDE.

17.
Aging Cell ; 19(5): e13143, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32291910

RESUMO

The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Therefore, during aging and premature aging, several cellular alterations occur, including nuclear-specific changes, particularly, altered nuclear transport, increased genomic instability induced by DNA damage, and telomere attrition. Here, we highlight and discuss proteins associated with nuclear transport dysfunction induced by aging, particularly nucleoporins, nuclear transport factors, and lamins. Moreover, changes in the structure of chromatin and consequent heterochromatin rearrangement upon aging are discussed. These alterations correlate with NE dysfunction, particularly lamins' alterations. Finally, telomere attrition is addressed and correlated with altered levels of nuclear lamins and nuclear lamina-associated proteins. Overall, the identification of molecular mechanisms underlying NE dysfunction, including upstream and downstream events, which have yet to be unraveled, will be determinant not only to our understanding of several pathologies, but as here discussed, in the aging process.


Assuntos
Senescência Celular , Membrana Nuclear/metabolismo , Membrana Nuclear/patologia , Animais , Núcleo Celular/metabolismo , Humanos
19.
Nat Immunol ; 20(12): 1644-1655, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31636468

RESUMO

Invariant natural killer T (iNKT) cells recognize activating self and microbial lipids presented by CD1d. CD1d can also bind non-activating lipids, such as sphingomyelin. We hypothesized that these serve as endogenous regulators and investigated humans and mice deficient in acid sphingomyelinase (ASM), an enzyme that degrades sphingomyelin. We show that ASM absence in mice leads to diminished CD1d-restricted antigen presentation and iNKT cell selection in the thymus, resulting in decreased iNKT cell levels and resistance to iNKT cell-mediated inflammatory conditions. Defective antigen presentation and decreased iNKT cells are also observed in ASM-deficient humans with Niemann-Pick disease, and ASM activity in healthy humans correlates with iNKT cell phenotype. Pharmacological ASM administration facilitates antigen presentation and restores the levels of iNKT cells in ASM-deficient mice. Together, these results demonstrate that control of non-agonistic CD1d-associated lipids is critical for iNKT cell development and function in vivo and represents a tight link between cellular sphingolipid metabolism and immunity.


Assuntos
Inflamação/imunologia , Células T Matadoras Naturais/imunologia , Doenças de Niemann-Pick/genética , Esfingomielina Fosfodiesterase/metabolismo , Esfingomielinas/imunologia , Timo/imunologia , Animais , Apresentação do Antígeno , Antígenos CD1d/metabolismo , Diferenciação Celular , Seleção Clonal Mediada por Antígeno , Terapia de Reposição de Enzimas , Humanos , Ativação Linfocitária , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esfingomielina Fosfodiesterase/genética , Esfingomielinas/metabolismo
20.
Eur J Case Rep Intern Med ; 6(7): 001177, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410360

RESUMO

Dumping syndrome (DS) is a debilitating entity with gastrointestinal and vasomotor symptoms due to rapid gastric emptying. It is a rare complication of Nissen fundoplication in adults. We report the case of a patient with oesophageal compressive symptoms (dysphagia, oesophageal food impaction and regurgitation) and frequent episodes of sweating and hypoglycaemia after a Nissen fundoplication to treat gastroesophageal reflux disease. Investigation revealed severe oesophagogastric stenosis and excluded insulinoma and other causes of hypoglycaemia. An oral glucose tolerance test and gastric emptying scintigraphy were performed, supporting the diagnosis of DS. LEARNING POINTS: Dumping syndrome following Nissen fundoplication is a rare condition in adults.Diagnosis requires exclusion of other causes of hypoglycaemia.First-line treatment is based on dietary modifications, although some patients may require pharmacological therapy.

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