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1.
PLoS Genet ; 19(12): e1011109, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38134228

RESUMO

The Muscleblind-like (MBNL) family is a highly conserved set of RNA-binding proteins (RBPs) that regulate RNA metabolism during the differentiation of various animal tissues. Functional insufficiency of MBNL affects muscle and central nervous system development, and contributes to the myotonic dystrophies (DM), a set of incurable multisystemic disorders. Studies on the regulation of MBNL genes are essential to provide insight into the gene regulatory networks controlled by MBNL proteins and to understand how dysregulation within these networks causes disease. In this study, we demonstrate the evolutionary conservation of an autoregulatory mechanism that governs the function of MBNL proteins by generating two distinct protein isoform types through alternative splicing. Our aim was to further our understanding of the regulatory principles that underlie this conserved feedback loop in a whole-organismal context, and to address the biological significance of the respective isoforms. Using an alternative splicing reporter, our studies show that, during development of the Caenorhabditis elegans central nervous system, the orthologous mbl-1 gene shifts production from long protein isoforms that localize to the nucleus to short isoforms that also localize to the cytoplasm. Using isoform-specific CRISPR/Cas9-generated strains, we showed that expression of short MBL-1 protein isoforms is required for healthy neuromuscular function and neurodevelopment, while expression of long MBL-1 protein isoforms is dispensable, emphasizing a key role for cytoplasmic functionalities of the MBL-1 protein. Furthermore, RNA-seq and lifespan analyses indicated that short MBL-1 isoforms are crucial regulators of miRNA expression and, in consequence, required for normal lifespan. In conclusion, this study provides support for the disruption of cytoplasmic RNA metabolism as a contributor in myotonic dystrophy and paves the way for further exploration of miRNA regulation through MBNL proteins during development and in disease models.


Assuntos
MicroRNAs , Distrofia Miotônica , Animais , Processamento Alternativo/genética , Caenorhabditis elegans/genética , MicroRNAs/genética , Distrofia Miotônica/genética , Isoformas de Proteínas/genética
2.
Nature ; 576(7786): 253-256, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31827290

RESUMO

Limiting the increase of CO2 in the atmosphere is one of the largest challenges of our generation1. Because carbon capture and storage is one of the few viable technologies that can mitigate current CO2 emissions2, much effort is focused on developing solid adsorbents that can efficiently capture CO2 from flue gases emitted from anthropogenic sources3. One class of materials that has attracted considerable interest in this context is metal-organic frameworks (MOFs), in which the careful combination of organic ligands with metal-ion nodes can, in principle, give rise to innumerable structurally and chemically distinct nanoporous MOFs. However, many MOFs that are optimized for the separation of CO2 from nitrogen4-7 do not perform well when using realistic flue gas that contains water, because water competes with CO2 for the same adsorption sites and thereby causes the materials to lose their selectivity. Although flue gases can be dried, this renders the capture process prohibitively expensive8,9. Here we show that data mining of a computational screening library of over 300,000 MOFs can identify different classes of strong CO2-binding sites-which we term 'adsorbaphores'-that endow MOFs with CO2/N2 selectivity that persists in wet flue gases. We subsequently synthesized two water-stable MOFs containing the most hydrophobic adsorbaphore, and found that their carbon-capture performance is not affected by water and outperforms that of some commercial materials. Testing the performance of these MOFs in an industrial setting and consideration of the full capture process-including the targeted CO2 sink, such as geological storage or serving as a carbon source for the chemical industry-will be necessary to identify the optimal separation material.

3.
Nat Mater ; 21(12): 1419-1425, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36229651

RESUMO

The heat capacity of a material is a fundamental property of great practical importance. For example, in a carbon capture process, the heat required to regenerate a solid sorbent is directly related to the heat capacity of the material. However, for most materials suitable for carbon capture applications, the heat capacity is not known, and thus the standard procedure is to assume the same value for all materials. In this work, we developed a machine learning approach, trained on density functional theory simulations, to accurately predict the heat capacity of these materials, that is, zeolites, metal-organic frameworks and covalent-organic frameworks. The accuracy of our prediction is confirmed with experimental data. Finally, for a temperature swing adsorption process that captures carbon from the flue gas of a coal-fired power plant, we show that for some materials, the heat requirement is reduced by as much as a factor of two using the correct heat capacity.


Assuntos
Estruturas Metalorgânicas , Nanoporos , Carvão Mineral , Temperatura Alta , Centrais Elétricas , Carbono
4.
Int J Eat Disord ; 56(7): 1444-1448, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37039564

RESUMO

OBJECTIVE: Disgust is an established mechanism driving restrictive eating behavior. Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder diagnosis characterized by extremely selective eating with three hypothesized presentations. It has been suggested that disgust is significantly associated with ARFID; however, there is limited empirical research to support this hypothesis. This study explores relationships between food-specific disgust, ARFID symptoms, and ARFID presentations. METHOD: Undergraduate students (n = 443, Mage = 19.14 years [SD = 1.25], 50.1% female, 52.7% White) completed a validated measure of food-specific disgust and an established self-report screening tool for the likely presence of ARFID and hypothesized ARFID presentations. RESULTS: Sixty-nine (14.5%) participants screened positively for the likely presence of ARFID. Food disgust did not differ between those who did and did not screen positively for ARFID (p > .05). Within the subsample of those screening positive for ARFID, disgust was not related to any of the three hypothesized presentations of ARFID (all p > .05). DISCUSSION: Our results did not show a significant association between disgust and positive ARFID screen or any of the hypothesized ARFID presentations. Importantly, these negative findings were obtained using validated screening tools for ARFID. Future research should seek to replicate these findings in clinical samples to further inform treatment. PUBLIC SIGNIFICANCE: Avoidant/restrictive food intake disorder (ARFID) is associated with significant medical and psychosocial complications, but the mechanism involved in its development and maintenance remain poorly understood. Findings from this study of college students screening positively for ARFID suggests that food disgust in not a key driver of ARFID symptoms. Exposure-based approaches, which are generally not thought to be effective in targeting disgust, may thus be appropriate in the treatment of ARFID.


Assuntos
Transtorno Alimentar Restritivo Evitativo , Asco , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Feminino , Adulto Jovem , Adulto , Masculino , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Autorrelato , Ingestão de Alimentos , Estudos Retrospectivos
5.
BMC Cancer ; 22(1): 536, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35549912

RESUMO

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Neoplasias Retais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias Colorretais/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Hipertermia Induzida/métodos , Quimioterapia Intraperitoneal Hipertérmica , Mitomicina/uso terapêutico , Neoplasias Peritoneais/secundário , Estudos Prospectivos , Neoplasias Retais/terapia , Taxa de Sobrevida
6.
Water Resour Res ; 58(6): e2021WR030729, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35859620

RESUMO

Usually, models describing flow and transport for sub-surface engineering processes at the Darcy-scale do not take into consideration the effects of pore-scale flow regimes and fluid connectivity on average flow functions. In this article, we investigate the impact of wettability on pore-scale flow regimes. We show that fluid connectivity at the pore scale has a significant impact on average flow kinetics and therefore its contribution should not be ignored. Immiscible two-phase flow simulations were performed in a two-dimensional model of a Berea sandstone rock for wettability conditions ranging from moderately water-wet to strongly oil-wet. The simulation results show that wettability has a strong impact on invading fluid phase connectivity, which subsequently influences flow transport resistance. The effect of invading-phase connectivity and ganglion dynamics (GD) on two-phase displacement kinetics was also investigated. It was found that invading phase connectivity decreases away from the neutrally wet (intermediate wet) state. This study provides evidence that GD accelerate fluid flow transport kinetics during immiscible displacement processes. Lastly, the impact of wettability on fluid displacement efficiency and residual saturations was investigated. Maximum displacement efficiency occurred at the neutrally wet state.

7.
Rev Argent Microbiol ; 54(4): 314-317, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-35688718

RESUMO

Desulfovibrio spp. are strict anaerobes that are ubiquitous in nature. They can reside in the human or animal gastrointestinal tract and, as they are also environmental bacteria, may be present in soil and water. They can persist asymptomatically in the intestine or behave as opportunistic pathogens associated with primary bacteremia and intraabdominal infections. Several Desulfovibrio spp. infections may be underestimated due to their slow growth rate and because many laboratories do not routinely perform anaerobic cultures. Simple tests such as motility detection on a fresh subculture, Gram stain to confirm cell morphology, presence of H2S in SIM agar and production of a red fluorescence in alkaline pH under UV light would be indicative of Desulfovibrio spp. Here we report the case of Desulfovibrio desulfuricans bacteremia in a woman with clinical picture of abdominal sepsis due to gangrenous appendicitis with multiple organ failure.


Assuntos
Bacteriemia , Desulfovibrio desulfuricans , Infecções Intra-Abdominais , Feminino , Humanos , Bacteriemia/microbiologia
8.
Am J Med Genet B Neuropsychiatr Genet ; 189(5): 163-173, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35785430

RESUMO

We present innovative research practices in psychiatric genetic studies to ensure representation of individuals from diverse ancestry, sex assigned at birth, gender identity, age, body shape and size, and socioeconomic backgrounds. Due to histories of inappropriate and harmful practices against marginalized groups in both psychiatry and genetics, people of certain identities may be hesitant to participate in research studies. Yet their participation is essential to ensure diverse representation, as it is incorrect to assume that the same genetic and environmental factors influence the risk for various psychiatric disorders across all demographic groups. We present approaches developed as part of the Eating Disorders Genetics Initiative (EDGI), a study that required tailored approaches to recruit diverse populations across many countries. Considerations include research priorities and design, recruitment and study branding, transparency, and community investment and ownership. Ensuring representation in participants is costly and funders need to provide adequate support to achieve diversity in recruitment in prime awards, not just as supplemental afterthoughts. The need for diverse samples in genetic studies is critical to minimize the risk of perpetuating health disparities in psychiatry and other health research. Although the EDGI strategies were designed specifically to attract and enroll individuals with eating disorders, our approach is broadly applicable across psychiatry and other fields.


Assuntos
Identidade de Gênero , Pesquisa , Feminino , Humanos , Recém-Nascido , Masculino
9.
Am J Transplant ; 21(4): 1597-1602, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33319435

RESUMO

Heart transplantation from controlled donation after the circulatory determination of death (cDCDD) may help to increase the availability of hearts for transplantation. During 2020, four heart transplants were performed at three different Spanish hospitals based on the use of thoraco-abdominal normothermic regional perfusion (TA-NRP) followed by cold storage (CS). All donors were young adults <45 years. The functional warms ischemic time ranged from 8 to 16 minutes. In all cases, the heart recovered sinus rhythm within 1 minute of TA-NRP. TA-NRP was weaned off or decreased <1L within 25 minutes. No recipient required mechanical support after transplantation and all were immediately extubated and discharged home (median hospital stay: 21 days) with an excellent outcome. Four livers, eight kidneys, and two pancreata were also recovered and transplanted. All abdominal grafts recipients experienced an excellent outcome. The use of TA-NRP makes heart transplantation feasible and allows assessing heart function before organ procurement without any negative impact on the preservation of abdominal organs. The use of TA-NRP in cDCDD heart donors in conjunction with cold storage following retrieval can eliminate the need to use ex situ machine perfusion devices, making cDCDD heart transplantation economically possible in other countries.


Assuntos
Transplante de Coração , Obtenção de Tecidos e Órgãos , Morte , Humanos , Preservação de Órgãos , Perfusão , Doadores de Tecidos , Adulto Jovem
10.
Ann Surg Oncol ; 28(7): 3714-3721, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33247362

RESUMO

INTRODUCTION: The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. METHODS: This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery. RESULTS: Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. CONCLUSIONS: Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Comorbidade , Feminino , Hospitais , Humanos , Estudos Prospectivos , Tempo para o Tratamento
11.
Microbiology (Reading) ; 166(1): 85-92, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625834

RESUMO

Gene regulation in yeast occurs at the transcription level, i.e. the basal level of expression is very low and increased transcription requires gene-specific transcription factors allowing the recruitment of basal transcriptional machinery. Saccharomyces cerevisiae BAP2 gene encodes the permease responsible for most uptake of leucine, valine and isoleucine, amino acids that this yeast can use as nitrogen sources. Moreover, BAP2 expression is known to be induced by the presence of amino acids such as leucine. In this context, the results presented in this paper show that BAP2 is an inducible gene in the presence of nitrogen-non-preferred source proline but exhibits high constitutive non-inducible expression in nitrogen-preferred source ammonium. BAP2 expression is regulated by the SPS sensor system and transcription factors Leu3, Gcn4 and Dal81. This can be achieved or not through a direct binding to the promoter depending on the quality of the nitrogen source. We further demonstrate here that an interaction occurs in vivo between Uga3 ‒ the transcriptional activator responsible for γ-aminobutyric acid (GABA)-dependent induction of the GABA genes ‒ and the regulatory region of the BAP2 gene, which leads to an increase in BAP2 transcription.


Assuntos
Sistemas de Transporte de Aminoácidos/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Proteínas de Ligação a DNA/genética , Regulação Fúngica da Expressão Gênica , Nitrogênio/metabolismo , Regiões Promotoras Genéticas , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética
12.
Int J Eat Disord ; 53(11): 1844-1854, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32844425

RESUMO

BACKGROUND: Individuals with eating disorders (EDs) have increased rates of major depressive disorder (MDD) and anxiety disorders. Yet, few studies have investigated rates of EDs and their symptoms in individuals presenting with MDD/anxiety disorders. Identifying potential disordered eating in people with MDD/anxiety disorders is important because even subclinical disordered eating is associated with reduced quality of life, and undiagnosed eating pathology may hinder treatment progress for both MDD/anxiety disorders and comorbid EDs. METHOD: We compared rates of EDs (anorexia nervosa, bulimia nervosa, binge-eating disorder, and other specified feeding and eating disorders) and their symptoms in 130 women with, and 405 women without, lifetime MDD or an anxiety disorder (generalized anxiety disorder, obsessive-compulsive disorder, social phobia, specific phobia, panic disorder, agoraphobia, or post-traumatic stress disorder) recruited from the population-based Michigan State University Twin Registry. Lifetime ED and MDD/anxiety diagnoses, and lifetime clinically significant disordered eating behaviors (e.g., binge eating, excessive exercise) were assessed using the Structured Clinical Interview for DSM-IV (SCID). RESULTS: Among participants with lifetime MDD or any anxiety disorder, 13% met criteria for a lifetime ED and 39% reported engaging in at least one lifetime clinically significant disordered eating behavior (e.g., binge eating) on the SCID. In contrast, only 3% of participants without a history of MDD/an anxiety disorder met criteria for a lifetime ED, and only 11% reported lifetime clinically significant disordered eating behavior. DISCUSSION: Our findings suggest that women with MDD and anxiety disorders have elevated rates of EDs, and it is therefore imperative to screen for disordered eating in these populations.


Assuntos
Transtornos de Ansiedade/complicações , Transtorno Depressivo Maior/complicações , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Adolescente , Adulto , Transtornos de Ansiedade/psicologia , Comorbidade , Transtorno Depressivo Maior/psicologia , Transtornos da Alimentação e da Ingestão de Alimentos/patologia , Feminino , Humanos , Qualidade de Vida , Adulto Jovem
13.
J Sci Food Agric ; 100(4): 1577-1587, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31769028

RESUMO

BACKGROUND: Arbuscular mycorrhizal (AM) fungi establish symbioses with most agricultural plants and improves growth under soil stress conditions. The present study aimed to evaluate the functional contribution of 2 AM fungal inocula (a native consortium isolated from saline soils of the Atacama Desert, 'HMC', and a reference inoculum Claroideoglomus claroideum, 'Cc') on the growth and antioxidant compounds of two cultivars of lettuce (Lactuca sativa cvs. 'Grand Rapids' and 'Lollo Bionda') at increasing salt stress conditions (0, 40, and 80 mmol L-1 NaCl). At 60 days of plant growth, the symbiotic development, biomass production, lipid peroxidation, proline content, antioxidant enzymes, phenolic compound profiles and antioxidant activity were evaluated. RESULTS: The 2 AM inocula differentially colonized the roots of Grand Rapids and Lollo Bionda lettuce plants. The AM symbioses increased proline synthesis and superoxide dismutase, catalase and ascorbate peroxidase activities and diminished phenolic compound synthesis and oxidative damage in lettuce, which was related positively to a higher growth of inoculated plants under salt exposure. The higher concentration of phenolic compounds induced by salinity in non-inoculated plants was associated with high oxidative stress and low fresh biomass production. CONCLUSION: Modulation of salinity stress in lettuce by AM root colonization is a result of changes of antioxidant enzymatic systems that reduce oxidative damage and sustain growth. The application of AM fungi to improve crop production by means of directed inoculation with efficient AM fungal strains may enhance lettuce production on soils plagued with salinity worldwide. © 2019 Society of Chemical Industry.


Assuntos
Inoculantes Agrícolas/fisiologia , Antioxidantes/metabolismo , Glomeromycota/fisiologia , Lactuca/microbiologia , Lactuca/fisiologia , Micorrizas/fisiologia , Catalase/genética , Catalase/metabolismo , Lactuca/genética , Lactuca/crescimento & desenvolvimento , Estresse Oxidativo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tolerância ao Sal , Cloreto de Sódio/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
14.
Rev Argent Microbiol ; 52(2): 101-106, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-31628000

RESUMO

During the periods 2000-2004 and 2014-2015, Neisseria meningitidis was investigated in men who have sex with men, 1143 and 544 respectively, who consulted in the sexually-transmitted disease program. Prevalence, serogroup distribution and susceptibility to antibiotics were determined. Pharyngeal, rectal and urethral swabs were cultivated on selective Thayer-Martin modified medium. The identification was performed by biochemical tests and mass spectrometry by MALDI-TOF. Serogroups B, C, W and Y were investigated by PCR in 85 isolates recovered from the pharynx belonging to the second period. MICs of penicillin, ceftriaxone, rifampicin, azithromycin and ciprofloxacin were determined for 66 and 102 isolates from periods 1 and 2 respectively, according to CLSI. The prevalence of N. meningitidis was 17.8% and 28.1%, in periods 1 and 2 respectively; the isolates were mainly recovered from the pharynx. The distribution of serogroups was B 31.5%; Y 7.6%; W 3.3% and 9.8% non-capsulated and the rest would belong to other serogroups. Isolates classified as intermediate to penicillin were 34.8% and 63.7% (first and second periods, respectively); moreover, 11.8% of the isolates from the second period were resistant. All isolates were susceptible to ceftriaxone, to ciprofloxacin (except 3 isolates with MIC values between 0.25 and 0.5µg/ml), 3% were resistant to rifampicin and 2% were not susceptible to azithromicin. The prevalence of N. meningitidis carriage in men who have sex with men was high with a high rate of penicillin non-susceptible isolates. B was the prevalent serogroup.


Assuntos
Homossexualidade Masculina , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/isolamento & purificação , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Masculino , Infecções Meningocócicas/tratamento farmacológico , Infecções Meningocócicas/epidemiologia , Testes de Sensibilidade Microbiana , Neisseria meningitidis/classificação , Neisseria meningitidis/efeitos dos fármacos , Prevalência , Sorogrupo
15.
Scand J Immunol ; 90(3): e12802, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269269

RESUMO

Glucose and nutrient uptake is essential in supporting T cell activation and is increased upon CD3/CD28 stimulation. As T cells from pleural effusions secondary to lung cancer show impaired function, we hypothesized that these cells might have altered expression of nutrient transporters. Here, we analysed by flow cytometry the expression of the transferrin receptor CD71, amino acid transporter CD98 and glucose transporter Glut1 and glucose uptake in pleural effusion-derived T cells from lung cancer patients, after stimulation via CD3/CD28 under normoxia or hypoxia (2% O2 ). We compared the response of T cells from pleural effusions secondary to lung cancer with that of T cells from nonmalignant effusions. In memory T cells from both groups, anti-CD3/CD28-stimulation under normoxia upregulated CD98 and CD71 expression (measured as median fluorescence intensity, MFI) in comparison with anti-CD3-stimulation. Costimulation under hypoxia tended to increase CD98 expression compared to CD3-stimulation in memory T cells from both groups. Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti-CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions. Consequently, glucose uptake by memory T cells from the cancer group was not increased after CD3/CD28 stimulation under hypoxia, implying that their glycolytic metabolism is defective. As this process is required for inducing an antitumoural response, our study suggests that memory T cells are rendered dysfunctional and are unable to eliminate lung tumour cells.


Assuntos
Antígenos CD28/metabolismo , Complexo CD3/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glucose/metabolismo , Memória Imunológica/imunologia , Neoplasias Pulmonares/metabolismo , Derrame Pleural/metabolismo , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Derrame Pleural/imunologia , Linfócitos T/metabolismo
16.
Nature ; 493(7434): 694-8, 2013 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-23364702

RESUMO

Genetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute and Dicer as essential cofactors that process and present small RNAs to their targets. Well-validated small RNA pathway cofactors such as these show distinctive patterns of conservation or divergence in particular animal, plant, fungal and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA- or short interfering RNA (siRNA)-mediated repression in Caenorhabditis elegans and Drosophila melanogaster, and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins. The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction data sets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about one-half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small-RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in those species.


Assuntos
Caenorhabditis elegans/genética , Variação Genética , Filogenia , RNA Interferente Pequeno/genética , Animais , Caenorhabditis elegans/classificação , Proteínas de Caenorhabditis elegans/genética , Eucariotos/classificação , Eucariotos/genética , Genoma/genética , MicroRNAs/genética , Proteoma , Splicing de RNA
17.
J Sci Food Agric ; 99(5): 2404-2410, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30357837

RESUMO

BACKGROUND: Strawberries are consumed worldwide. In Chile, strawberry production has been established in Andisols, were phosphorus is scarce. Traditional fertilization (TF) and organic fertilization (OF) have both been established there. This study examined their impact on the polyphenolic content of strawberries. RESULTS: Two anthocyanins were identified by high performance liquid chromatography with diode array detection coupled to mass spectrometry (HPLC-DAD-ESI-MS/MS). The average total anthocyanin concentrations were found to be 651 mg kg-1 fresh weight in 100% OF, which represents a 56% increase compared to fruits that were not fertilized. In the case of flavonols, only quercetin-rhamnoside was identified, and its concentration reached 14.6 mg kg-1 with 100% OF. The ascorbic acid concentration reached 0.54 g kg-1 in 50% TF (a 20% increase over fruits without fertilization, WF). The antioxidant activities slightly increased in the fruits subjected to TF and OF in comparison with WF treatment. CONCLUSION: These results support a management strategy for obtaining the best quality and potential beneficial effects in health by increasing anthocyanins and other polyphenols under OF. © 2018 Society of Chemical Industry.


Assuntos
Antocianinas/química , Antioxidantes/química , Produção Agrícola/métodos , Fertilizantes/análise , Flavonóis/química , Fragaria/química , Chile , Cromatografia Líquida de Alta Pressão , Fragaria/crescimento & desenvolvimento , Frutas/química , Frutas/crescimento & desenvolvimento , Agricultura Orgânica/métodos , Polifenóis/química
18.
J Sci Food Agric ; 99(3): 1397-1404, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30120790

RESUMO

BACKGROUND: The main methods used to increase the yield and quality of strawberry fruit produced in acidic soils with low P availability include root colonization by arbuscular mycorrhizal (AM) fungi and adjusting the type of P supplementation by means of traditional (TF) or organic (OF) fertilization, and adjusting nutrient doses. In this study, the antioxidant properties of strawberry fruit were evaluated under different treatments of fertilization (TF or OF) and different doses of P supplied at planting (0, 50 or 100% of the agronomic recommendation) and in the presence or absence of AM fungus as a bioinoculant. RESULTS: Fruits without fertilization treatments and with TF presented with higher anthocyanin concentrations. In general, higher values were obtained without AM colonization. However, spectrophotometric tests showed the highest activity and concentration in the AM-inoculated treatments. It is likely that phenolic compounds other than anthocyanins are present in the extracts. These other compounds could not be identified by the method used but could be detected by the Folin-Ciocalteu method. CONCLUSION: This study provides information that allows for improvements in strawberry fruit quality by agronomic management, with a potential beneficial effect on the health of consumers. © 2018 Society of Chemical Industry.


Assuntos
Inoculantes Agrícolas/fisiologia , Fertilizantes/análise , Fragaria/microbiologia , Frutas/química , Micorrizas/fisiologia , Antocianinas/análise , Antocianinas/metabolismo , Antioxidantes/análise , Antioxidantes/metabolismo , Fragaria/química , Fragaria/crescimento & desenvolvimento , Fragaria/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Nitrogênio/análise , Nitrogênio/metabolismo , Fenóis/análise , Fenóis/metabolismo , Fosfatos/análise , Fosfatos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia
19.
Rev Argent Microbiol ; 51(1): 26-31, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-29941157

RESUMO

Members of the viridans group streptococci (VGS) are the cause of local and invasive infections. Due to the severity of these infections and taking into account that reports regarding epidemiological aspects are scarce, the aims of this work were the identification and the study of the antibiotic susceptibility profiles of the isolates recovered from patients that were hospitalized in order to find out about the resistance level and the epidemiology of infections in which VGS are involved. A hundred and thirty two isolates identified as VGS were isolated at Hospital de Clínicas «José de San Martín¼ during the period 2011-2015. The identification was performed by biochemical test and mass spectrometry by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry. Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded. All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S. mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were susceptible. Only two isolates were resistant to levofloxacin, 27.2% to tetracycline and it was not found high level resistance to gentamycin (MIC range 0.5-32µg/ml). Resistance to erythromycin was 17.4% with no significant difference between M and MLS phenotypes. The most active antibiotics were in addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and linezolid. These results highlight the importance of the continuous surveillance of the infections caused by VGS in order to predict a correct antibiotic therapy.


Assuntos
Antibacterianos/farmacologia , Estreptococos Viridans/efeitos dos fármacos , Argentina , Farmacorresistência Bacteriana , Hospitalização , Hospitais de Ensino , Humanos , Testes de Sensibilidade Microbiana , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Saúde da População Urbana , Estreptococos Viridans/isolamento & purificação
20.
Aten Primaria ; 51(2): 105-117, 2019 02.
Artigo em Espanhol | MEDLINE | ID: mdl-30591207
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