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1.
PLoS Genet ; 17(1): e1008761, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33493158

RESUMO

Non-coding RNAs (ncRNAs), including the more recently identified Stable Unannotated Transcripts (SUTs) and Cryptic Unstable Transcripts (CUTs), are increasingly being shown to play pivotal roles in the transcriptional and post-transcriptional regulation of genes in eukaryotes. Here, we carried out a large-scale screening of ncRNAs in Saccharomyces cerevisiae, and provide evidence for SUT and CUT function. Phenotypic data on 372 ncRNA deletion strains in 23 different growth conditions were collected, identifying ncRNAs responsible for significant cellular fitness changes. Transcriptome profiles were assembled for 18 haploid ncRNA deletion mutants and 2 essential ncRNA heterozygous deletants. Guided by the resulting RNA-seq data we analysed the genome-wide dysregulation of protein coding genes and non-coding transcripts. Novel functional ncRNAs, SUT125, SUT126, SUT035 and SUT532 that act in trans by modulating transcription factors were identified. Furthermore, we described the impact of SUTs and CUTs in modulating coding gene expression in response to different environmental conditions, regulating important biological process such as respiration (SUT125, SUT126, SUT035, SUT432), steroid biosynthesis (CUT494, SUT053, SUT468) or rRNA processing (SUT075 and snR30). Overall, these data capture and integrate the regulatory and phenotypic network of ncRNAs and protein-coding genes, providing genome-wide evidence of the impact of ncRNAs on cellular homeostasis.


Assuntos
Redes Reguladoras de Genes/genética , RNA não Traduzido/genética , Transcrição Gênica , Transcriptoma/genética , Regulação Fúngica da Expressão Gênica/genética , Genoma Fúngico , Haploidia , Fenótipo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética
2.
Clin Gastroenterol Hepatol ; 21(10): 2597-2605.e2, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36731585

RESUMO

BACKGROUND & AIMS: Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD. METHODS: A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates. RESULTS: Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids. CONCLUSIONS: Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).


Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , PPAR alfa/agonistas , PPAR alfa/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Agonistas PPAR-gama , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Triglicerídeos , Colesterol
3.
BMC Pulm Med ; 23(1): 442, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968677

RESUMO

BACKGROUND: The SARS-CoV2 pandemic impacted many critically ill patients, causing sequelae, affecting lung function, and involving the musculoskeletal system. We evaluated the association between lung function and muscle quality index in severely ill post-COVID-19 patients. METHODS: A cross-sectional study was conducted on a post-COVID-19 cohort at a third-level center. The study included patients who had experienced severe-to-critical COVID-19. Anthropometric measurements, such as body mass index (BMI) and handgrip strength, were obtained to calculate the muscle quality index (MQI). Additionally, spirometry, measurements of expiratory and inspiratory pressure, and an assessment of DLCO in the lungs were performed. The MQI was categorized into two groups: low-MQI (below the 50th percentile) and high-MQI (above the 50th percentile), based on sex. Group differences were analyzed, and a multivariate linear regression analysis was performed to assess the association between respiratory function and MQI. RESULTS: Among the 748 patients analyzed, 61.96% required mechanical ventilation, and the median hospital stay was 17 days. In patients with a low MQI, it was observed that both mechanical respiratory function and DLCO were lower. The multivariate analysis revealed significantly lower findings in mechanical respiratory function among patients with a low MQI. CONCLUSION: The Low-MQI is an independent predictor associated with pulmonary function parameters in subjects with Post-COVID-19 syndrome.


Assuntos
COVID-19 , Sistema Musculoesquelético , Humanos , Força da Mão/fisiologia , Estudos Transversais , Síndrome de COVID-19 Pós-Aguda , RNA Viral , SARS-CoV-2 , Pulmão , Músculos
4.
Mol Biol Evol ; 38(12): 5437-5452, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34550394

RESUMO

Saccharomyces pastorianus is a natural yeast evolved from different hybridization events between the mesophilic S. cerevisiae and the cold-tolerant S. eubayanus. This complex aneuploid hybrid carries multiple copies of the parental alleles alongside specific hybrid genes and encodes for multiple protein isoforms which impart novel phenotypes, such as the strong ability to ferment at low temperature. These characteristics lead to agonistic competition for substrates and a plethora of biochemical activities, resulting in a unique cellular metabolism. Here, we investigated the transcriptional signature of the different orthologous alleles in S. pastorianus during temperature shifts. We identified temperature-dependent media-independent genes and showed that 35% has their regulation dependent on extracellular leucine uptake, suggesting an interplay between leucine metabolism and temperature response. The analysis of the expression of ortholog parental alleles unveiled that the majority of the genes expresses preferentially one parental allele over the other and that S. eubayanus-like alleles are significantly over-represented among the genes involved in the cold acclimatization. The presence of functionally redundant parental alleles may impact on the nature of protein complexes established in the hybrid, where both parental alleles are competing. Our expression data indicate that the majority of the protein complexes investigated in the hybrid are likely to be either exclusively chimeric or unispecific and that the redundancy is discouraged, a scenario that fits well with the gene balance hypothesis. This study offers the first overview of the transcriptional pattern of S. pastorianus and provides a rationalization for its unique industrial traits at the expression level.


Assuntos
Genoma Fúngico , Saccharomyces cerevisiae , Saccharomyces , Alelos , Cerveja , Fermentação , Saccharomyces/genética , Saccharomyces cerevisiae/genética , Temperatura
5.
Crit Rev Food Sci Nutr ; 62(16): 4371-4392, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33506690

RESUMO

Chronic diseases are responsible for approximately 71% global deaths. These are characterized by chronic low-grade inflammation and metabolic alterations. "Functional foods" have been attributed with anti-inflammatory properties, demonstrated in cell lines and murine models; however, studies in humans are inconclusive. The purpose of this systematic review is to identify clinical trials that analyzed changes in inflammatory and metabolic mediators, in response to consumption of specific functional foods. A total of 3581 trials were screened and 88 were included for this review. Foods identified to regulate inflammation included cranberries, grapes, pomegranate, strawberries, wheat, whole grain products, low fat dairy products, yogurt, green tea, cardamom, turmeric, soy foods, almonds, chia seeds, flaxseed, pistachios, algae oil, flaxseed oil and grape seed oil. Clinical trials that focus on a dietary pattern rich in functional foods are necessary to explore if the additive effect of these foods lead to more clinically relevant outcomes.


Assuntos
Dieta , Alimento Funcional , Animais , Doença Crônica , Humanos , Inflamação , Óleo de Semente do Linho , Camundongos
6.
BMC Pulm Med ; 22(1): 106, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346135

RESUMO

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation. Different factors that modify pulmonary function include age, sex, muscular strength, and a history of exposure to toxic agents. However, the impact of body composition compartments and sarcopenia on pulmonary function is not well-established. This study aimed to evaluate how body composition compartments and sarcopenia affect pulmonary function in COPD patients. METHODS: In a cross-sectional study, patients with a confirmed diagnosis of COPD, > 40 years old, and forced expiratory volume in the first second /forced vital capacity ratio (FEV1/FVC) < 0.70 post-bronchodilator were included. Patients with cancer, HIV, and asthma were excluded. Body composition was measured with bioelectrical impedance. Sarcopenia was defined according to EWGSOP2, and pulmonary function was assessed by spirometry. RESULTS: 185 patients were studied. The mean age was 72.20 ± 8.39 years; 55.14% were men. A linear regression adjusted model showed associations between body mass index, fat-free mass, skeletal muscle mass index, appendicular skeletal muscle mass index, and phase angle (PhA), and sarcopenia with FEV1 (%). As regards FVC (%), PhA and exercise tolerance had positive associations. CONCLUSION: Body composition, especially PhA, SMMI, ASMMI, and sarcopenia, has a significant impact on pulmonary function. Early detection of disturbances of these indexes enables the early application of such therapeutic strategies in COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Estudos Transversais , Humanos , Pulmão , Masculino , Pessoa de Meia-Idade
7.
Int J Mol Sci ; 23(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35955668

RESUMO

The quantification of low abundant membrane-binding proteins such as transcriptional factors and chaperones has proven difficult, even with the most sophisticated analytical technologies. Here, we exploit and optimise the non-invasive Fluorescence Correlation Spectroscopy (FCS) for the quantitation of low abundance proteins, and as proof of principle, we choose two interacting proteins involved in the fission of mitochondria in yeast, Fis1p and Mdv1p. In Saccharomyces cerevisiae, the recruitment of Fis1p and Mdv1p to mitochondria is essential for the scission of the organelles and the retention of functional mitochondrial structures in the cell. We use FCS in single GFP-labelled live yeast cells to quantify the protein abundance in homozygote and heterozygote cells and to investigate the impact of the environments on protein copy number, bound/unbound protein state and mobility kinetics. Both proteins were observed to localise predominantly at mitochondrial structures, with the Mdv1p bound state increasing significantly in a strictly respiratory environment. Moreover, a compensatory mechanism that controls Fis1p abundance upon deletion of one allele was observed in Fis1p but not in Mdv1p, suggesting differential regulation of Fis1p and Mdv1p protein expression.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
8.
Int J Gynecol Cancer ; 31(9): 1228-1235, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34353855

RESUMO

OBJECTIVE: Cervical cancer is the fourth most frequent neoplasm among women in terms of incidence and mortality. Health-related quality of life (HRQL) is an important outcome in oncology. The QLQ-CX24 instrument was developed to measure HRQL in patients with cervical cancer, and its Mexican-Spanish version had not been validated. METHODS: Between March 2018 and May 2019, Mexican women older than 18, with any-stage cervical cancer were invited to participate in the study. Patients answered the QLQ-C30 and QLQ-CX24 questionnaires. Current tests for psychometric and clinical validation were performed. RESULTS: Three hundred and thirty patients with cervical cancer were included in this study. All women invited to participate accepted and were included. The QLQ-CX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.001-0.847) and divergent validity (Spearman correlation coefficient <0.0001-0.45). Cronbach's alpha coefficients of the three multi-item scales were >0.7 (minimum 0.76, maximum 0.89). Four scales of the QLQ-CX24 distinguished patients in different clinical stages. The evaluation of responsiveness demonstrated that the peripheral neuropathy scale was sensitive to change over time during chemo-radiation therapy. Six scales of the QLQ-CX24 instrument were associated with survival. CONCLUSION: The Mexican-Spanish version of the QLQ-CX24 questionnaire is reliable and valid for the assessment of HRQL in patients with cervical cancer.


Assuntos
Qualidade de Vida/psicologia , Neoplasias do Colo do Útero/epidemiologia , Feminino , Humanos , México , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários , Neoplasias do Colo do Útero/psicologia
9.
Ecol Lett ; 23(4): 674-681, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32043741

RESUMO

Decades of research suggest that species richness depends on spatial characteristics of habitat patches, especially their size and isolation. In contrast, the habitat amount hypothesis predicts that (1) species richness in plots of fixed size (species density) is more strongly and positively related to the amount of habitat around the plot than to patch size or isolation; (2) habitat amount better predicts species density than patch size and isolation combined, (3) there is no effect of habitat fragmentation per se on species density and (4) patch size and isolation effects do not become stronger with declining habitat amount. Data on eight taxonomic groups from 35 studies around the world support these predictions. Conserving species density requires minimising habitat loss, irrespective of the configuration of the patches in which that habitat is contained.


Assuntos
Ecossistema
10.
Rev Invest Clin ; 72(4): 219-230, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064687

RESUMO

In the development of cervical cancer (CC), the immune response plays an essential role, from the elimination of human papillomavirus (HPV) infection to the response against the tumor. For optimal function of the immune response, various factors are required, one of the most important being an adequate nutrition. The complex interaction between nutrients and microbiota maintains the immune system in homeostasis and in case of infection, it provides the ability to fight against pathogen invasion, as occurs in HPV infection. The purpose of this article is to describe the role of diet, food, and specific nutrients in the immune response from the onset of infection to progression to precancerous lesions and CC, as well as the role of diet and nutrition during oncological treatment. The immunomodulatory role of microbiota is also discussed. A detailed analysis of the evidence leads us to recommend a nutritional pattern very similar to the Mediterranean diet or the prudent diet for an optimal immune response. Moreover, pre- and probiotics favorably modulate the microbiota and induce preventive and therapeutic effects against cancer.


Assuntos
Imunidade , Estado Nutricional , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Dieta , Feminino , Microbioma Gastrointestinal , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/terapia
11.
Rev Invest Clin ; 70(3): 126-129, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29943774

RESUMO

Radiotherapy is a fundamental part of the treatment of pelvic neoplasms. Up to 90% of patients develop gastrointestinal symptoms as a result of acute injury to the small and large intestine, particularly in the mucosa. Radiotherapy leads to atrophy of the intestinal epithelium, acute crypt inflammation, inflammatory infiltration of the epithelium, malabsorption of lactose, and biliary salts as well as alterations in pancreatic enzymes and biliary salts, resulting in the malabsorption syndrome and dysbiosis. The most commonly reported symptoms of pelvic radiation disease include changes in bowel habits (94%), decreased fecal consistency (80%), frequency of bowel movements (74%), bowel urgency (39%), and fecal incontinence (37%). Although nutritional interventions with dietary modifications have been reported to prevent and treat gastrointestinal symptoms, the evidence remains inconclusive.


Assuntos
Dieta , Gastroenteropatias/etiologia , Neoplasias Pélvicas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Trato Gastrointestinal/fisiopatologia , Humanos , Lesões por Radiação/epidemiologia
12.
Rev Invest Clin ; 70(3): 112-116, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29943771

RESUMO

Mexico has seen an increase in cancer prevalence in its entire population as well as particular age ranges, predominantly the older segment. The most frequently reported pelvic cancers in Mexico are cervical, endometrial, bladder, prostate, rectum, and anal canal. Approximately 80% of the population diagnosed with pelvic cancers present with locally advanced tumors and require concomitant chemoradiotherapy, sequential chemoradiotherapy, or radiotherapy alone. The toxicity of any of these treatment modalities may be manifested as intestinal injury, a significant problem that can compromise the response to treatment, the patient's nutritional state, quality of life, and survival. In this article, we will approach key aspects in nutrition as well as the epidemiological characteristics and toxicities in patients affected by these pelvic tumors.


Assuntos
Gastroenteropatias/etiologia , Neoplasias Pélvicas/terapia , Qualidade de Vida , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Gastroenteropatias/fisiopatologia , Humanos , México/epidemiologia , Neoplasias Pélvicas/epidemiologia , Neoplasias Pélvicas/patologia , Prevalência , Lesões por Radiação/epidemiologia , Lesões por Radiação/fisiopatologia
13.
J Anim Ecol ; 84(2): 373-85, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25283305

RESUMO

Fragmentation per se due to human land conversion is a landscape-scale phenomenon. Accordingly, assessment of distributional patterns across a suite of potentially connected communities (i.e. metacommunity structure) is an appropriate approach for understanding the effects of landscape modification and complements the plethora of fragmentation studies that have focused on local community structure. To date, metacommunity structure within human-modified landscapes has been assessed with regard to nestedness along species richness gradients. This is problematic because there is little support that species richness gradients are associated with the factors moulding species distributions. More importantly, many alternative patterns are possible, and different patterns may manifest during different seasons and for different guilds because of variation in resource availability and resource requirements of taxa. We determined the best-fit metacommunity structure of a phyllostomid bat assemblage, frugivore ensemble, and gleaning animalivore ensemble within a human-modified landscape in the Caribbean lowlands of Costa Rica during the dry and wet seasons to elucidate important structuring mechanisms. Furthermore, we identified the landscape characteristics associated with the latent gradient underlying metacommunity structure. We discriminated among multiple metacommunity structures by assessing coherence, range turnover, and boundary clumping of an ordinated site-by-species matrix. We identified the landscape characteristics associated with the latent gradient underlying metacommunity structure via hierarchical partitioning. Metacommunity structure was never nested nor structured along a richness gradient. The phyllostomid assemblage and frugivore ensemble exhibited Gleasonian structure (range turnover along a common gradient) during the dry season and Clementsian structure (range turnover and shared boundaries along a common gradient) during the wet season. Distance between forest patches and forest edge density structured the phyllostomid metacommunity during the dry and wet seasons, respectively. Proportion of pasture and forest patch density structured the frugivore metacommunity during the dry season. Gleaning animalivores exhibited chequerboard structure (mutually exclusive species pairs) during the dry season and random structure during the wet season. Metacommunity structure was likely mediated by differential resource use or interspecific relationships. Furthermore, the interaction between landscape characteristics and seasonal variation in resources resulted in season-specific and guild-specific distributional patterns.


Assuntos
Quirópteros/fisiologia , Ecossistema , Estações do Ano , Animais , Costa Rica , Florestas , Herbivoria , Comportamento Predatório , Clima Tropical
14.
J Anim Ecol ; 83(5): 1124-36, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24428636

RESUMO

Research concerning spatial dynamics of biodiversity generally has been limited to considerations of the taxonomic dimension, which is insensitive to interspecific variation in ecological or evolutionary characteristics that play important roles in species assembly and provide linkages to ecosystem services. Consequently, the assumption that the taxonomic dimension is a good surrogate for other dimensions remains unconfirmed. We assessed variation in taxonomic (species richness) as well as phylogenetic and functional (Rao's quadratic entropy, a measurement of dispersion) dimensions of bat biodiversity along an elevational gradient in the Manu Biosphere Reserve of Peru. Phylogenetic dispersion was based on relatedness of species derived from a mammalian supertree. Functional dispersion was estimated separately for each of six functional components that reflect particular niche axes (e.g. diet, foraging strategy, body size) and for all functional components combined. Species richness declined nonlinearly with elevation, whereas phylogenetic dispersion and functional dispersion based on all functional components were not significantly associated with elevation (orthogonal polynomial regression). Moreover, considerable heterogeneity in the form of elevational relationships existed among functional components. After accounting for variation in species richness, dispersion of phylogenetic, diet and foraging strategy attributes were significantly greater than expected at high elevations, whereas dispersion of body size was significantly less than expected at high elevations. Species richness was a poor surrogate for phylogenetic or functional dispersion. Functional dispersion based on multiple components obscured patterns detected by particular components and hindered identification of mechanistic explanations for elevational variation in biodiversity. Variation in phylogenetic dispersion effectively captured the composite variation represented by all functional components, suggesting a phylogenetic signal in functional attributes. Mechanisms that give rise to variation in richness do not fully account for variation in phylogenetic or functional characteristics of assemblages. Greater than expected phylogenetic, diet and foraging strategy dispersion at high elevations were associated with the loss of phylogenetically or functionally redundant species, suggesting that increasing interspecific competition with decreasing productivity resulted in competitive exclusion. In contrast, low dispersion of size attributes at high elevations suggests the importance of abiotic filtering that favours small-sized species that can more easily enter torpor.


Assuntos
Altitude , Comportamento Apetitivo , Biodiversidade , Tamanho Corporal , Quirópteros/classificação , Quirópteros/fisiologia , Dieta , Filogenia , Animais , Evolução Biológica , Ecossistema , Geografia , Peru , Clima Tropical
15.
mSystems ; 9(6): e0042924, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38819150

RESUMO

In silico tools such as genome-scale metabolic models have shown to be powerful for metabolic engineering of microorganisms. Saccharomyces pastorianus is a complex aneuploid hybrid between the mesophilic Saccharomyces cerevisiae and the cold-tolerant Saccharomyces eubayanus. This species is of biotechnological importance because it is the primary yeast used in lager beer fermentation and is also a key model for studying the evolution of hybrid genomes, including expression pattern of ortholog genes, composition of protein complexes, and phenotypic plasticity. Here, we created the iSP_1513 GSMM for S. pastorianus CBS1513 to allow top-down computational approaches to predict the evolution of metabolic pathways and to aid strain optimization in production processes. The iSP_1513 comprises 4,062 reactions, 1,808 alleles, and 2,747 metabolites, and takes into account the functional redundancy in the gene-protein-reaction rule caused by the presence of orthologous genes. Moreover, a universal algorithm to constrain GSMM reactions using transcriptome data was developed as a python library and enabled the integration of temperature as parameter. Essentiality data sets, growth data on various carbohydrates and volatile metabolites secretion were used to validate the model and showed the potential of media engineering to improve specific flavor compounds. The iSP_1513 also highlighted the different contributions of the parental sub-genomes to the oxidative and non-oxidative parts of the pentose phosphate pathway. Overall, the iSP_1513 GSMM represent an important step toward understanding the metabolic capabilities, evolutionary trajectories, and adaptation potential of S. pastorianus in different industrial settings. IMPORTANCE: Genome-scale metabolic models (GSMM) have been successfully applied to predict cellular behavior and design cell factories in several model organisms, but no models to date are currently available for hybrid species due to their more complex genetics and general lack of molecular data. In this study, we generated a bespoke GSMM, iSP_1513, for this industrial aneuploid hybrid Saccharomyces pastorianus, which takes into account the aneuploidy and functional redundancy from orthologous parental alleles. This model will (i) help understand the metabolic capabilities and adaptive potential of S. pastorianus (domestication processes), (ii) aid top-down predictions for strain development (industrial biotechnology), and (iii) allow predictions of evolutionary trajectories of metabolic pathways in aneuploid hybrids (evolutionary genetics).


Assuntos
Genoma Fúngico , Redes e Vias Metabólicas , Saccharomyces , Saccharomyces/genética , Saccharomyces/metabolismo , Redes e Vias Metabólicas/genética , Genoma Fúngico/genética , Modelos Biológicos , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Evolução Molecular , Microbiologia Industrial/métodos
16.
Heliyon ; 10(1): e23629, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192840

RESUMO

Background: Pediatric COVID-19 patients have lower rates of hospitalization and fatal outcomes compared to adults with COVID-19; however, children represent a challenge in the detection, diagnosis, and treatment of COVID-19. Our aim was to determine the risk factors for hospital admission, invasive mechanical ventilation, and mortality in pediatric COVID-19 patients in Mexico during the COVID-19 pandemic. Material and methods: A retrospective cohort of pediatric patients with COVID-19 from February 2020 to April 2021 was reported on the National Epidemiological Surveillance System for Viral Respiratory Disease (SISVER) platform. Results: Among the 104,133 patients included in our study, 6214 were hospitalized, and 621 patients underwent invasive mechanical ventilation. A total of 0.65 % died during hospitalization. Children aged <12 months (odds ratio [OR]: 17.1; 95 % confidence interval [CI]: 15.9-19.4, p < 0.001), 1-4 years (OR: 3.69; 95 % CI: 3.2-4.1, p < 0.001), 5-9 years (OR: 1.86; 95 % CI: 1.66-2.08, p < 0.001), and 10-14 years (OR: 1.23; 95 % CI: 1.11-1.37, p < 0.001), and those diagnosed with diabetes (OR: 2.32; 95 % CI 1.68-3.20, p < 0.001) and obesity (OR: 1.24; 95 % CI 1.04-1.48, p = 0.015) were associated with hospital admission. Renal disease (OR: 3.85; 95 % CI: 2.25-6.59, p < 0.001) was associated with invasive mechanical ventilation. Pneumonia (OR: 15.9; 95 % CI: 12.6-20.1, p < 0.001) and renal disease (OR: 3.85; 95 % CI: 2.25-6.59, p value < 0.001) were associated with death. Conclusion: Pneumonia increases the risk of death. The youngest age group has a higher risk of hospital admission. Comorbidities such as renal disease or immunosuppression increase the risk of death in all age groups.

17.
Curr Probl Cancer ; 48: 101041, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37988902

RESUMO

BACKGROUND: Cervical cancer (CC) in Mexico is diagnosed mainly in locally advanced (LACC) and advanced (ACC) stages, where ureteral obstruction is more frequent. The standard treatment for this population is concurrent chemoradiotherapy (CCRT) with cisplatin, which is nephrotoxic and could lead to further deterioration of renal function in LACC patients with renal function decline. We aimed to evaluate the effect of CCRT with Gemcitabine on renal function in LACC patients. METHODS: This retrospective study included LACC patients treated with CCRT with Gemcitabine as a radiosensitizer from February 2003 to December 2018. Data were collected from medical archives and electronic records. We assessed renal function before and after CCRT treatment and analyzed the patient's response to treatment and survival. RESULTS: 351 LACC patients treated were included and stratified into two groups: 198 with Glomerular Filtration Rate (GFR) ≥60ml/min (group A) and 153 with GFR<60ml/min (group B). An improvement in GFR was observed after CCRT in patients in group B, from 33 ml/min to 57.5 ml/min (p<0.001). Complete response was observed in 64.1% of patients in Group A and 43.8% in Group B (p<0.0001). Factors associated with increased risk of death included having a GFR of 15-29 ml/min (HR: 2.17; 1.08-4.35), having GFR<15 ml/min (HR: 3.08; 1.63-5.79), and receiving Boost treatment (HR: 2.09; 1.18-3.69). On the other hand, receiving brachytherapy is a positive predictor for OS (HR:0.51; 0.31-0.84). CONCLUSION: CCRT with gemcitabine is an appropriate treatment option for patients diagnosed with LACC who present impaired renal function due to the disease's obstructive nature or other comorbidities.


Assuntos
Nefropatias , Neoplasias do Colo do Útero , Feminino , Humanos , Gencitabina , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/terapia , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Rim
18.
Commun Biol ; 6(1): 918, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679437

RESUMO

Kazachstania bulderi is a non-conventional yeast species able to grow efficiently on glucose and δ-gluconolactone at low pH. These unique traits make K. bulderi an ideal candidate for use in sustainable biotechnology processes including low pH fermentations and the production of green chemicals including organic acids. To accelerate strain development with this species, detailed information of its genetics is needed. Here, by employing long read sequencing we report a high-quality phased genome assembly for three strains of K. bulderi species, including the type strain. The sequences were assembled into 12 chromosomes with a total length of 14 Mb, and the genome was fully annotated at structural and functional levels, including allelic and structural variants, ribosomal array and mating type locus. This high-quality reference genome provides a resource to advance our fundamental knowledge of biotechnologically relevant non-conventional yeasts and to support the development of genetic tools for manipulating such strains towards their use as production hosts in biotechnological processes.


Assuntos
Saccharomycetales , Saccharomycetales/genética , Alelos , Biotecnologia , Concentração de Íons de Hidrogênio
19.
Sci Rep ; 12(1): 1216, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-35075255

RESUMO

Chronic Obstructive Pulmonary Disease (COPD) patients have alterations in body composition. Bioelectrical impedance analysis (BIA) evaluates body composition, hydration status, and fluid distribution. Subjects with fluid disturbances have been found to have lower FEV1, respiratory muscle strength, and poor prognosis. We aimed to evaluate the effect of hydration status and fluid distribution on pulmonary function in COPD patients. A cross-sectional study, 180 patients with a confirmed diagnosis of COPD were included. Patients with asthma, advanced renal or liver disease, acute HF, exacerbation of COPD, or pacemakers were excluded. Hydration status variables (TBW, ECW, ICW) and disturbance of fluid distribution [impedance ratio (IR) > 0.84 and phase angle (PhA)] were evaluated by BIA. Pulmonary function was assessed by spirometry. The mean population age was 71.55 ± 8.94 years; 55% were men. Subjects were divided into two groups according to the IR ≥ 0.84 or < 0.84. The group with higher IR ≥ 0.84 had lower FEV1, FVC, FEV1/FVC, DLCO and, PhA compared to those with IR < 0.84. After adjusting for confounding variables TBW, ECW, IR ≥ 0.84, PhA, and resistance/height increase were associated with decreased FEV1. In the same way, with IR ≥ 0.84, edema index ≥ 0.48, trunk and abdominal IR were negatively associated with FVC, and PhA had a positive association with FVC. Fluid distribution, especially IR and PhA, could be a useful parameter for predicting pulmonary function in COPD patients.


Assuntos
Pulmão/fisiopatologia , Estado de Hidratação do Organismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Estudos Transversais , Impedância Elétrica , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Capacidade Vital
20.
Rev Invest Clin ; 63 Suppl 1: 73-8, 2011 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-22916615

RESUMO

BACKGROUND: Liver transplantation is the only curative alternative for patients with end stage liver disease or acute liver failure. AIM: To report the experience of a single transplant center in Mexico. MATERIAL AND METHODS: Fifty-five transplants in 54 adult patients were analyzed between 1999 and 2011 in a single private institution. All grafts were obtained from deceased donor. Surgical technique, donor and recipient demographics, complications, causes of death and overall survival are described. Results were expressed as range and percentages. A Kaplan-Meier survival curve was done to analyze patient and graft survival. RESULTS: Main cause of cirrhosis was hepatitis C virus infection followed by alcohol intake. A 16% of patients developed biliary complications without graft loss, and vascular complications were observed in 15%. Patient survival at one and five years was 83% and 76%, respectively. CONCLUSIONS: Complication rates and survival in our center are comparable to those in the United States and Europe.


Assuntos
Transplante de Fígado/estatística & dados numéricos , Adolescente , Adulto , Hospitais , Humanos , Transplante de Fígado/efeitos adversos , México , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Adulto Jovem
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