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Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding for the ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The management of CF disease has evolved in recent decades from treating downstream disease manifestations affecting the airways, the lungs and the gastrointestinal system to addressing the CFTR gene defect. The advent of CFTR modulators, which correct the functionality of the defective CFTR, contributes to reshaping the landscape of CF demographics, prognosis and therapies, including nutritional management. A spectrum of clinical manifestations is emerging within the same patient population where undernutrition and nutritional deficiencies coexist with excessive weight gain and metabolic derangements. Such contrasting presentations challenge current practices, require adjustments to traditional approaches, and involve more individualised interventions. This narrative review examines the current state of knowledge on the nutritional management of people living with cystic fibrosis from early life to adulthood in the era of CFTR modulation.
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Fibrose Cística , Humanos , Fibrose Cística/complicações , Fibrose Cística/genética , Fibrose Cística/terapia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Prognóstico , Pulmão , Medicina de PrecisãoRESUMO
BACKGROUND: Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. METHOD: A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016-2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. RESULTS: Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%-27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%-9.2%), 13.7% (95% CI: 9.9%-18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%-5.5%) for symptomatic influenza. CONCLUSIONS: Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. CLINICAL TRIALS REGISTRATION: NCT02868658.
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Vacinas contra Influenza , Influenza Humana , Pessoal de Saúde , Humanos , Incidência , Controle de Infecções , Influenza Humana/epidemiologia , Estudos Prospectivos , VacinaçãoRESUMO
Basal stem rot caused by Ganoderma boninense is the major threat to oil palm cultivation in Southeast Asia, which accounts for 80% of palm oil production worldwide, and this disease is increasing in Africa. The use of resistant planting material as part of an integrated pest management of this disease is one sustainable solution. However, breeding for Ganoderma resistance requires long-term and costly research, which could greatly benefit from marker-assisted selection (MAS). In this study, we evaluated the effectiveness of an in silico genetic mapping approach that took advantage of extensive data recorded in an ongoing breeding program. A pedigree-based QTL mapping approach applied to more than 10 years' worth of data collected during pre-nursery tests revealed the quantitative nature of Ganoderma resistance and identified underlying loci segregating in genetic diversity that is directly relevant for the breeding program supporting the study. To assess the consistency of QTL effects between pre-nursery and field environments, information was collected on the disease status of the genitors planted in genealogical gardens and modeled with pre-nursery-based QTL genotypes. In the field, individuals were less likely to be infected with Ganoderma when they carried more favorable alleles at the pre-nursery QTL. Our results pave the way for a MAS of Ganoderma resistant and high yielding planting material, and the provided proof-of-concept of this efficient and cost-effective approach could motivate similar studies based on diverse breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01246-9.
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BACKGROUND AND AIMS: Deterioration of anthropometric and lung function parameters was shown to precede the onset of cystic fibrosis-related diabetes (CFRD) in adults. In children, studies have been conducted in small cohorts with relatively short observation period. Study objectives were to document the longitudinal trends of anthropometric, pulmonary, nutritional and metabolic parameters from cystic fibrosis (CF) diagnosis to the ascertainment of abnormal glucose tolerance and identify parameters associated with the incidence of such abnormalities in a pediatric CF cohort. METHODS AND RESULTS: Retrospective cohort study of 281 children with CF. Longitudinal trends of anthropometric, lung function, nutritional and metabolic data were generated from CF diagnosis to the ascertainment of abnormal glucose tolerance defined as the presence of either impaired glucose tolerance (IGT), unconfirmed CFRD or CFRD. Cox models and Kaplan-Meier curves were used to identify factors associated with developing abnormal glucose tolerance. Forty-five percent of cohort had normal glucose tolerance (NGT), 27% IGT, 10% unconfirmed CFRD and 18% CFRD. Children who developed CFRD displayed lower height z-scores from a very early age. Conversely, HbA1c levels began to rise closer to CFRD ascertainment. Height z-scores (HR: 0.45; CI 95% [0.29-0.69]) and HbA1c (HR: 2.43; CI 95% [1.86-3.18]) in years preceding ascertainment were associated with the risk of developing CFRD. CONCLUSION: Children who developed CFRD display distinctive trends for height z-scores from a very early age, whereas HbA1c appears as a marker of established glucose metabolism derangements.
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Glicemia/metabolismo , Fibrose Cística/complicações , Intolerância à Glucose/etiologia , Adolescente , Fatores Etários , Biomarcadores/sangue , Criança , Fibrose Cística/diagnóstico , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
Wood production in fast-growing Eucalyptus grandis trees is highly dependent on both potassium (K) fertilization and water availability but the molecular processes underlying wood formation in response to the combined effects of these two limiting factors remain unknown. E. grandis trees were submitted to four combinations of K-fertilization and water supply. Weighted gene co-expression network analysis and MixOmics-based co-regulation networks were used to integrate xylem transcriptome, metabolome and complex wood traits. Functional characterization of a candidate gene was performed in transgenic E. grandis hairy roots. This integrated network-based approach enabled us to identify meaningful biological processes and regulators impacted by K-fertilization and/or water limitation. It revealed that modules of co-regulated genes and metabolites strongly correlated to wood complex traits are in the heart of a complex trade-off between biomass production and stress responses. Nested in these modules, potential new cell-wall regulators were identified, as further confirmed by the functional characterization of EgMYB137. These findings provide new insights into the regulatory mechanisms of wood formation under stressful conditions, pointing out both known and new regulators co-opted by K-fertilization and/or water limitation that may potentially promote adaptive wood traits.
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Eucalyptus/crescimento & desenvolvimento , Potássio/farmacologia , Biologia de Sistemas , Árvores/crescimento & desenvolvimento , Água/farmacologia , Madeira/crescimento & desenvolvimento , Biomassa , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Eucalyptus/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Fenótipo , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Árvores/efeitos dos fármacos , Madeira/efeitos dos fármacos , Xilema/efeitos dos fármacos , Xilema/genética , Xilema/crescimento & desenvolvimentoRESUMO
Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.
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Acromegalia , Consenso , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Estudos Prospectivos , Estudos Retrospectivos , SomatostatinaRESUMO
Introduction: Lipomas are the most common benign mesenchymal tumors which can be found in any part of the body. Nevertheless, their etiology and pathogenesis remain unknown. It is hypothesized that some of these lesions could result from an acute or chronic trauma. Patients and methods: We report a case of a 54-year-old man presenting a perineal lipoma which volume grew rapidly after he fell on his buttock, in the context of inaugural epileptic seizure. Pelvic MRI showed a voluminous fatty mass, measuring 6.6 × 5 × 9 cm without any signs of local invasion. Furthermore, we review the latest research on lipomas originating from traumatic lesion. Results: The mass was completely excised in one block under general anesthaesia, using an elliptical incision and a deep dissection. We did not close the skin incision in view of the cutaneous defect. Post-operative recovery was uneventful and the patient was discharged from hospital two days after the operation. Histopathology indicated a reorganised lipoma with no evidence of malignancy. Conclusion: Perineal lipomas are extremely rare, pathological examination of imaging guided biopsies are needed to exclude malignancy especially a well-differentiated liposarcoma. MRI remains the first option and radical surgical excision is the gold standard treatment.
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Neoplasias do Ânus/etiologia , Lipoma/etiologia , Neoplasias Pélvicas/etiologia , Períneo/lesões , Lesões dos Tecidos Moles/complicações , Acidentes por Quedas , Neoplasias do Ânus/cirurgia , Humanos , Lipoma/diagnóstico por imagem , Lipoma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/cirurgia , Períneo/diagnóstico por imagem , Períneo/cirurgia , Convulsões/complicaçõesRESUMO
PURPOSE: To compare the diagnostic accuracy of DWI and STIR sequences in Whole body (WB) MRI of SpA patients. MATERIALS AND METHODS: Twenty consecutive patients with confirmed active SpA and 20 controls were investigated with identical WB MRI protocols, including DWI and STIR images. Two observers recorded 'lesions' (high signal intensity foci on STIR and high b-value DWI) in 17 anatomical areas, making a 17-point 'area score' and a 40-point 'lesion score'. ROC performance, inter-observer agreement, correlation with clinical parameters and spine and sacro-iliac joints (SIJ) MRI scores were assessed. RESULTS: SpA patients had significantly higher lesion scores on DWI than on STIR (p<0.025). The lesion score area under the curve was significantly higher with DWI (99.9) than with STIR (95.8, p=0.02). DWI lesion score ≥5 had both sensitivity and specificity ≥85 %. With STIR the best threshold ≥3 yielded sensitivity ≥85 % and specificity ≥60 %. DWI area score ≥3 yielded sensitivity ≥85 % and specificity ≥80 %. With STIR the best threshold ≥4 yielded sensitivity ≥70 % and specificity ≥80 %. Inter-observer agreement was strong for both sequences. In patients, the lesion score was positively correlated with ASDAS-CRP, log(CRP), and local MRI scores. CONCLUSIONS: DWI is a promising alternative to STIR in WB MRI to detect active SpA lesions. KEY POINTS: ⢠DWI is a robust alternative to STIR in WBMRI in SpA. ⢠DWI might be superior in discriminating relevant inflammatory and degenerative changes. ⢠Positive correlations exist between WB MRI, clinical, biological, local MRI data. ⢠Distribution and frequency of abnormal MRI findings in SpA are highlighted.
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Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Espondilartrite/diagnóstico por imagem , Imagem Corporal Total/métodos , Adulto , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Articulação Sacroilíaca/diagnóstico por imagem , Articulação Sacroilíaca/patologia , Sensibilidade e Especificidade , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Adulto JovemRESUMO
MOTIVATION: Advances in high-throughput technologies have led to the acquisition of various types of -omic data on the same biological samples. Each data type gives independent and complementary information that can explain the biological mechanisms of interest. While several studies performing independent analyses of each dataset have led to significant results, a better understanding of complex biological mechanisms requires an integrative analysis of different sources of data. RESULTS: Flexible modeling approaches, based on penalized likelihood methods and expectation-maximization (EM) algorithms, are studied and tested under various biological relationship scenarios between the different molecular features and their effects on a clinical outcome. The models are applied to genomic datasets from two cancer types in the Cancer Genome Atlas project: glioblastoma multiforme and ovarian serous cystadenocarcinoma. The integrative models lead to improved model fit and predictive performance. They also provide a better understanding of the biological mechanisms underlying patients' survival. AVAILABILITY AND IMPLEMENTATION: Source code implementing the integrative models is freely available at https://github.com/mgt000/IntegrativeAnalysis along with example datasets and sample R script applying the models to these data. The TCGA datasets used for analysis are publicly available at https://tcga-data.nci.nih.gov/tcga/tcgaDownload.jsp CONTACT: marie.denis@cirad.fr or mgt26@georgetown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Genômica , Algoritmos , Genoma , Glioblastoma , Humanos , Funções VerossimilhançaRESUMO
Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.
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Anti-Inflamatórios/administração & dosagem , Frutas/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Malus/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Ciclo-Oxigenase 2/metabolismo , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse OxidativoAssuntos
Abscesso , Fístula , Abscesso/etiologia , Abscesso/cirurgia , Drenagem , Eletrocoagulação , Endossonografia , Humanos , Stents , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: To study the potential of genomic selection for heterosis resulting from multiplicative interactions between additive and antagonistic components, we focused on oil palm, where bunch production is the product of bunch weight and bunch number. We simulated two realistic breeding populations and compared current reciprocal recurrent selection (RRS) with reciprocal recurrent genomic selection (RRGS) over four generations. All breeding strategies aimed at selecting the best individuals in parental populations to increase bunch production in hybrids. For RRGS, we obtained the parental genomic estimated breeding values using GBLUP with hybrid phenotypes as data records and population specific allele models. We studied the effects of four RRGS parameters on selection response and genetic parameters: (1) the molecular data used to calibrate the GS model: in RRGS_PAR, we used parental genotypes and in RRGS_HYB we also used hybrid genotypes; (2) frequency of progeny tests (model calibration); (3) number of candidates and (4) number of genotyped hybrids in RRGS_HYB. RESULTS: We concluded that RRGS could increase the annual selection response compared to RRS by decreasing the generation interval and by increasing the selection intensity. With 1700 genotyped hybrids, calibration every four generations and 300 candidates per generation and population, selection response of RRGS_HYB was 71.8 % higher than RRS. RRGS_PAR with calibration every two generations and 300 candidates was a relevant alternative, as a good compromise between the annual response, risk around the expected response, increased inbreeding and cost. RRGS required inbreeding management because of a higher annual increase in inbreeding than RRS. CONCLUSIONS: RRGS appeared as a valuable method to achieve a long-term increase in the performance for a trait showing heterosis due to the multiplicative interaction between additive and negatively correlated components, such as oil palm bunch production.
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Arecaceae/genética , Genômica/métodos , Vigor Híbrido/genética , Óleos de Plantas/metabolismo , Locos de Características Quantitativas/genética , Simulação por Computador , Genótipo , Hibridização Genética , Endogamia , Óleo de Palmeira , Seleção Genética , Fatores de TempoRESUMO
BACKGROUND: Elaeis guineensis is the world's leading source of vegetable oil, and the demand is still increasing. Oil palm breeding would benefit from marker-assisted selection but genetic studies are scarce and inconclusive. This study aims to identify genetic bases of oil palm production using a pedigree-based approach that is innovative in plant genetics. RESULTS: A quantitative trait locus (QTL) mapping approach involving two-step variance component analysis was employed using phenotypic data on 30852 palms from crosses between more than 300 genotyped parents of two heterotic groups. Genome scans were performed at parental level by modeling QTL effects as random terms in linear mixed models with identity-by-descent (IBD) kinship matrices. Eighteen QTL regions controlling production traits were identified among a large genetically diversified sample from breeding program. QTL patterns depended on the genetic origin, with only one region shared between heterotic groups. Contrasting effects of QTLs on bunch number and weights reflected the close negative correlation between the two traits. CONCLUSIONS: The pedigree-based approach using data from ongoing breeding programs is a powerful, relevant and economic approach to map QTLs. Genetic determinisms contributing to heterotic effects have been identified and provide valuable information for orienting oil palm breeding strategies.
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Arecaceae/genética , Ligação Genética , Repetições de Microssatélites/genética , Locos de Características Quantitativas/genética , Cruzamento , Mapeamento Cromossômico , Cruzamentos Genéticos , Genótipo , Modelos Genéticos , Óleo de Palmeira , Linhagem , Óleos de PlantasRESUMO
Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.
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Antioxidantes/química , Inflamação/tratamento farmacológico , Intestinos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Vaccinium macrocarpon/química , Trifosfato de Adenosina/metabolismo , Apoptose , Biflavonoides/química , Células CACO-2 , Catequina/química , Dinoprostona/metabolismo , Ácidos Graxos/química , Humanos , Peroxidação de Lipídeos , Fosforilação Oxidativa , Proantocianidinas/químicaRESUMO
KEY MESSAGE: Genomic selection empirically appeared valuable for reciprocal recurrent selection in oil palm as it could account for family effects and Mendelian sampling terms, despite small populations and low marker density. Genomic selection (GS) can increase the genetic gain in plants. In perennial crops, this is expected mainly through shortened breeding cycles and increased selection intensity, which requires sufficient GS accuracy in selection candidates, despite often small training populations. Our objective was to obtain the first empirical estimate of GS accuracy in oil palm (Elaeis guineensis), the major world oil crop. We used two parental populations involved in conventional reciprocal recurrent selection (Deli and Group B) with 131 individuals each, genotyped with 265 SSR. We estimated within-population GS accuracies when predicting breeding values of non-progeny-tested individuals for eight yield traits. We used three methods to sample training sets and five statistical methods to estimate genomic breeding values. The results showed that GS could account for family effects and Mendelian sampling terms in Group B but only for family effects in Deli. Presumably, this difference between populations originated from their contrasting breeding history. The GS accuracy ranged from -0.41 to 0.94 and was positively correlated with the relationship between training and test sets. Training sets optimized with the so-called CDmean criterion gave the highest accuracies, ranging from 0.49 (pulp to fruit ratio in Group B) to 0.94 (fruit weight in Group B). The statistical methods did not affect the accuracy. Finally, Group B could be preselected for progeny tests by applying GS to key yield traits, therefore increasing the selection intensity. Our results should be valuable for breeding programs with small populations, long breeding cycles, or reduced effective size.
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Arecaceae/genética , Cruzamento , Seleção Genética , Genética Populacional , Genótipo , Repetições de Microssatélites , Modelos Genéticos , Modelos EstatísticosRESUMO
KEY MESSAGE: Explicit pedigree reconstruction by simulated annealing gave reliable estimates of genealogical coancestry in plant species, especially when selfing rate was lower than 0.6, using a realistic number of markers. Genealogical coancestry information is crucial in plant breeding to estimate genetic parameters and breeding values. The approach of Fernández and Toro (Mol Ecol 15:1657-1667, 2006) to estimate genealogical coancestries from molecular data through pedigree reconstruction was limited to species with separate sexes. In this study it was extended to plants, allowing hermaphroditism and monoecy, with possible selfing. Moreover, some improvements were made to take previous knowledge on the population demographic history into account. The new method was validated using simulated and real datasets. Simulations showed that accuracy of estimates was high with 30 microsatellites, with the best results obtained for selfing rates below 0.6. In these conditions, the root mean square error (RMSE) between the true and estimated genealogical coancestry was small (<0.07), although the number of ancestors was overestimated and the selfing rate could be biased. Simulations also showed that linkage disequilibrium between markers and departure from the Hardy-Weinberg equilibrium in the founder population did not affect the efficiency of the method. Real oil palm data confirmed the simulation results, with a high correlation between the true and estimated genealogical coancestry (>0.9) and a low RMSE (<0.08) using 38 markers. The method was applied to the Deli oil palm population for which pedigree data were scarce. The estimated genealogical coancestries were highly correlated (>0.9) with the molecular coancestries using 100 markers. Reconstructed pedigrees were used to estimate effective population sizes. In conclusion, this method gave reliable genealogical coancestry estimates. The strategy was implemented in the software MOLCOANC 3.0.
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Algoritmos , Arecaceae/genética , Cruzamento , Linhagem , Filogenia , Óleos de Plantas/metabolismo , Simulação por Computador , Marcadores Genéticos , Genética Populacional , Desequilíbrio de Ligação/genética , Repetições de Microssatélites/genética , Óleo de Palmeira , Autofertilização/genéticaRESUMO
The nonreceptor Syk kinase is detected in epithelial cells, where it acts as a tumor suppressor, in addition to its well-established role in immunoreceptor-based signal transduction in hematopoietic cells. Thus, several carcinomas and melanomas have subnormal concentrations of Syk. Although Syk is mainly localized at the plasma membrane, it is also present in centrosomes, where it is involved in the control of cell division. The mechanisms responsible for its centrosomal localization and action are unknown. We used wild-type and mutant fluorescent Syk fusion proteins in live-cell imaging (fluorescence recovery after photobleaching, total internal reflection fluorescence, and photoactivation) combined with mathematical modeling to demonstrate that Syk is actively transported to the centrosomes via the microtubules and that this transport depends on the dynein/dynactin molecular motor. Syk can only target the centrosomes if its kinase activity is intact and it is catalytically active at the centrosomes. We showed that the autophosphorylated Y130 Syk residue helps to uncouple Syk from the plasma membrane and to promote its translocation to the centrosome, suggesting that the subcellular location of Syk depends on its autophosphorylation on specific tyrosine residues. We have thus established the details of how Syk is trafficked intracellularly and found evidence that its targeting to the centrosomes is controlled by autophosphorylation.
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Centrossomo/metabolismo , Dineínas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Microtúbulos/microbiologia , Proteínas Tirosina Quinases/metabolismo , Animais , Biocatálise , Western Blotting , Linhagem Celular , Humanos , Transdução de Sinais , Frações Subcelulares/metabolismo , Quinase SykRESUMO
Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Humanos , Vulnerabilidade Social , Recidiva Local de Neoplasia , Sociedades Médicas , Linfócitos TRESUMO
BACKGROUND: Immunosuppressive drugs may prevent or partially reverse progression of renal AA-amyloidosis, a rare complication of Crohn's disease, often fatal due to renal failure. MATERIALS AND METHODS: The clinical, biological and pathological data of 16 patients treated since 1976 were reviewed. Serum amyloid A was determined in surviving patients. RESULTS: The median age of the 16 patients (13 men) was 23·5 years (range 16-69). At Crohn's disease onset, Montreal phenotypes were similar to reported data. Out of 15 patients with renal insufficiency, 8 developed a nephrotic syndrome and 7 a low grade proteinuria. The single patient without renal insufficiency had nephrotic syndrome. A significant correlation (P < 0·05) between the extension of renal amyloid A and sclerosis was found in 12 patients. One patient had a 10 year remission of nephrotic syndrome with immunosuppressive drugs. In 6 patients treated with anti-TNF-α (Tumor-Necrosis-Factor-α) agents, anaphylactic reaction (1/6), death from septic shock (1/6), 5-year remission (1/6) or reduction of nephrotic syndrome (1/6) and stabilization of renal insufficiency (2/6) were observed. Surgery was performed in 10 patients. Kidney transplantation was performed in 5 of the 8 patients dialysed for end-stage renal failure. Among 6/16 patients (37%) still alive, 3 belong to the 5 transplanted patients (survival: 3-20 years) and 3 to the anti-TNF-α drugs treated patients; all but one exhibited a low serum amyloid A level. CONCLUSIONS: Suppression of Crohn's disease inflammation potentially leads to the control of amyloid A production, assessed by a decrease of serum amyloid A. Kidney transplantation provides a long survival.