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2.
Invest Ophthalmol Vis Sci ; 63(1): 12, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34994768

RESUMO

Purpose: The purpose of this study was to investigate the perimetric features and their associations with structural and functional features in patients with RP1L1-associated occult macular dystrophy (OMD; i.e. Miyake disease). Methods: In this international, multicenter, retrospective cohort study, 76 eyes of 38 patients from an East Asian cohort of patients with RP1L1-associated OMD were recruited. Visual field tests were performed using standard automated perimetry, and the patients were classified into three perimetric groups based on the visual field findings: central scotoma, other scotoma (e.g. paracentral scotoma), and no scotoma. The association of the structural and functional findings with the perimetric findings was evaluated. Results: Fifty-four eyes (71.1%) showed central scotoma, 14 (18.4%) had other scotomata, and 8 (10.5%) had no scotoma. Central scotoma was mostly noted in both eyes (96.3%) and within the central 10 degrees (90.7%). Among the three perimetric groups, there were significant differences in visual symptoms, best-corrected visual acuity (BCVA), and structural phenotypes (i.e. severity of photoreceptor changes). The central scotoma group showed worse BCVA often with severe structural abnormalities (96.3%) and a pathogenic variant of p.R45W (72.2%). The multifocal electroretinogram (mfERG) groups largely corresponded with the perimetric groups; however, 8 (10.5%) of 76 eyes showed mfERG abnormalities preceding typical central scotoma. Conclusions: The patterns of scotoma with different clinical severity were first identified in occult macular dystrophy, and central scotoma, a severe pattern, was most frequently observed. These perimetric patterns were associated with the severity of BCVA, structural phenotypes, genotype, and objective functional characteristics which may precede in some cases.


Assuntos
Degeneração Macular/fisiopatologia , Escotoma/fisiopatologia , Campos Visuais/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrorretinografia , Proteínas do Olho/genética , Extremo Oriente , Feminino , Genótipo , Humanos , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Escotoma/diagnóstico por imagem , Escotoma/genética , Tomografia de Coerência Óptica , Acuidade Visual/fisiologia , Testes de Campo Visual , Adulto Jovem
3.
An Acad Bras Cienc ; 94(1): e20191559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35018998

RESUMO

The aim was to evaluate the association between growth, carcass and visual scores traits with precocious calving in Nellore cattle. Birth weight (BW), weight at 120, 210, 365 and 450 days of age, pre and post-weaning average daily gain, rib eye area, backfat thickness (BF), rump fat thickness and visual scores obtained at 18 months were used for the analysis. Records from 700 females born between 2009 and 2015, exposed to mating starting at 11 months of age were analyzed. Discriminant analyzes were performed with the software Statistica. BW and BF showed the highest (P>0.01) discrimination value for early heifer pregnancy (EP). Extreme intrauterine growth retardation can result in slower growth, which reflects in the worst reproductive performance, confirmed by the variation in BW between precocious and conventional heifers. The results also demonstrate that the level of body fat affects begin of puberty. Bone structure, musculature, depth, tail insertion and rump scores presented the highest discrimination value for EP. These traits can be used as selection tools to improve sexual precocity in female Nellore cattle. The results obtained in this study would support farmers to guide the heifer management and decisions in order to enhance the EP.


Assuntos
Tecido Adiposo , Reprodução , Animais , Bovinos , Feminino , Fenótipo , Gravidez , Desmame
4.
World J Microbiol Biotechnol ; 38(3): 41, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018552

RESUMO

The most crucial and expensive fragment in the broiler chicken production industry is the feed. Because of the rising demand, finding a cheap and effective feed is an urgent necessity. Fermentation of broiler feed by probiotic fungal starters can enhance the nutrient's availability and digestibility while preventing pathogenic growth. In this study different Rhizopus spp. have been isolated from agricultural soils around Izmir, Turkey, and tested for their probiotic potential and fermentative capacity. The isolated Rhizopus strains first underwent microscopical fluorescent investigation to exclude endofungal bacterial presence, then, those without endofungal bacteria (totally 82) were tested for antimicrobial activity counter bacterial and fungal pathogens. The ones with wide-spectrum antimicrobial activity (totally 10) were tested for gastrointestinal tolerance and antioxidant ability. Upon phenotypic and genotypic identification, the 10 isolates were found to belong to Rhizopus oryzae species. While all 10 strains showed variable gastrointestinal tolerance and antioxidant activities, three of them (92/1, 236/2, and 284) had relatively high antioxidant activity. Upon fermentative capacity assay, compared to unfermented commercial feed, there was a general decrease in crude fiber content by 56% after fermentation by 92/1 isolate for 4 days and 236/2 isolate for 2 days. The highest increase in crude protein content (by 14.5%) occurred after a 4-day fermentation period by 236/2 isolate. The highest increase in metabolizable energy was 8.64%, by the 284 isolate after 2 days of fermentation. In conclusion, the three strains showed good probiotic properties and fermentative capacities hence can be beneficial for the poultry industry.


Assuntos
Ração Animal , Produtos Agrícolas/microbiologia , Fermentação , Probióticos , Rhizopus oryzae/metabolismo , Animais , Antibacterianos , Antifúngicos , Antioxidantes/metabolismo , Galinhas , Genótipo , Fenótipo , Rhizopus oryzae/genética , Rhizopus oryzae/isolamento & purificação , Solo , Microbiologia do Solo
5.
BMC Genomics ; 23(1): 26, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991478

RESUMO

BACKGROUND: Valgus-varus deformity (VVD) is a lateral or middle deviation of the tibiotarsus or tarsometatarsus, which is associated with compromised growth, worse bone quality and abnormal changes in serum indicators in broilers. To investigate the genetic basis of VVD, a genome wide association study (GWAS) was performed to identify candidate genes and pathways that are responsible for VVD leg disease, serum indicators and growth performance in broilers. RESULTS: In total, VVD phenotype, seven serum indicators and three growth traits were measured for 126 VVD broilers (case group) and 122 sound broilers (control group) based on a high throughput genome wide genotyping-by-sequencing (GBS) method. After quality control 233 samples (113 sound broilers and 120 VVD birds) and 256,599 single nucleotide polymorphisms (SNPs) markers were used for further analysis. As a result, a total of 5 SNPs were detected suggestively significantly associated with VVD and 70 candidate genes were identified that included or adjacent to these significant SNPs. In addition, 43 SNPs located on Chr24 (0.22 Mb - 1.79 Mb) were genome-wide significantly associated with serum alkaline phosphatase (ALP) and 38 candidate genes were identified. Functional enrichment analysis showed that these genes are involved in two Gene Ontology (GO) terms related to bone development (cartilage development and cartilage condensation) and two pathways related to skeletal development (Toll-like receptor signaling pathway and p53 signaling pathway). BARX2 (BARX homeobox 2) and Panx3 (Pannexin 3) related to skeleton diseases and bone quality were obtained according to functional analysis. According to the integration of GWAS with transcriptome analysis, HYLS1 (HYLS1 centriolar and ciliogenesis associated) was an important susceptibility gene. CONCLUSIONS: The results provide some reference for understanding the relationship between metabolic mechanism of ALP and pathogenesis of VVD, which will provide a theoretical basis for disease-resistant breeding of chicken leg soundness.


Assuntos
Galinhas , Estudo de Associação Genômica Ampla , Animais , Galinhas/genética , Perfilação da Expressão Gênica , Fenótipo , Polimorfismo de Nucleotídeo Único
6.
Genet Sel Evol ; 54(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979897

RESUMO

BACKGROUND: The genetic background of trait variability has captured the interest of ecologists and animal breeders because the genes that control it could be involved in buffering various environmental effects. Phenotypic variability of a given trait can be assessed by studying the heterogeneity of the residual variance, and the quantitative trait loci (QTL) that are involved in the control of this variability are described as variance QTL (vQTL). This study focuses on litter size (total number born, TNB) and its variability in a Large White pig population. The variability of TNB was evaluated either using a simple method, i.e. analysis of the log-transformed variance of residuals (LnVar), or the more complex double hierarchical generalized linear model (DHGLM). We also performed a single-SNP (single nucleotide polymorphism) genome-wide association study (GWAS). To our knowledge, this is only the second study that reports vQTL for litter size in pigs and the first one that shows GWAS results when using two methods to evaluate variability of TNB: LnVar and DHGLM. RESULTS: Based on LnVar, three candidate vQTL regions were detected, on Sus scrofa chromosomes (SSC) 1, 7, and 18, which comprised 18 SNPs. Based on the DHGLM, three candidate vQTL regions were detected, i.e. two on SSC7 and one on SSC11, which comprised 32 SNPs. Only one candidate vQTL region overlapped between the two methods, on SSC7, which also contained the most significant SNP. Within this vQTL region, two candidate genes were identified, ADGRF1, which is involved in neurodevelopment of the brain, and ADGRF5, which is involved in the function of the respiratory system and in vascularization. The correlation between estimated breeding values based on the two methods was 0.86. Three-fold cross-validation indicated that DHGLM yielded EBV that were much more accurate and had better prediction of missing observations than LnVar. CONCLUSIONS: The results indicated that the LnVar and DHGLM methods resulted in genetically different traits. Based on their validation, we recommend the use of DHGLM over the simpler method of log-transformed variance of residuals. These conclusions can be useful for future studies on the evaluation of the variability of any trait in any species.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Animais , Feminino , Genômica , Tamanho da Ninhada de Vivíparos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Gravidez , Sus scrofa/genética , Suínos/genética
7.
Trop Anim Health Prod ; 54(1): 34, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978613

RESUMO

The objective of this study was to contribute to genetic improvement for carcass quality in Nellore cattle by estimating genetic parameters for carcass characteristics measured by traditional and novel ultrasound adjusted for body weight. Records of 19,910 Nellore breed animals born between 2001 and 2015 as part of a genetic improvement program were evaluated for this purpose. The (co)variance components and genetic parameters for yearling weight (YW), slaughter conformation at yearling age (SCY), ribeye area (REA), REA adjusted for 100 kg of body weight (REA100), REA adjusted for 450 kg of body weight (REA450), subcutaneous fat thickness over the loin (SFTL) and the rump (SFTR), intramuscular fat (IF), and height × width ratio of the sirloin steak (RATIO) were estimated using the restricted maximum likelihood (REML) method and the three-trait animal model. The estimated heritability values were 0.39 (YW), 0.33 (SCY), 0.31 (REA), 0.42 (REA100), 0.38 (REA450), 0.31 (RATIO), 0.17 (SFTL), 0.27 (SFTR), and 0.41 (MAR). The genetic correlations between REA and YW (0.43) and SCY and YW (0.78), respectively, suggested that selecting for REA or SCY could result in an increase in body weight. Because of its moderate and negative correlation with YW, REA100 was ineffective as a muscling indicator (- 0.38). The indicators REA450 and RATIO had a - 0.12 and 0.11 low correlation with YW, respectively. Thus, it is concluded that REA450 and RATIO were the best indicators of muscling, with heritability of medium magnitude, making the selection viable, as well as having a low correlation with body weight.


Assuntos
Modelos Genéticos , Músculos , Animais , Peso Corporal , Bovinos/genética , Fenótipo , Ultrassonografia/veterinária
8.
Artigo em Chinês | MEDLINE | ID: mdl-34979615

RESUMO

Objective:To identify the deaf-causing mutation by the genetic analysis in a family with non-syndromic hereditary deafness. Methods:Medical history collection, hearing, vision, and genome whole-exome sequencing were performed on the members of the deaf family. Results:Two mutation sites were identified in the MYO7A gene, namely c.1183C>T and 1496T>C, of which c.1183C>T has a small number of foreign literature reports, and 1496T>C is a newly discovered mutation site. According to ACMG mutation guideline showed that these two mutations were pathogenic mutations of the proband. Sanger sequencing verified that c.1183C>T was derived from the father, and 1496T>C was derived from the mother. These two mutation sites were not found in the healthy population in the Exome Sequencing Project(ESP6500) database, 1000 Genomes Project database, and the Gnomad database. Moreover, the second child in this family included a heterozygous mutation of c.1183C>T and 1496T>C and was confirmed to become severe sensorineural deaf. Conclusion:A new pathogenic compound heterozygous mutation in the MYO7A gene has been discovered, which provides more diagnostic evidence for the autosomal recessive non-syndromic deafness caused by the MYO7A gene mutation and improves the prenatal gene diagnosis in high-risk families for mutation carriers to reduce congenital disabilities.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Criança , Surdez/genética , Perda Auditiva Neurossensorial/genética , Heterozigoto , Humanos , Mutação , Linhagem , Fenótipo
9.
BMC Plant Biol ; 22(1): 5, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979924

RESUMO

BACKGROUND: Upland Cotton (Gossypium hirsutum L.) has few cotton varieties suitable for mechanical harvesting. The plant height of the cultivar is one of the key features that need to modify. Hence, this study was planned to locate the QTL for plant height in a 60Co γ treated upland cotton semi-dwarf mutant Ari1327. RESULTS: Interestingly, bulk segregant analysis (BSA) and genotyping by sequencing (GBS) methods exhibited that candidate QTL was co-located in the region of 5.80-9.66 Mb at D01 chromosome in two F2 populations. Using three InDel markers to genotype a population of 1241 individuals confirmed that the offspring's phenotype is consistent with the genotype. Comparative analysis of RNA-seq between the mutant and wild variety exhibited that Gh_D01G0592 was identified as the source of dwarfness from 200 genes. In addition, it was also revealed that the appropriate use of partial separation markers in QTL mapping can escalate linkage information. CONCLUSIONS: Overwhelmingly, the results will provide the basis to reveal the function of candidate genes and the utilization of excellent dwarf genetic resources in the future.


Assuntos
Cromossomos de Plantas/genética , Ligação Genética , Genótipo , Gossypium/genética , Fenótipo , Locos de Características Quantitativas , Mapeamento Cromossômico , Melhoramento Vegetal
10.
Appl Environ Microbiol ; 88(1): e0153121, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015978

RESUMO

Clostridium thermocellum is a thermophilic, anaerobic bacterium that natively ferments cellulose to ethanol and is a candidate for cellulosic biofuel production. Recently, we identified a hypermutator strain of C. thermocellum with a C669Y mutation in the polC gene, which encodes a DNA polymerase III enzyme. Here, we reintroduced this mutation using recently developed CRISPR tools to demonstrate that this mutation is sufficient to recreate the hypermutator phenotype. The resulting strain shows an approximately 30-fold increase in the mutation rate. This mutation is hypothesized to function by interfering with metal ion coordination in the PHP (polymerase and histidinol phosphatase) domain, which is responsible for proofreading. The ability to selectively increase the mutation rate in C. thermocellum is a useful tool for future directed evolution experiments. IMPORTANCE Cellulosic biofuels are a promising approach to decarbonize the heavy-duty-transportation sector. A longstanding barrier to cost-effective cellulosic biofuel production is the recalcitrance of cellulose to solubilization. Native cellulose-consuming organisms, such as Clostridium thermocellum, are promising candidates for cellulosic biofuel production; however, they often need to be genetically modified to improve product formation. One approach is adaptive laboratory evolution. Our findings demonstrate a way to increase the mutation rate in this industrially relevant organism, which can reduce the time needed for adaptive evolution experiments.


Assuntos
Clostridium thermocellum , Composição de Bases , Clostridium thermocellum/genética , DNA Polimerase III , Nucleotídeos , Fenótipo , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA
11.
Braz J Biol ; 84: e255235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35019108

RESUMO

In soybean breeding program, continuous selection pressure on traits response to yield created a genetic bottleneck for improvements of soybean through hybridization breeding technique. Therefore an initiative was taken to developed high yielding soybean variety applying mutation breeding techniques at Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture (BINA), Bangladesh. Locally available popular cultivar BARI Soybean-5 was used as a parent material and subjected to five different doses of Gamma ray using Co60. In respect to seed yield and yield attributing characters, twelve true breed mutants were selected from M4 generation. High values of heritability and genetic advance with high genotypic coefficient of variance (GCV) for plant height, branch number and pod number were considered as favorable attributes for soybean improvement that ensure expected yield. The mutant SBM-18 obtained from 250Gy provided stable yield performance at diversified environments. It provided maximum seed yield of 3056 kg ha-1 with highest number of pods plant-1 (56). The National Seed Board of Bangladesh (NSB) eventually approved SBM-18 and registered it as a new soybean variety named 'Binasoybean-5' for large-scale planting because of its superior stability in various agro-ecological zones and consistent yield performance.


Assuntos
Soja , Bangladesh , Genótipo , Mutação , Fenótipo , Melhoramento Vegetal , Soja/genética , Soja/crescimento & desenvolvimento
12.
BMC Mol Cell Biol ; 23(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979904

RESUMO

BACKGROUND: Uncontrolled growth in solid breast cancer generates mechanical compression that may drive the cancer cells into a more invasive phenotype, but little is known about how such compression affects the key events and corresponding regulatory mechanisms associated with invasion of breast cancer cells including cellular behaviors and matrix degradation. RESULTS: Here we show that compression enhanced invasion and matrix degradation of breast cancer cells. We also identified Piezo1 as the putative mechanosensitive cellular component that transmitted compression to not only enhance the invasive phenotype, but also induce calcium influx and downstream Src signaling. Furthermore, we demonstrated that Piezo1 was mainly localized in caveolae, and both Piezo1 expression and compression-enhanced invasive phenotype of the breast cancer cells were reduced when caveolar integrity was compromised by either knocking down caveolin1 expression or depleting cholesterol content. CONCLUSIONS: Taken together, our data indicate that mechanical compression activates Piezo1 channels to mediate enhanced breast cancer cell invasion, which involves both cellular events and matrix degradation. This may be a critical mechanotransduction pathway during breast cancer metastasis, and thus potentially a novel therapeutic target for the disease.


Assuntos
Neoplasias da Mama , Canais Iônicos , Mecanotransdução Celular , Feminino , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Fenótipo , Transdução de Sinais
13.
BMC Ophthalmol ; 22(1): 22, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022017

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disease, involving both environmental and genetic factors; The purpose of this study is to evaluate the clinical presentations and genetic variants in Chinese patients with ROP. METHODS: A total of 36 patients diagnosed with ROP were enrolled in this study, their medical and ophthalmic histories were obtained, and comprehensive clinical examinations were performed. Genomic DNA was isolated from peripheral blood of ROP patients, polymerase chain reaction and direct sequencing of the associated pathogenic genes (FZD4, TSPAN12, and NDP) were performed. RESULTS: All patients exhibited the clinical manifestations of ROP. No mutations were detected in the TSPAN12 and NDP genes in all patients; Interestingly, three novel missense mutations were identified in the FZD4 gene (p.A2P, p.L79M, and p.Y378C) in four patients, for a detection rate of 11.1% (4/36). CONCLUSIONS: This study expands the genotypic spectrum of FZD4 gene in ROP patients, and our findings underscore the importance of obtaining molecular analyses and comprehensive health screening for this retinal disease.


Assuntos
Retinopatia da Prematuridade , Proteínas do Olho/genética , Receptores Frizzled/genética , Humanos , Recém-Nascido , Mutação , Proteínas do Tecido Nervoso/genética , Fenótipo , Retinopatia da Prematuridade/genética , Tetraspaninas/genética
14.
BMC Ophthalmol ; 22(1): 27, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35033039

RESUMO

BACKGROUND: Retinitis pigmentosa (RP) is a genetically heterogeneous disease with 89 causative genes identified to date. However, only approximately 60% of RP cases genetically solved to date, predicating that many novel disease-causing variants are yet to be identified. The purpose of this study is to identify novel variants in PDE6A and PDE6B genes and present its phenotypes in patients with retinitis pigmentosa in Chinese families. METHODS: Five retinitis pigmentosa patients with PDE6A variants and three with PDE6B variants were identified through a hereditary eye disease enrichment panel (HEDEP), all patients' medical and ophthalmic histories were collected, and ophthalmological examinations were performed, followed by an analysis of the possible causative variants. Sanger sequencing was used to verify the variants. RESULTS: We identified 20 variants in eight patients: 16 of them were identified in either PDE6A or PDE6B in a compound heterozygous state. Additional four heterozygous variants were identified in the genes ADGRA3, CA4, OPTN, RHO. Two novel genetic changes in PDE6A were identified (c.1246G > A and c.1747 T > A), three novel genetic changes in PDE6B were identified (c.401 T > C, c.2293G > C and c.1610-1612del), out of the novel identified variants one was most probably non-pathogenic (c.2293G > C), all other novel variants are pathogenic. Additional variant was identified in CA4 and RHO, which can cause ADRP (c.243G > A, c.688G > A). In addition, a novel variant in ADGRA3 was identified (c.921-1G > A). CONCLUSIONS: This study reveals novel and known variants in PDE6A and PDE6B genes in Chinese families with autosomal recessive RP, and expands the clinical and genetic findings of photoreceptor-specific enzyme deficiencies.


Assuntos
Proteínas do Olho , Retinite Pigmentosa , China/epidemiologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 6/genética , Proteínas do Olho/genética , Humanos , Mutação , Linhagem , Fenótipo , Retinite Pigmentosa/genética
15.
Planta ; 255(2): 40, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038036

RESUMO

MAIN CONCLUSION: QTL hotspots identified for selected source-sink-related traits provide the opportunity for pyramiding favorable alleles for improving sorghum productivity under diverse environments. A sorghum bi-parental mapping population was evaluated under six different environments at Hays and Manhattan, Kansas, USA, in 2016 and 2017, to identify genomic regions controlling source-sink relationships. The population consisted of 210 recombinant inbred lines developed from US elite post-flowering drought susceptible (RTx430) and a known post-flowering drought tolerant cultivar (SC35). Selected physiological traits related to source (effective quantum yield of photosystem II and chlorophyll index), sink (grain yield per panicle) and panicle neck diameter were recorded during grain filling. The results showed strong phenotypic and genotypic association between panicle neck diameter and grain yield per panicle during mid-grain filling and at maturity. Multiple QTL model revealed 5-12 including 2-5 major QTL for each trait. Among them 3, 7 and 8 QTL for quantum yield, panicle neck diameter and chlorophyll index, respectively, have not been identified previously in sorghum. Phenotypic variation explained by QTL identified across target traits ranged between 5.5 and 25.4%. Panicle neck diameter and grain yield per panicle were positively associated, indicating the possibility of targeting common co-localized QTL to improve both traits simultaneously through marker-assisted selection. Three major QTL hotspots, controlling multiple traits were identified on chromosome 1 (52.23-61.18 Mb), 2 (2.52-11.43 Mb) and 3 (1.32-3.95 Mb). The identified genomic regions and underlying candidate genes can be utilized in pyramiding favorable alleles for improving source-sink relationships in sorghum under diverse environments.


Assuntos
Sorghum , Mapeamento Cromossômico , Grão Comestível/genética , Fenótipo , Locos de Características Quantitativas/genética , Sorghum/genética
16.
Int J Cancer ; 150(1): 132-141, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34287840

RESUMO

Although cancer is highly heterogeneous, all metastatic cancer is considered American Joint Committee on Cancer (AJCC) Stage IV disease. The purpose of this project was to redefine staging of metastatic cancer. Internal validation of nationally representative patient data from the National Cancer Database (n = 461 357; 2010-2013), and external validation using the Surveillance, Epidemiology and End Results database (n = 106 595; 2014-2015) were assessed using the concordance index for evaluation of survival prediction. A Cox proportional hazards model was used for overall survival by considering identified phenotypes (latent classes) and other confounding variables. Latent class analysis was performed for phenotype identification, where Bayesian information criterion (BIC) and sample-size-adjusted BIC were used to select the optimal number of distinct clusters. Kappa coefficients assessed external cluster validation. Latent class analysis identified five metastatic phenotypes with differences in overall survival (P < .0001): (Stage IVA) nearly exclusive bone-only metastases (n = 59 049, 12.8%; median survival 12.7 months; common in lung, breast and prostate cancers); (IVB) predominant lung metastases (n = 62 491, 13.5%; 11.4 months; common in breast, stomach, kidney, ovary, uterus, thyroid, cervix and soft tissue cancers); (IVC) predominant liver/lung metastases (n = 130 014, 28.2%; 7.0 months; common in colorectum, pancreatic, lung, esophagus and stomach cancers); (IVD) bone/liver/lung metastases predominant over brain (n = 61 004, 13.2%; 5.9 months; common in lung and breast cancers); and (IVE) brain/lung metastases predominant over bone/liver (n = 148 799, 32.3%; 5.7 months; lung cancer and melanoma). Long-term survivors were identified, particularly in Stages IVA-B. A pan-cancer nomogram model to predict survival (STARS: site, tumor, age, race, sex) was created, validated and provides 13% better prognostication than AJCC: 1-month concordance index of 0.67 (95% confidence interval [CI]: 0.66-0.67) vs 0.61 (95% CI: 0.60-0.61). STARS is simple, uses easily accessible variables, better prognosticates survival outcomes and provides a platform to develop novel metastasis-directed clinical trials.


Assuntos
Neoplasias/patologia , Nomogramas , Fenótipo , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Taxa de Sobrevida , Adulto Jovem
17.
Int J Cancer ; 150(2): 362-373, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34486752

RESUMO

The role of fibroblast APC mutation in carcinogenesis is not clear. Apc+/- colon fibroblasts have been previously characterized: however, little is known about their behavior at very early-stage of colon carcinogenesis. We cultured colon mucosa fibroblasts (PCF, Apc+/- ) of Pirc rats (F344/NTac-Apcam1137 ) at an early stage of tumorigenesis, in absence of preneoplastic lesions, and of age-matched wt (WCF): DNA damage levels, inflammatory phenotype and the expression of known markers of CAFs were analyzed. The latter were also assessed by microarray analysis on colon normal mucosa of Pirc and wt animals. PCF exhibited higher proliferative rates (P < .001) and delayed replicative senescence onset (P < .05) compared to WCF, along with a lower level of oxidative DNA damage (P < .05). Furthermore, a constitutively higher expression of COX-2 and sensitivity to inflammatory stimuli was found in PCF compared to WCF (P < .05), accompanied by higher invasive capability (P < .05) and presence of cytoplasmic chromatin foci (cytoplasmic chromatin foci, P < .05). However, they neither expressed CAFs markers (α-SMA, IL-6) nor responded to CAFs activating stimuli (TGF-ß). Accordingly, CAFs markers and activating stimuli resulted down-regulated in Pirc normal mucosa compared to wt, whereas DNA damage response and tolerance pathways were overexpressed. These data show for the first time that a proliferative and inflammatory phenotype characterizes Apc+/- colon fibroblasts since very early stages of colon tumorigenesis, and indicate a role of Apc mutation in driving fibroblast phenotypic alterations that could support the establishment of a protumorigenic environment. Early pharmacological targeting of these dysfunctions might impact on tumor prevention in FAP patients.


Assuntos
Proliferação de Células , Colo/patologia , Neoplasias do Colo/patologia , Dano ao DNA , Fibroblastos/patologia , Genes APC , Inflamação/patologia , Animais , Apoptose , Colo/metabolismo , Neoplasias do Colo/etiologia , Neoplasias do Colo/metabolismo , Fibroblastos/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Mutação , Fenótipo , Ratos , Ratos Endogâmicos F344
18.
Gene ; 809: 146048, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34756963

RESUMO

Colonization of the squid Euprymna scolopes by the bacterium Vibrio fischeri depends on bacterial biofilm formation, motility, and bioluminescence. Previous work has demonstrated an inhibitory role for the small RNA (sRNA) Qrr1 in quorum-induced bioluminescence of V. fischeri, but the contribution of the corresponding sRNA chaperone, Hfq, was not examined. We thus hypothesized that V. fischeri Hfq similarly functions to inhibit bacterial bioluminescence as well as regulate other key steps of symbiosis, including bacterial biofilm formation and motility. Surprisingly, deletion of hfq increased luminescence of V. fischeri beyond what was observed for the loss of qrr1 sRNA. Epistasis experiments revealed that, while Hfq contributes to the Qrr1-dependent regulation of light production, it also functions independently of Qrr1 and its downstream target, LitR. This Hfq-dependent, Qrr1-independent regulation of bioluminescence is also independent of the major repressor of light production in V. fischeri, ArcA. We further determined that Hfq is required for full motility of V. fischeri in a mechanism that partially depends on the Qrr1/LitR regulators. Finally, Hfq also appears to function in the control of biofilm formation: loss of Hfq delayed the timing and diminished the extent of wrinkled colony development, but did not eliminate the production of SYP-polysaccharide-dependent cohesive colonies. Furthermore, loss of Hfq enhanced production of cellulose and resulted in increased Congo red binding. Together, these findings point to Hfq as an important regulator of multiple phenotypes relevant to symbiosis between V. fischeri and its squid host.


Assuntos
Aliivibrio fischeri/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , RNA Interferente Pequeno/metabolismo , Aliivibrio fischeri/crescimento & desenvolvimento , Biofilmes/crescimento & desenvolvimento , Celulose/metabolismo , Regulação Bacteriana da Expressão Gênica , Luminescência , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Fenótipo
19.
Arch Oral Biol ; 133: 105287, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34768057

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis of studies that evaluated the association between gingival phenotype (GP) and the underlying alveolar bone thickness (ABT). DESIGN: An electronic search was performed in PubMed, Embase, Scopus, ProQuest, and Web of Science. The following inclusion criteria were applied: English original studies that compared the ABT in periodontally healthy patients presenting thin versus thick GPs. Studies that evaluated the correlation between gingival thickness (GT) and ABT were also included. Pooled mean difference (95% confidence interval) was estimated using random-effects maximum likelihood model meta-analysis. RESULTS: From a total of 1427 retrieved articles, 17 were included. The majority of eight studies that compared the ABT between thick and thin GPs, reported a significantly greater ABT associated with a thick phenotype. Based on the meta-analysis results of six studies, the mean difference between the two phenotypes (0.33 mm) was statistically significant (P < 0.01). The majority of ten studies that investigated the correlation between GT and ABT evidenced a significant positive correlation (r = 0.11 -0.49). The association was more evident in the crestal areas and decreased toward the apex. CONCLUSIONS: There is contradictory evidence concerning the correlation between soft and hard tissue thickness; however, the meta-analysis revealed a significantly thicker alveolar plate in the presence of a thick phenotype. Since the evaluation of GP could be simply performed using a periodontal probe, such a relationship could provide clinical perspective at the initial examination. This is particularly beneficial in procedures affecting periodontal structures, including immediate implant placement and orthodontic treatments.


Assuntos
Gengiva , Humanos , Fenótipo
20.
Phytochemistry ; 193: 113002, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34768187

RESUMO

Higher hydroxycinnamate content makes maize tissues more recalcitrant to damage by insects, less digestible by ruminants, and less suitable for biofuel production. In a Genome Wide Association Analysis (GWAS) study carried out in a maize MAGIC population, we identified 24 SNPs associated with esterified cell wall-bound hydroxycinnamates, that represented 15 Quantitative Traic Loci (QTL). We identified new genomic regions associated to cell wall bound hydroxycinnamates in maize stover that could have an impact on their content across different genetic backgrounds. The high resolution QTL described in this study could be valuable for addressing positional mapping of genes involved in hydroxycinnamate biosynthesis and could uncover genes implicated in the esterification of hydroxycinnamic acids to the arabinoxylan chains that are poorly understood. However, we found that genetic correlation coefficients between hydroxycinnamate content and economical important traits such as saccharification efficiency, animal digestibility andi pest resistance were low to moderate, so modify specific hydroxycinnamates to indirectly improve cultivar performance will be unsuitable.


Assuntos
Polimorfismo de Nucleotídeo Único , Zea mays , Animais , Parede Celular , Estudo de Associação Genômica Ampla , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Zea mays/genética
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