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1.
Nat Commun ; 12(1): 3420, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103535

RESUMO

Theory shows how sexual selection can exaggerate male traits beyond naturally selected optima and also how natural selection can ultimately halt trait elaboration. Empirical evidence supports this theory, but to our knowledge, there have been no experimental evolution studies directly testing this logic, and little examination of possible associated effects on female fitness. Here we use experimental evolution of replicate populations of broad-horned flour beetles to test for effects of sex-specific predation on an exaggerated sexually selected male trait (the mandibles), while also testing for effects on female lifetime reproductive success. We find that populations subjected to male-specific predation evolve smaller sexually selected mandibles and this indirectly increases female fitness, seemingly through intersexual genetic correlations we document. Predation solely on females has no effects. Our findings support fundamental theory, but also reveal unforseen outcomes-the indirect effect on females-when natural selection targets sex-limited sexually selected characters.


Assuntos
Besouros/genética , Aptidão Genética , Característica Quantitativa Herdável , Seleção Genética , Caracteres Sexuais , Animais , Evolução Biológica , Tamanho Corporal , Cruzamento , Feminino , Variação Genética , Masculino , Mandíbula/anatomia & histologia , Tamanho do Órgão , Fenótipo , Comportamento Predatório
2.
BMC Genomics ; 22(1): 432, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107879

RESUMO

BACKGROUND: Circulating white blood cell and platelet traits are clinically linked to various disease outcomes and differ across individuals and ancestry groups. Genetic factors play an important role in determining these traits and many loci have been identified. However, most of these findings were identified in populations of European ancestry (EA), with African Americans (AA), Hispanics/Latinos (HL), and other races/ethnicities being severely underrepresented. RESULTS: We performed ancestry-combined and ancestry-specific genome-wide association studies (GWAS) for white blood cell and platelet traits in the ancestrally diverse Population Architecture using Genomics and Epidemiology (PAGE) Study, including 16,201 AA, 21,347 HL, and 27,236 EA participants. We identified six novel findings at suggestive significance (P < 5E-8), which need confirmation, and independent signals at six previously established regions at genome-wide significance (P < 2E-9). We confirmed multiple previously reported genome-wide significant variants in the single variant association analysis and multiple genes using PrediXcan. Evaluation of loci reported from a Euro-centric GWAS indicated attenuation of effect estimates in AA and HL compared to EA populations. CONCLUSIONS: Our results highlighted the potential to identify ancestry-specific and ancestry-agnostic variants in participants with diverse backgrounds and advocate for continued efforts in improving inclusion of racially/ethnically diverse populations in genetic association studies for complex traits.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Genômica , Humanos , Leucócitos , Fenótipo
3.
Vasc Health Risk Manag ; 17: 273-298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103921

RESUMO

COVID-19 sepsis is characterized by acute respiratory distress syndrome (ARDS) as a consequence of pulmonary tropism of the virus and endothelial heterogeneity of the host. ARDS is a phenotype among patients with multiorgan dysfunction syndrome (MODS) due to disseminated vascular microthrombotic disease (VMTD). In response to the viral septicemia, the host activates the complement system which produces terminal complement complex C5b-9 to neutralize pathogen. C5b-9 causes pore formation on the membrane of host endothelial cells (ECs) if CD59 is underexpressed. Also, viral S protein attraction to endothelial ACE2 receptor damages ECs. Both affect ECs and provoke endotheliopathy. Disseminated endotheliopathy activates two molecular pathways: inflammatory and microthrombotic. The former releases inflammatory cytokines from ECs, which lead to inflammation. The latter initiates endothelial exocytosis of unusually large von Willebrand factor (ULVWF) multimers and FVIII from Weibel-Palade bodies. If ADAMTS13 is insufficient, ULVWF multimers activate intravascular hemostasis of ULVWF path. In activated ULVWF path, ULVWF multimers anchored to damaged endothelial cells recruit circulating platelets and trigger microthrombogenesis. This process produces "microthrombi strings" composed of platelet-ULVWF complexes, leading to endotheliopathy-associated VMTD (EA-VMTD). In COVID-19, microthrombosis initially affects the lungs per tropism causing ARDS, but EA-VMTD may orchestrate more complex clinical phenotypes, including thrombotic thrombocytopenic purpura (TTP)-like syndrome, hepatic coagulopathy, MODS and combined micro-macrothrombotic syndrome. In this pandemic, ARDS and pulmonary thromboembolism (PTE) have often coexisted. The analysis based on two hemostatic theories supports ARDS caused by activated ULVWF path is EA-VMTD and PTE caused by activated ULVWF and TF paths is macrothrombosis. The thrombotic disorder of COVID-19 sepsis is consistent with the notion that ARDS is virus-induced disseminated EA-VMTD and PTE is in-hospital vascular injury-related macrothrombosis which is not directly  related to viral pathogenesis. The pathogenesis-based therapeutic approach is discussed for the treatment of EA-VMTD with antimicrothrombotic regimen and the potential need of anticoagulation therapy for coinciding macrothrombosis in comprehensive COVID-19 care.


Assuntos
COVID-19/epidemiologia , Células Endoteliais/metabolismo , Fibrinolíticos/uso terapêutico , Hemostasia/fisiologia , SARS-CoV-2 , Sepse/complicações , Trombose/etiologia , COVID-19/complicações , Humanos , Pandemias , Fenótipo , Sepse/metabolismo , Trombose/tratamento farmacológico , Trombose/metabolismo
4.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072501

RESUMO

d-type cyclins (CYCDs) are a special class of cyclins and play extremely important roles in plant growth and development. In the plant kingdom, most of the existing studies on CYCDs have been done on herbaceous plants, with few on perennial woody plants. Here, we identified a Populus d-type cyclin gene, PsnCYCD1;1, which is mainly transcribed in leaf buds and stems. The promoter of PsnCYCD1;1 activated GUS gene expression and transgenic Arabidopsis lines were strongly GUS stained in whole seedlings and mature anthers. Moreover, subcellular localization analysis showed the fluorescence signal of PsnCYCD1;1-GFP fusion protein is present in the nucleus. Furthermore, overexpression of the PsnCYCD1;1 gene in Arabidopsis can promote cell division and lead to small cell generation and cytokinin response, resulting in curved leaves and twisted inflorescence stems. Moreover, the transcriptional levels of endogenous genes, such as ASs, KNATs, EXP10, and PHB, were upregulated by PsnCYCD1;1. Together, our results indicated that PsnCYCD1;1 participates in cell division by cytokinin response, providing new information on controlling plant architecture in woody plants.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Divisão Celular/genética , Ciclina D3/genética , Expressão Gênica , Folhas de Planta/genética , Populus/genética , Proteínas de Arabidopsis/metabolismo , Clonagem Molecular , Ciclina D3/metabolismo , Regulação da Expressão Gênica de Plantas , Morfogênese/genética , Especificidade de Órgãos , Fenótipo , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Transporte Proteico
5.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072552

RESUMO

Indirect evidence has determined the possibility that microplastics (MP) induce constipation, although direct scientific proof for constipation induction in animals remains unclear. To investigate whether oral administration of polystyrene (PS)-MP causes constipation, an alteration in the constipation parameters and mechanisms was analyzed in ICR mice, treated with 0.5 µm PS-MP for 2 weeks. Significant alterations in water consumption, stool weight, stool water contents, and stool morphology were detected in MP treated ICR mice, as compared to Vehicle treated group. Also, the gastrointestinal (GI) motility and intestinal length were decreased, while the histopathological structure and cytological structure of the mid colon were remarkably altered in treated mice. Mice exposed to MP also showed a significant decrease in the GI hormone concentration, muscarinic acetylcholine receptors (mAChRs) expression, and their downstream signaling pathway. Subsequent to MP treatment, concentrations of chloride ion and expressions of its channel (CFTR and CIC-2) were decreased, whereas expressions of aquaporin (AQP)3 and 8 for water transportation were downregulated by activation of the mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB signaling pathway. These results are the first to suggest that oral administration of PS-MP induces chronic constipation through the dysregulation of GI motility, mucin secretion, and chloride ion and water transportation in the mid colon.


Assuntos
Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Microplásticos/efeitos adversos , Fenótipo , Poliestirenos/efeitos adversos , Animais , Comportamento Animal , Biomarcadores , Fenômenos Químicos , Cloretos/metabolismo , Colo/patologia , Colo/ultraestrutura , Modelos Animais de Doenças , Suscetibilidade a Doenças , Hormônios Gastrointestinais/metabolismo , Motilidade Gastrointestinal , Bombas de Íon/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Microplásticos/química , Mucinas/metabolismo , Poliestirenos/química , Transdução de Sinais , Água/metabolismo
6.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072586

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.


Assuntos
Deficiência de Colina/complicações , Dieta Hiperlipídica/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Animais , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Gluconeogênese , Mediadores da Inflamação/metabolismo , Gotículas Lipídicas/metabolismo , Metabolismo dos Lipídeos , Lipogênese , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/patologia , Fenótipo
7.
Int J Mol Sci ; 22(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34069068

RESUMO

MADS-box genes are involved in various developmental processes including vegetative development, flower architecture, flowering, pollen formation, seed and fruit development. However, the function of most MADS-box genes and their regulation mechanism are still unclear in woody plants compared with model plants. In this study, a MADS-box gene (CiMADS43) was identified in citrus. Phylogenetic and sequence analysis showed that CiMADS43 is a GOA-like Bsister MADS-box gene. It was localized in the nucleus and as a transcriptional activator. Overexpression of CiMADS43 promoted early flowering and leaves curling in transgenic Arabidopsis. Besides, overexpression or knockout of CiMADS43 also showed leaf curl phenotype in citrus similar to that of CiMADS43 overexpressed in Arabidopsis. Protein-protein interaction found that a SEPALLATA (SEP)-like protein (CiAGL9) interacted with CiMADS43 protein. Interestingly, CiAGL9 also can bind to the CiMADS43 promoter and promote its transcription. Expression analysis also showed that these two genes were closely related to seasonal flowering and the development of the leaf in citrus. Our findings revealed the multifunctional roles of CiMADS43 in the vegetative and reproductive development of citrus. These results will facilitate our understanding of the evolution and molecular mechanisms of MADS-box genes in citrus.


Assuntos
Citrus/crescimento & desenvolvimento , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Proteínas de Domínio MADS/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Domínios e Motivos de Interação entre Proteínas , Sequência de Aminoácidos , Citrus/genética , Citrus/metabolismo , Flores/genética , Flores/metabolismo , Proteínas de Domínio MADS/genética , Fenótipo , Filogenia , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Homologia de Sequência
8.
BMC Pediatr ; 21(1): 256, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074259

RESUMO

BACKGROUND: Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of chronic encephalopathies characterized by epilepsy with comorbid intellectual disability that are frequently associated with de novo nonsynonymous coding variants in ion channels, cell-surface receptors, and other neuronally expressed genes. Mutations in TRPM3 were identified as the cause of DEE. We report a novel patient with DEE carrying a de novo missense mutation in TRPM3, p.(S1202T); this missense mutation has never been reported. CASE PRESENTATION: A 7-year and 2-month-old Chinese patient who had recurrent polymorphic seizures was clinically diagnosed with DEE. A de novo missense mutation in TRPM3, which has not yet been reported, was identified in this case. The patient had a clinical phenotype consistent with previous reports. CONCLUSIONS: These findings could expand the spectrum of TRPM3 mutations and might also support that de novo substitutions of TRPM3 are a cause of DEE.


Assuntos
Epilepsia , Deficiência Intelectual , Canais de Cátion TRPM , Criança , China , Epilepsia/genética , Humanos , Lactente , Deficiência Intelectual/genética , Mutação , Mutação de Sentido Incorreto , Fenótipo , Canais de Cátion TRPM/genética
9.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069993

RESUMO

Rett syndrome (RTT) is a rare neurodevelopmental disorder that is usually caused by mutations of the MECP2 gene. Patients with RTT suffer from severe deficits in motor, perceptual and cognitive domains. Electroencephalogram (EEG) has provided useful information to clinicians and scientists, from the very first descriptions of RTT, and yet no reliable neurophysiological biomarkers related to the pathophysiology of the disorder or symptom severity have been identified to date. To identify consistently observed and potentially informative EEG characteristics of RTT pathophysiology, and ascertain areas most worthy of further systematic investigation, here we review the literature for EEG abnormalities reported in patients with RTT and in its disease models. While pointing to some promising potential EEG biomarkers of RTT, our review identify areas of need to realize the potential of EEG including (1) quantitative investigation of promising clinical-EEG observations in RTT, e.g., shift of mu rhythm frequency and EEG during sleep; (2) closer alignment of approaches between patients with RTT and its animal models to strengthen the translational significance of the work (e.g., EEG measurements and behavioral states); (3) establishment of large-scale consortium research, to provide adequate Ns to investigate age and genotype effects.


Assuntos
Eletroencefalografia , Síndrome de Rett/diagnóstico , Síndrome de Rett/fisiopatologia , Animais , Biomarcadores , Modelos Animais de Doenças , Progressão da Doença , Fenômenos Eletrofisiológicos , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG/deficiência , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/fisiologia , Camundongos , Mutação , Fenótipo , Ratos , Síndrome de Rett/genética , Pesquisa Médica Translacional
10.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070033

RESUMO

Drought response in wheat is considered a highly complex process, since it is a multigenic trait; nevertheless, breeding programs are continuously searching for new wheat varieties with characteristics for drought tolerance. In a previous study, we demonstrated the effectiveness of a mutant known as RYNO3936 that could survive 14 days without water. In this study, we reveal another mutant known as BIG8-1 that can endure severe water deficit stress (21 days without water) with superior drought response characteristics. Phenotypically, the mutant plants had broader leaves, including a densely packed fibrous root architecture that was not visible in the WT parent plants. During mild (day 7) drought stress, the mutant could maintain its relative water content, chlorophyll content, maximum quantum yield of PSII (Fv/Fm) and stomatal conductance, with no phenotypic symptoms such as wilting or senescence despite a decrease in soil moisture content. It was only during moderate (day 14) and severe (day 21) water deficit stress that a decline in those variables was evident. Furthermore, the mutant plants also displayed a unique preservation of metabolic activity, which was confirmed by assessing the accumulation of free amino acids and increase of antioxidative enzymes (peroxidases and glutathione S-transferase). Proteome reshuffling was also observed, allowing slow degradation of essential proteins such as RuBisCO during water deficit stress. The LC-MS/MS data revealed a high abundance of proteins involved in energy and photosynthesis under well-watered conditions, particularly Serpin-Z2A and Z2B, SGT1 and Calnexin-like protein. However, after 21 days of water stress, the mutants expressed ABC transporter permeases and xylanase inhibitor protein, which are involved in the transport of amino acids and protecting cells, respectively. This study characterizes a new mutant BIG8-1 with drought-tolerant characteristics suited for breeding programs.


Assuntos
Secas , Mutação , Triticum/genética , Triticum/fisiologia , Aclimatação/genética , Aminoácidos/metabolismo , Antioxidantes/metabolismo , Clorofila/metabolismo , Metanossulfonato de Etila/toxicidade , Mutagênicos/toxicidade , Fenótipo , Complexo de Proteína do Fotossistema II/metabolismo , Melhoramento Vegetal , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Proteoma/metabolismo , Ribulose-Bifosfato Carboxilase/metabolismo , Estresse Fisiológico/genética , Triticum/efeitos dos fármacos , Água/metabolismo
11.
Int J Mol Sci ; 22(10)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34070080

RESUMO

In the last two decades, global environmental change has increased abiotic stress on plants and severely affected crops. For example, drought stress is a serious abiotic stress that rapidly and substantially alters the morphological, physiological, and molecular responses of plants. In Arabidopsis, several drought-responsive genes have been identified; however, the underlying molecular mechanism of drought tolerance in plants remains largely unclear. Here, we report that the "domain of unknown function" novel gene DUF569 (AT1G69890) positively regulates drought stress in Arabidopsis. The Arabidopsis loss-of-function mutant atduf569 showed significant sensitivity to drought stress, i.e., severe wilting at the rosette-leaf stage after water was withheld for 3 days. Importantly, the mutant plant did not recover after rewatering, unlike wild-type (WT) plants. In addition, atduf569 plants showed significantly lower abscisic acid accumulation under optimal and drought-stress conditions, as well as significantly higher electrolyte leakage when compared with WT Col-0 plants. Spectrophotometric analyses also indicated a significantly lower accumulation of polyphenols, flavonoids, carotenoids, and chlorophylls in atduf569 mutant plants. Overall, our results suggest that novel DUF569 is a positive regulator of the response to drought in Arabidopsis.


Assuntos
Aclimatação/genética , Arabidopsis/genética , Secas , Genes de Plantas , Ácido Abscísico/metabolismo , Aclimatação/fisiologia , Antioxidantes/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Peroxidação de Lipídeos , Mutação com Perda de Função , Fenótipo , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética
12.
Sensors (Basel) ; 21(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-34066716

RESUMO

Since conventional screening tools for assessing frailty phenotypes are resource intensive and unsuitable for routine application, efforts are underway to simplify and shorten the frailty screening protocol by using sensor-based technologies. This study explores whether machine learning combined with frailty modeling could determine the least sensor-derived features required to identify physical frailty and three key frailty phenotypes (slowness, weakness, and exhaustion). Older participants (n = 102, age = 76.54 ± 7.72 years) were fitted with five wearable sensors and completed a five times sit-to-stand test. Seventeen sensor-derived features were extracted and used for optimal feature selection based on a machine learning technique combined with frailty modeling. Mean of hip angular velocity range (indicator of slowness), mean of vertical power range (indicator of weakness), and coefficient of variation of vertical power range (indicator of exhaustion) were selected as the optimal features. A frailty model with the three optimal features had an area under the curve of 85.20%, a sensitivity of 82.70%, and a specificity of 71.09%. This study suggests that the three sensor-derived features could be used as digital biomarkers of physical frailty and phenotypes of slowness, weakness, and exhaustion. Our findings could facilitate future design of low-cost sensor-based technologies for remote physical frailty assessments via telemedicine.


Assuntos
Fragilidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Idoso Fragilizado , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Aprendizado de Máquina , Fenótipo
13.
Dis Aquat Organ ; 145: 21-33, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34080580

RESUMO

Sea star wasting disease (SSWD) refers to a suite of poorly described non-specific clinical signs including abnormal posture, epidermal ulceration, and limb autotomy (sloughing) causing mortalities of over 20 species of sea stars and subsequent ecological shifts throughout the northeastern Pacific. While SSWD is widely assumed to be infectious, with environmental conditions facilitating disease progression, few data exist on cellular changes associated with the disease. This is unfortunate, because such observations could inform mechanisms of disease pathogenesis and host susceptibility. Here, we replicated SSWD by exposing captive Pisaster ochraceus to a suite of non-infectious organic substances and show that development of gross lesions is a basal-to-surface process involving inflammation (e.g. infiltration of coelomocytes) of ossicles and mutable collagenous tissue, leading to epidermal ulceration. Affected sea stars also manifest increases in a heretofore undocumented coelomocyte type, spindle cells, that might be a useful marker of inflammation in this species. Finally, compared to purple morphs, orange P. ochraceus developed more severe lesions but survived longer. Longer-lived, and presumably more visible, severely-lesioned orange sea stars could have important demographic implications in terms of detectability of lesioned animals in the wild and measures of apparent prevalence of disease.


Assuntos
Estrelas-do-Mar , Síndrome de Emaciação , Animais , Fenótipo , Síndrome de Emaciação/veterinária
14.
BMC Plant Biol ; 21(1): 250, 2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34059007

RESUMO

BACKGROUND: Numerous quantitative trait loci (QTLs) and candidate genes associated with yield-related traits have been identified in cotton by genome-wide association study (GWAS) analysis. However, most of the phenotypic data were from a single or few environments, and the stable loci remained to be validated under multiple field environments. RESULTS: Here, 242 upland cotton accessions collected from different origins were continuously investigated for phenotypic data of four main yield components, including boll weight (BW) and lint percentage (LP) under 13 field environments, and boll number per plant (BN) and seed index (SI) under 11 environments. Correlation analysis revealed a positive correlation between BN and LP, BW and SI, while SI had a negative correlation with LP and BN. Genetic analysis indicated that LP had the highest heritability estimates of 94.97%, followed by 92.08% for SI, 86.09% for BW, and 72.92% for BN, indicating LP and SI were more suitable traits for genetic improvement. Based on 56,010 high-quality single nucleotide polymorphisms (SNPs) and GWAS analysis, a total of 95 non-redundant QTLs were identified, including 12 of BN, 23 of BW, 45 of LP, and 33 of SI, respectively. Of them, 10 pairs of homologous QTLs were detected between A and D sub-genomes. We also found that 15 co-located QTLs with more than two traits and 12 high-confidence QTLs were detected under more than six environments, respectively. Further, two NET genes (GH_A08G0716 and GH_A08G0783), located in a novel QTL hotspot (qtl24, qtl25 and qlt26) were predominately expressed in early fiber development stages, exhibited significant correlation with LP and SI. The GH_A07G1389 in the stable qtl19 region encoded a tetratricopeptide repeat (TPR)-like superfamily protein and was a homologous gene involved in short fiber mutant ligon lintless-y (Liy), implying important roles in cotton yield. CONCLUSIONS: The present study provides a foundation for understanding the regulatory mechanisms of yield components and may enhance yield improvement through molecular breeding in cotton.


Assuntos
Genes de Plantas , Gossypium/genética , Ecossistema , Estudo de Associação Genômica Ampla , Gossypium/crescimento & desenvolvimento , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
15.
Artigo em Inglês | MEDLINE | ID: mdl-34106824

RESUMO

Six bacterial strains isolated from root nodules of soybean plants that had been inoculated with root-zone soil of legumes native to Canada were previously characterized and 1) placed in two novel lineages within the genus Bradyrhizobium and 2) assigned to symbiovar septentrionale. Here we verified the taxonomic status of these strains using genomic and phenotypic analyses. Phylogenetic analyses of five protein encoding partial gene sequences as well as 52 full length ribosome protein subunit gene sequences confirmed placement of the novel strains in two highly supported lineages distinct from named Bradyrhizobium species. The highest average nucleotide identity values of strains representing these two lineages relative to type strains of closest relatives were 90.7 and 92.3% which is well below the threshold value for bacterial species circumscription. The genomes of representative strains 1S1T, 162S2 and 66S1MBT have sizes of 10598256, 10733150 and 9032145 bp with DNA G+C contents of 63.5, 63.4 and 63.8 mol%, respectively. These strains possess between one and three plasmids based on copy number of plasmid replication and segregation (repABC) genes. Novel strains also possess numerous insertion sequences, and, relative to reference strain Bradyrhizobium diazoefficiens USDA110T, exhibit inversion and fragmentation of nodulation (nod) and nitrogen-fixation (nif) gene clusters. Phylogenetic analyses of nodC and nifH gene sequences confirmed placement of novel strains in a distinct lineage corresponding to symbiovar septentrionale. Data for morphological, physiological and symbiotic characteristics complement the sequence-based results. The data presented here support the description of two new species for which the names Bradyrhizobium septentrionale sp. nov. (sv. septentrionale) and Bradyrhizobium quebecense sp. nov. (sv. septentrionale) are proposed, with 1S1T (=LMG 29930T=HAMBI 3676T) and 66S1MBT (=LMG 31547T=HAMBI 3720T) as type strains, respectively.


Assuntos
Bradyrhizobium/genética , Bradyrhizobium/fisiologia , Fabaceae/microbiologia , Rearranjo Gênico , Mutagênese Insercional/genética , Simbiose/genética , Composição de Bases , Sequência de Bases , Teorema de Bayes , Bradyrhizobium/classificação , Canadá , Fenótipo , Filogenia , Nodulação/genética , RNA Ribossômico 16S/genética , Subunidades Ribossômicas/genética , Nódulos Radiculares de Plantas/microbiologia
16.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(6): 593-600, 2021 Jun 24.
Artigo em Chinês | MEDLINE | ID: mdl-34126727

RESUMO

Objective: To analyze the clinical and genetic characteristics of clinical subtypes of non-obstructive hypertrophic cardiomyopathy (HCM). Methods: It was a cohort study. Patients with non-obstructive HCM admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, from January 1999 to April 2019 were enrolled. According to the characteristics of cardiac morphology and function shown by echocardiography, the patients were divided into common type, dilated type, restricted type and reduced ejection fraction type. The clinical data of the patients were recorded, and 8 sarcomere pathogenic genes were screened by full exon sequencing or panel sequencing. Patienst were followed up and cardiovascular endpoint events were recorded. Results: A total of 815 patients with non-obstructive HCM were enrolled, including 27 (3.3%) restricted type, 51 (6.3%) dilated type, 30 (3.7%) reduced ejection fraction type and 707 (86.7%) common type. A total of 704 out of 815 patients underwent genetic testing. Among them, 299 (42.5%) patients carried at least 1 sarcomere gene mutation. MYBPC3 and MYH7 mutation accounted for 42.1% (126/299) and 35.8% (107/299) respectively. 66.7% (16/24) of the patients with restricted type carried sarcomere gene mutation, which was higher than that in patients with dilated type (36.4% (16/44)) and in common type (41.5% (250/602), P=0.015). Among the patients with reduced ejection fraction, 56.7% (17/30) patients carried sarcomere gene mutations, 23.3% (7/30) carried multiple sarcomere mutations, which was higher than that in restricted type (8.3% (2/24)), in dilated type (9.1% (4/44)) and in common type 4.2% ((24/577), P<0.001). MYH7 and MYBPC3 were the main mutation gene types of all clinical subtypes, and the genotypes were similar among groups (all P>0.05). Seven hundred and three out 815 patients were followed up for 2.9 (1.4, 4.0) years. There were 53(7.5%) cardiovascular death. Cardiovascular death occurred in 5.0% (29/578) patients with common type, 13.0% (3/23) patients with restricted type, 16.3% (7/43) patients with dilated type and 46.7% (14/30) patients with decreased ejection fraction. Univariate Cox proportional hazards model analysis showed that the risk of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type was higher than that in patients with common type (P<0.001). After adjusting for gender, age of onset, body mass index, history of hypertension, coronary heart disease and diabetes, multivariate Cox proportional hazards model analysis showed that the HR of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type were 5.454 (95%CI 1.137-26.157, P=0.034) and 6.597 (95%CI 1.632-26.667, P=0.008) and 9.028 (95%CI 2.201-37.039, P=0.002) respectively, as compared to patients with common type. Conclusions: Most of the patients with non-obstructive HCM are common type, featured by mild clinical manifestations and good prognosis. Although the proportion of restricted type and dilated type is relatively low, and cardiac systolic function is mostly preserved, the clinical phenotype and prognosis of these patients are similarly severe and poor as patients with reduced ejection fraction. The genotypes are similar in different clinical subtypes, but the proportion of patients with sarcomere gene mutation is higher in restricted type, and the proportion of patients with multiple sarcomere gene mutation is higher in decreased ejection fraction type.


Assuntos
Cardiomiopatia Hipertrófica , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/genética , Estudos de Coortes , Humanos , Mutação , Fenótipo , Sarcômeros/genética
17.
Med Hypotheses ; 152: 110614, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34087614

RESUMO

Since Nixon famously declared war on cancer in 1971, trillions of dollars have been spent on cancer research but the life expectancy for most forms of cancer is still poor. There are many reasons for the partial success of cancer translational research. One of these can be the predominance of certain paradigms that potentially narrowed the vision in interpreting cancer. The main paradigm to explain carcinogenesis is based on DNA mutations, which is well interpreted by the somatic mutation theory (SMT). However, a different theory claims that cancer is instead a tissue disease as proposed by the Tissue Organization Field Theory (TOFT). Here, we propose new hypotheses to explain the origin and pathogenesis of cancer. In this perspective, the systemic-evolutionary theory of cancer (SETOC) is discussed as well as how the microenvironment affects the adaptation of transformed cells and the reversion to a unicellular-like or embryo-like phenotype.


Assuntos
Neoplasias , Evolução Biológica , Carcinogênese , Humanos , Mutação , Fenótipo , Microambiente Tumoral
18.
BMJ Open ; 11(6): e047356, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127492

RESUMO

OBJECTIVES: Using free-text clinical notes and reports from hospitalised patients, determine the performance of natural language processing (NLP) ascertainment of Framingham heart failure (HF) criteria and phenotype. STUDY DESIGN: A retrospective observational study design of patients hospitalised in 2015 from four hospitals participating in the Atherosclerosis Risk in Communities (ARIC) study was used to determine NLP performance in the ascertainment of Framingham HF criteria and phenotype. SETTING: Four ARIC study hospitals, each representing an ARIC study region in the USA. PARTICIPANTS: A stratified random sample of hospitalisations identified using a broad range of International Classification of Disease, ninth revision, diagnostic codes indicative of an HF event and occurring during 2015 was drawn for this study. A randomly selected set of 394 hospitalisations was used as the derivation dataset and 406 hospitalisations was used as the validation dataset. INTERVENTION: Use of NLP on free-text clinical notes and reports to ascertain Framingham HF criteria and phenotype. PRIMARY AND SECONDARY OUTCOME MEASURES: NLP performance as measured by sensitivity, specificity, positive-predictive value (PPV) and agreement in ascertainment of Framingham HF criteria and phenotype. Manual medical record review by trained ARIC abstractors was used as the reference standard. RESULTS: Overall, performance of NLP ascertainment of Framingham HF phenotype in the validation dataset was good, with 78.8%, 81.7%, 84.4% and 80.0% for sensitivity, specificity, PPV and agreement, respectively. CONCLUSIONS: By decreasing the need for manual chart review, our results on the use of NLP to ascertain Framingham HF phenotype from free-text electronic health record data suggest that validated NLP technology holds the potential for significantly improving the feasibility and efficiency of conducting large-scale epidemiologic surveillance of HF prevalence and incidence.


Assuntos
Aterosclerose , Insuficiência Cardíaca , Algoritmos , Aterosclerose/epidemiologia , Registros Eletrônicos de Saúde , Insuficiência Cardíaca/epidemiologia , Humanos , Pacientes Internados , Processamento de Linguagem Natural , Fenótipo
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 41(5): 789-792, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-34134969

RESUMO

OBJECTIVE: To investigate the pathogenic gene in a child with optic atrophy and analyze the influence of this gene mutation on protein structure. OBJECTIVE: We collected the clinical record of the 13-year-old girl and her relatives. The child received examinations of the visual acuity, visual field, fundus, OCT, visual-evoked potential (VEP) and the nerve system, underwent brain MRI and was followed up for 1 year. Genomic DNA was extracted from the peripheral blood of the child and her parents for next-generation sequencing of the whole exon. The pathogenic gene mutation was identified and the resultant changes in the protein structure was analyzed. OBJECTIVE: The patient presented with impaired vision and optic nerve atrophy in both eyes with low amplitude of VEP, but did not show dystonia or pyramidal tract symptom. Brain MRI detected no leukodystrophy. Genetic analysis suggested a heterozygous c.53_54delTG mutation in exon 1 in the NDUFV1 gene of complex I, which caused a frameshift starting with the codon valine 18, thus changing the amino acid to an Alanine residue and creating a premature stop codon at position 20 of the new reading frame (p.Val18AlafsX20). A heterozygous for c.1162+4A>C: IVS8 + 4A>C in intron 8 was also found. Protein structure analysis showed the missing of important structure of NDUFV1 subunit in complex I. OBJECTIVE: We identified a novel NDUFV1 mutation in a child with optic nerve atrophy. This finding may provide further insight into the genotype-phenotype correlations for NDUFV1 gene.


Assuntos
Atrofia Óptica , Adolescente , Atrofia/patologia , Criança , Complexo I de Transporte de Elétrons , Feminino , Mutação da Fase de Leitura , Humanos , Mutação , Atrofia Óptica/genética , Atrofia Óptica/patologia , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/patologia , Fenótipo
20.
Planta ; 254(1): 3, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34117927

RESUMO

MAIN CONCLUSION: Principal component and meta-QTL analyses identified genetic loci affecting the trade-off of wheat grain number and size, which could provide opportunities to optimize local breeding strategies for further yield improvement. Grain yield of wheat is complex, and its physiological and genetic bases remain largely unknown. Using the Forno/Oberkulmer recombinant inbred lines, this study validated the negative phenotypic relationships between thousand grain weight (TGW) and grain number components. This trade-off might be alleviated at the population level by early anthesis and at the shoot level by higher shoot biomass. Principal component (PC) analysis revealed three useful PCs, of which both PC1 and PC3 were positively associated with grain yield and grains m-2 through increased spikes m-2 (for PC1) or grains per spike (for PC3), while PC2 primarily reflected the trade-off of grain number and TGW. Quantitative trait locus (QTL) mapping detected eight and seven loci for PC1 and PC2, respectively, on chromosomes 1D, 2A, 3A, 3B, 4A, 4B, 5A and 7B, individually explaining 11.7‒29.3% of phenotypic variations. Using the 1203 QTLs published previously, a meta-analysis was performed to reveal 12, 21, 37 and 54 genomic regions (MQTLs) affecting grains m-2, spikes m-2, grains per spike and TGW, respectively. Moreover, 67 MQTLs (96%) for grain number were coincided with the TGW MQTLs, with reverse phenotypic effects, suggesting intensive genetic trade-off between grain number and size. The AGP2 gene, which encodes ADP-glucose pyrophosphorylase determining TGW, was found by haplotype analysis in the Forno/Oberkulmer population to affect grain number oppositely, indicating this trade-off at the gene level. Appropriate combinations of the QTLs/genes for local breeding targets, such as higher grain number or larger grains, therefore, would be critical to achieve future yield gains.


Assuntos
Melhoramento Vegetal , Triticum , Mapeamento Cromossômico , Grão Comestível/genética , Fenótipo , Locos de Características Quantitativas/genética , Triticum/genética
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