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1.
Nature ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143210

RESUMO

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared with its wild ancestors, modern bread wheat shows lower genetic diversity, caused by polyploidisation, domestication and breeding bottlenecks1,2. Wild wheat relatives represent genetic reservoirs, and harbour diversity and beneficial alleles that have not been incorporated into bread wheat. Here we establish and analyse extensive genome resources for Tausch's goatgrass (Aegilops tauschii), the donor of the bread wheat D genome. Our analysis of 46 Ae. tauschii genomes enabled us to clone a disease resistance gene and perform haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, which involves contributions from genetically and geographically discrete Ae. tauschii subpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement.

2.
Plant Biotechnol J ; 21(10): 1990-2001, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37589238

RESUMO

Plant breeding is constrained by trade-offs among different agronomic traits by the pleiotropic nature of many genes. Genes that contribute to two or more favourable traits with no penalty on yield are rarely reported, especially in wheat. Here, we describe the editing of a wheat auxin response factor TaARF12 by using CRISPR/Cas9 that rendered shorter plant height with larger spikes. Changes in plant architecture enhanced grain number per spike up to 14.7% with significantly higher thousand-grain weight and up to 11.1% of yield increase under field trials. Weighted Gene Co-Expression Network Analysis (WGCNA) of spatial-temporal transcriptome profiles revealed two hub genes: RhtL1, a DELLA domain-free Rht-1 paralog, which was up-regulated in peduncle, and TaNGR5, an organ size regulator that was up-regulated in rachis, in taarf12 plants. The up-regulation of RhtL1 in peduncle suggested the repression of GA signalling, whereas up-regulation of TaNGR5 in spike may promote GA response, a working model supported by differential expression patterns of GA biogenesis genes in the two tissues. Thus, TaARF12 complemented plant height reduction with larger spikes that gave higher grain yield. Manipulation of TaARF12 may represent a new strategy in trait pyramiding for yield improvement in wheat.


Assuntos
Edição de Genes , Triticum , Triticum/genética , Giberelinas , Melhoramento Vegetal , Agricultura , Grão Comestível/genética
3.
Plant J ; 108(6): 1754-1767, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34643010

RESUMO

Auxin signaling is essential for the development of grain size and grain weight, two important components for crop yield. However, no auxin/indole acetic acid repressor (Aux/IAA) has been functionally characterized to be involved in the development of wheat (Triticum aestivum L.) grains to date. Here, we identified a wheat Aux/IAA gene, TaIAA21, and studied its regulatory pathway. We found that TaIAA21 mutation significantly increased grain length, grain width, and grain weight. Cross-sections of mutant grains revealed elongated outer pericarp cells compared to those of the wild type, where the expression of TaIAA21 was detected by in situ hybridization. Screening of auxin response factor (ARF) genes highly expressed in early developing grains revealed that TaARF25 interacts with TaIAA21. In contrast, mutation of the tetraploid wheat (Triticum turgidum) ARF25 gene significantly reduced grain size and weight. RNA sequencing analysis revealed upregulation of several ethylene response factor genes (ERFs) in taiaa21 mutants which carried auxin response cis-elements in their promoter. One of them, ERF3, was upregulated in the taiaa21 mutant and downregulated in the ttarf25 mutant. Transactivation assays showed that ARF25 promotes ERF3 transcription, while mutation of TtERF3 resulted in reduced grain size and weight. Analysis of natural variations identified three TaIAA21-A haplotypes with increased allele frequencies in cultivars relative to landraces, a signature of breeding selection. Our work demonstrates that TaIAA21 works as a negative regulator of grain size and weight development via the ARF25-ERFs module and is useful for yield improvement in wheat.


Assuntos
Proteínas de Plantas/genética , Sementes/crescimento & desenvolvimento , Sementes/genética , Triticum/genética , Regulação da Expressão Gênica de Plantas , Frequência do Gene , Variação Genética , Haplótipos , Mutação , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Mapas de Interação de Proteínas/genética , Análise de Sequência de RNA , Tetraploidia , Triticum/crescimento & desenvolvimento
4.
Plant Biotechnol J ; 20(1): 75-88, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487615

RESUMO

The AGAMOUS-LIKE6 (AGL6)-like genes are ancient MADS-box genes and are functionally studied in a few model plants. The knowledge of these genes in wheat remains limited. Here, by studying a 'double homoeolog mutant' of the AGL6 gene in tetraploid wheat, we showed that AGL6 was required for the development of all four whorls of floral organs with dosage-dependent effect on floret fertility. Yeast two-hybrid analyses detected interactions of AGL6 with all classes of MADS-box proteins in the ABCDE model for floral organ development. AGL6 was found to interact with several additional proteins, including the G protein ß and γ (DEP1) subunits. Analysis of the DEP1-B mutant showed a significant reduction in spikelet number per spike in tetraploid wheat, while overexpression of AGL6 in common wheat increased the spikelet number per spike and hence the grain number per spike. RNA-seq analysis identified the regulation of several meristem activity genes by AGL6, such as FUL2 and TaMADS55. Our work therefore extensively updated the wheat ABCDE model and proposed an alternative approach to improve wheat grain yield by manipulating the AGL6 gene.


Assuntos
Proteínas de Domínio MADS , Triticum , Flores , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Meristema , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Triticum/metabolismo
5.
New Phytol ; 233(6): 2405-2414, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35015909

RESUMO

Reactive oxygen species (ROS) play important roles during anther and pollen development. DNA damage may cause chromosome fragmentation that is considered to underlie chromosome elimination for haploid induction by matrilineal pollen, a key step in MATRILINEAL-based double haploid breeding technology. But when and how DNA damage occurs is unknown. We performed comparative studies of wheat pollens from the wild-type and the CRISPR/Cas9 edited matrilineal mutant (mMTL). Chemical assays detected a second wave of ROS in mMTL pollen at the three-nuclei-stage and subsequently, along with reduced antioxidant enzyme activities. RNA-seq analysis revealed disturbed expression of genes for fatty acid biosynthesis and ROS homoeostasis. Gas chromatography-mass spectrometry measurement identified abnormal fatty acid metabolism that may contribute to defective mMTL pollen walls as observed using electron microscopy, consistent with the function of MTL as a phospholipase. Moreover, DNA damage was identified using TdT-mediated dUTP nick-end labelling and quantified using comet assays. Velocity patterns showed that ROS increments preceded that of DNA damage over the course of pollen maturation. Our work hypothesises that mMTL-triggered later-stage-specific ROS causes DNA damage that may contribute to chromosome fragmentation and hence chromosome elimination during haploid induction. These findings may provide more ways to accelerate double haploid-based plant breeding.


Assuntos
Melhoramento Vegetal , Triticum , Regulação da Expressão Gênica de Plantas , Haploidia , Pólen/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Triticum/metabolismo
6.
Anal Bioanal Chem ; 414(17): 5009-5022, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35641641

RESUMO

In this study, a fluorescent reagent, 4-((aminooxy)methyl)-7-hydroxycoumarin (AOHC), was for the first time applied to label the low-molecular-mass aldehydes (LMMAs) through reductive oxyamination reaction to afford single N,O-substituted oxyamine derivatives at room temperatures with derivatization efficiencies as high as 96.8%. In the following high-performance liquid chromatography with fluorescence detection analysis, 12 LMMAs, including furfurals, aromatic aldehydes, and aliphatic aldehydes, were baseline-separated on an ODS column and detected with low limits of detection (LODs) (0.2-50 nM), and good precisions (intraday relative standard deviations [RSDs] were 2.40-4.68%, and interday RSDs were 4.65-8.91%). This approach was then adopted to analyze six alcoholic beverages and five dairy products, and nine LMMAs with concentrations in the 0.28-798.16 µM range were successfully detected with excellent accuracies (recoveries were 92.2-106.2%). Finally, the results were statistically analyzed and discussed. The proposed method has several advantages, including high sensitivity, room-temperature labeling, and the avoidance of further extraction and/or enrichment procedures, demonstrating its great utility for monitoring LMMAs in various complex matrices.


Assuntos
Aldeídos , Bebidas , Aldeídos/análise , Bebidas/análise , Cromatografia Líquida de Alta Pressão/métodos , Hidroxilamina , Hidroxilaminas/análise , Indicadores e Reagentes
7.
Heart Surg Forum ; 25(3): E340-E344, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35787757

RESUMO

Left subclavian artery esophageal fistula usually occurs after esophageal cancer surgery, which is a rare complication, and it is even rarer after stent implantation of left subclavian artery pseudo-aneurysm. This paper reports the case of a 21-year-old male patient with left subclavian artery pseudo-aneurysm. Two-plus months after stent implantation, he stopped anticoagulant and antiplatelet drugs and developed pain in his left upper limb. The patient was diagnosed with arterial fistula. He was discharged from the hospital successfully after several operations, such as thoracic aortic stent implantation, left common carotid artery left axillary artery artificial vascular bypass. Conclusion: Early diagnosis and positive treatment lead to a good prognosis for patients with esophageal left subclavian artery fistula.


Assuntos
Aneurisma , Fístula Esofágica , Corpos Estranhos , Adulto , Aneurisma/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Fístula Esofágica/diagnóstico , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Corpos Estranhos/complicações , Humanos , Masculino , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , Adulto Jovem
8.
Int J Mol Sci ; 23(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35628397

RESUMO

Diversity surveys of germplasm are important for gaining insight into the genomic basis for crop improvement; especially InDels, which are poorly understood in hexaploid common wheat. Here, we describe a map of 89,923 InDels from exome sequencing of 262 accessions of a Chinese wheat mini-core collection. Population structure analysis, principal component analysis and selective sweep analysis between landraces and cultivars were performed. Further genome-wide association study (GWAS) identified five QTL (Quantitative Trait Loci) that were associated with spike length, two of them, on chromosomes 2B and 6A, were detected in 10 phenotypic data sets. Assisted with RNA-seq data, we identified 14 and 21 genes, respectively that expressed in spike and rachis within the two QTL regions that can be further investigated for candidate genes discovery. Moreover, InDels were found to be associated with awn length on chromosomes 5A, 6B and 4A, which overlapped with previously reported genetic loci B1 (Tipped 1), B2 (Tipped 2) and Hd (Hooded). One of the genes TaAGL6 that was previously shown to affect floral organ development was found at the B2 locus to affect awn length development. Our study shows that trait-associated InDels may contribute to wheat improvement and may be valuable molecular markers for future wheat breeding.


Assuntos
Estudo de Associação Genômica Ampla , Triticum , China , Melhoramento Vegetal , Locos de Características Quantitativas , Triticum/genética
9.
Plant Foods Hum Nutr ; 77(2): 172-180, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35449430

RESUMO

Inflammation is a contributing factor to the initiation and progression of many diseases, and some food-derived biofunctional peptides show high anti-inflammatory activity. In our previous study, we demonstrated that peptides derived from trypsin hydrolysis of rice protein show good immunological activity. In the present study, proteins of broken rice were extracted and identified by macroporous resin fractionation and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Subsequently, a bioinformatics prediction and in silico simulation approach was used to screen for peptides showing anti-inflammatory activity, including inhibition of the production of nitric oxide and proinflammatory cytokines (interleukin-1ß, interleukin-6, and tumor necrosis factor-α) by lipopolysaccharide-stimulated RAW264.7 mice macrophages. Three peptides (DNIQGITKPAIR, IAFKTNPNSMVSHIAGK, and IGVAMDYSASSKR) that demonstrated the highest binding affinity were synthesized, and their in vitro anti-inflammatory activity was investigated. This is the first study that integrates LC-MS/MS identification and bioinformatics prediction for reporting the anti-inflammatory activity of anti-inflammatory peptides derived from broken rice protein. The study findings revealed that the peptides derived from the byproduct of rice milling could be potentially used as natural anti-inflammatory alternativities.


Assuntos
Oryza , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cromatografia Líquida , Citocinas/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Células RAW 264.7 , Espectrometria de Massas em Tandem
10.
Plant J ; 102(2): 299-310, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31778224

RESUMO

The wheat AP2-like transcription factor gene Q has played a major role in domestication by conferring the free-threshing character and pleiotropically affecting numerous other traits. However, little information is known regarding the molecular mechanisms associated with the regulation of these traits by Q, especially for the structural determination of threshability. Here, transcriptome analysis of immature spike tissues in three lines nearly isogenic for Q revealed over 3000 differentially expressed genes (DEGs) involved in a number of pathways. Using phenotypic, microscopic, transcriptomic, and tissue-specific gene expression analyses, we demonstrated that Q governs threshability through extensive modification of wheat glumes including their structure, cell wall thickness, and chemical composition. Critical DEGs and pathways involved in secondary cell wall synthesis and regulation of the chemical composition of glumes were identified. We also showed that the mutation giving rise to the Q allele synchronized the expression of genes for micro-sporogenesis that affected pollen fertility, and may determine the final grain number for wheat spikes. Transcriptome dissection of genes and genetic pathways regulated by Q should further our understanding of wheat domestication and improvement.


Assuntos
Fatores de Transcrição/genética , Transcriptoma , Triticum/genética , Alelos , Domesticação , Grão Comestível , Fertilidade/genética , Perfilação da Expressão Gênica , Mutação , Especificidade de Órgãos , Fenótipo , Proteínas de Plantas/genética , Pólen/genética
11.
Acta Pharmacol Sin ; 42(10): 1610-1619, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33495514

RESUMO

Septic acute liver injury is one of the leading causes of fatalities in patients with sepsis. Toll-like receptor 4 (TLR4) plays a vital role in response to lipopolysaccharide (LPS) challenge, but the mechanisms underlying TLR4 function in septic injury remains unclear. In this study, we investigated the role of TLR4 in LPS-induced acute liver injury (ALI) in mice with a focus on inflammation and apoptosis. Wild-type (WT) and TLR4-knockout (TLR4-/-) mice were challenged with LPS (4 mg/kg) for 6 h. TLR4 signaling cascade markers (TLR4, MyD88, and NF-κB), inflammatory markers (TNFα, IL-1ß, and IL-6), and apoptotic markers (Bax, Bcl-2, and caspase 3) were evaluated. We showed that LPS challenge markedly increased the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and other liver pathological changes in WT mice. In addition, LPS challenge elevated the levels of liver carbonyl proteins and serum inflammatory cytokines, upregulated the expression of TLR4, MyD88, and phosphorylated NF-κB in liver tissues. Moreover, LPS challenge significantly increased hepatocyte apoptosis, caspase 3 activity, and Bax level while suppressing Bcl-2 expression in liver tissues. These pathological changes were greatly attenuated in TLR4-/- mice. Similar pathological responses were provoked in primary hepatic Kupffer cells isolated from WT and TLR4-/- mice following LPS (1 µg/mL, 6 h) challenge. In summary, these results demonstrate that silencing of TLR4 attenuates LPS-induced liver injury through inhibition of inflammation and apoptosis via TLR4/MyD88/NF-κB signaling pathway. TLR4 deletion confers hepatoprotection against ALI induced by LPS, possibly by repressing macrophage inflammation and apoptosis.


Assuntos
Apoptose/fisiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Inflamação/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Caspase 3/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/metabolismo , Técnicas de Inativação de Genes , Hepatócitos/metabolismo , Células de Kupffer/metabolismo , Lipopolissacarídeos , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/genética
12.
Heart Surg Forum ; 24(2): E317-E319, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798044

RESUMO

Epistaxis is a common emergency, and its main causes are hypertensive crisis and trauma. Nasal packing is the primary treatment. After active symptomatic treatment, the symptoms of epistaxis effectively can be controlled. In this case report, the patient was treated with epistaxis many times in the outpatient department. After nasal examination, there was a clear bleeding point, and it was treated with gauze packing or silver nitrate cauterization. The symptoms of epistaxis gradually got worse and was accompanied with fever and progressive anemia. After blood culture and color Doppler ultrasound examination, it was confirmed that it was endocarditis caused by defective hypoxic bacterial infection. After active antibacterial and surgical treatment, the symptoms of epistaxis, fever and anemia were relieved.


Assuntos
Endocardite/complicações , Epistaxe/complicações , Antibacterianos/uso terapêutico , Ascomicetos , Ecocardiografia Doppler em Cores , Endocardite/diagnóstico , Endocardite/tratamento farmacológico , Epistaxe/diagnóstico , Humanos , Masculino , Adulto Jovem
13.
Mikrochim Acta ; 188(12): 421, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787714

RESUMO

A Fe3O4/mesoporous graphitized carbon (Fe3O4/m-GC) composite was prepared through a facile calcination method with iron-based metal-organic frameworks (Fe-MOFs) as a sacrificial template. After carbonization, the Fe3O4 nanoparticles were uniformly dispersed in the mesoporous carbon support, resulting in spatial structural stability. The mesoporous carbon support obtained was highly graphitized and exhibited eminent electrical conductivity, which accelerated the electron transfer between the Fe3O4 nanoparticles by Fe(II)/Fe(III) redox cycles and m-GC by C = Csp2/C-Csp3 redox cycles, leading to the excellent peroxidase-mimetic activity of Fe3O4/m-GC. Km values for tetramethylbenzidine (TMB) and H2O2 were 26.8 and 15.8 times lower than that of natural horseradish peroxidase, respectively. Taking advantage of the peroxidase-mimetic activity of Fe3O4/m-GC, a colorimetric assay was fabricated for detecting glucose in the range 0.5 ~ 200 µM, with a limit of detection of 0.24 µM. Fig 1 A Schematic illustration of the preparation process of Fe3O4/m-GC, B schematic illustration of a proposed synergistic catalytic mechanism of TMB oxidation by Fe3O4/m-GC.


Assuntos
Técnicas Biossensoriais/métodos , Carbono/química , Óxido Ferroso-Férrico/química , Glucose/química , Peroxidase/química
14.
Biochem Biophys Res Commun ; 533(3): 565-572, 2020 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-32981678

RESUMO

A growing number of studies have revealed that long noncoding RNAs (lncRNAs) can function as important oncogenes or tumor suppressors. This study aimed to investigate the regulatory role of lncRNA DNAH17 antisense RNA 1 (DNAH17-AS1) on non-small cell lung cancer (NSCLC) and the underlying molecular mechanisms. We observed that the expression of DNAH17-AS1 and CCNA2 mRNA was distinctly upregulated in NSCLC specimens and cell lines, while miR-877-5p expression was significantly decreased. DNAH17-AS1 could be used to distinguish NSCLC specimens from adjacent non-tumor tissues. Clinical assays revealed that high DNAH17-AS1 was associated with TNM stage, distant metastasis and shorter overall survival and disease-free survival. Functional assays indicated that knockdown of DNAH17-AS1 suppressed the proliferation, migration and invasion of H1299 and 95D cells, and promoted apoptosis. Mechanically, DNAH17-AS1 served as competing endogenous RNA (ceRNA) for miR-877-5p to positively recover CCNA2. Overall, we identified a novel NSCLC-related lncRNA, DNAH17-AS1 which may exert an oncogenic function via serving as a sponge for miR-877-5p to upregulate CCNA2. Our study presents novel insights into NSCLC progression and provided a prospective therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Ciclina A2/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinogênese , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Movimento Celular , Proliferação de Células , Ciclina A2/metabolismo , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Prognóstico
15.
BMC Plant Biol ; 20(1): 97, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131739

RESUMO

BACKGROUND: In contrast to most animal species, polyploid plant species are quite tolerant of aneuploidy. Here, the global transcriptome of four aneuploid derivatives of a synthetic hexaploid wheat line was acquired, with the goal of characterizing the relationship between gene copy number and transcript abundance. RESULTS: For most of the genes mapped to the chromosome involved in aneuploidy, the abundance of transcripts reflected the gene copy number. Aneuploidy had a greater effect on the strength of transcription of genes mapped to the chromosome present in a noneuploid dose than on that of genes mapped elsewhere in the genome. Overall, changing the copy number of one member of a homeologous set had little effect on the abundance of transcripts generated from the set of homeologs as a whole, consistent with the tolerance of aneuploidy exhibited by allopolyploids, whether in the form of a chromosomal deficit (monosomy) or chromosomal excess (trisomy). CONCLUSIONS: Our findings shed new light on the genetic regulation of homeoallele transcription and contribute to a deeper understanding of allopolyploid genome evolution, with implications for the breeding of polyploid crops.


Assuntos
Aneuploidia , Poliploidia , Transcriptoma , Triticum/genética , Dosagem de Genes
16.
Plant Biotechnol J ; 18(3): 732-742, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31471988

RESUMO

Wheat is one of the most important staple crops worldwide and also an excellent model species for crop evolution and polyploidization studies. The breakthrough of sequencing the bread wheat genome and progenitor genomes lays the foundation to decipher the complexity of wheat origin and evolutionary process as well as the genetic consequences of polyploidization. In this study, we sequenced 3286 BACs from chromosome 7DL of bread wheat cv. Chinese Spring and integrated the unmapped contigs from IWGSC v1 and available PacBio sequences to close gaps present in the 7DL assembly. In total, 8043 out of 12 825 gaps, representing 3 491 264 bp, were closed. We then used the improved assembly of 7DL to perform comparative genomic analysis of bread wheat (Ta7DL) and its D donor, Aegilops tauschii (At7DL), to identify domestication signatures. Results showed a strong syntenic relationship between Ta7DL and At7DL, although some small rearrangements were detected at the distal regions. A total of 53 genes appear to be lost genes during wheat polyploidization, with 23% (12 genes) as RGA (disease resistance gene analogue). Furthermore, 86 positively selected genes (PSGs) were identified, considered to be domestication-related candidates. Finally, overlapping of QTLs obtained from GWAS analysis and PSGs indicated that TraesCS7D02G321000 may be one of the domestication genes involved in grain morphology. This study provides comparative information on the sequence, structure and organization between bread wheat and Ae. tauschii from the perspective of the 7DL chromosome, which contribute to better understanding of the evolution of wheat, and supports wheat crop improvement.


Assuntos
Evolução Biológica , Cromossomos de Plantas/genética , Genoma de Planta , Triticum/genética , Aegilops/genética , Hibridização Genômica Comparativa , Locos de Características Quantitativas , Sintenia
17.
Pharmacol Res ; 161: 105129, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32783976

RESUMO

Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer. However, there has been little improvement in its cure rate in the last 30 years, due to its intricate heterogeneity and drug resistance. Accumulating evidences have demonstrated that dysregulation of calcium (Ca2+) homeostasis contributes to oncogenesis and promotes tumor development. Inhibitors of Ca2+ channels/transporters to restore intracellular Ca2+ level were found to arrest tumor cell division, induce apoptosis, and suppress tumor growth both in vitro and in vivo. Dolutegravir (DTG), which is a first-line drug for Acquired Immune Deficiency Syndrome (AIDs) treatment, has been shown to increase intracellular Ca2+ levels and Reactive oxygen species (ROS) levels in human erythrocytes, leading to suicidal erythrocyte death or eryptosis. To explore the potential of DTG as an antitumor agent, we have designed and synthesized a panel of compounds based on the principle of biologically active substructure splicing of DTG. Our data demonstrated that 7-methoxy-4-methyl-6,8-dioxo-N-(3-(1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)phenyl)-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide (DTHP), a novel derivative of DTG, strongly inhibited the colony-forming ability and proliferation of NSCLC cells, but displayed no cytotoxicity to normal lung cells. DTHP treatment also induced apoptosis and upregulate intracellular Ca2+ level in NSCLC cells significantly. Inhibiting Ca2+ signaling alleviated DTHP-induced apoptosis, suggesting the perturbation of intracellular Ca2+ is responsible for DTHP-induced apoptosis. We further discovered that DTHP activates AMPK signaling pathway through binding to SERCA, a Ca2+-ATPase. On the other hand, DTHP treatment promoted mitochondrial ROS production, causing mitochondrial dysfunction and cell death. Finally, DTHP effectively inhibited tumor growth in the mouse xenograft model of lung cancer with low toxicity to normal organs. Taken together, our work identified DTHP as a superior antitumor agent, which will provide a novel strategy for the treatment of NSCLC with potential clinical application.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Oxazinas/farmacologia , Piperazinas/farmacologia , Piridonas/farmacologia , Células A549 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Geriatr Psychiatry Neurol ; 33(5): 272-281, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31645180

RESUMO

The current study aimed to investigate the effects of group reminiscence therapy on cognitive function, depression, neuropsychiatric symptoms, and activities of daily living in patients with mild-to-moderate Alzheimer disease (AD). A single-blind randomized parallel-design controlled trial was conducted between May 1, 2017, and April 30, 2018. Ninety patients with mild-to-moderate AD recruited from Beijing Geriatric Hospital were randomly allocated into intervention (n = 45) and control groups (n = 45). In the intervention group, group-based reminiscence therapy was performed in two 30- to 45-minute sessions weekly for 12 weeks. Control participants received only conventional drug treatments and routine daily care. Alzheimer disease-related symptoms were evaluated using the Alzheimer's Disease Assessment Scale-Cognitive section, the Cornell Scale for Depression in Dementia (CSDD), the Neuropsychiatric Inventory, and the Barthel Index. Four time points were set for data collection: baseline (before treatment), 4 weeks (during treatment), 12 weeks (end of treatment), and 24 weeks (12 weeks posttreatment). χ2 Tests, independent t tests, repeated-measures analysis of variance, and Bonferroni tests were used for data analysis. Significant improvements in depressive and neuropsychiatric symptoms were found in the intervention group compared to the control group (P < .05). Mean CSDD scores in the intervention group were improved at all 3 time points compared to baseline and showed the greatest effect at 12 weeks (t = 2.076, P = .041) and 24 weeks follow-up (t = 3.834, P = .000) compared to controls. Group reminiscence therapy was effective for improving depressive symptoms and was beneficial for treating neuropsychiatric symptoms in patients with AD.


Assuntos
Atividades Cotidianas/psicologia , Doença de Alzheimer/psicologia , Cognição/fisiologia , Depressão/terapia , Neuropsiquiatria/métodos , Idoso , Feminino , Humanos , Masculino , Método Simples-Cego , Resultado do Tratamento
19.
Int J Mol Sci ; 21(16)2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32823943

RESUMO

Porphyrins have planar and conjugated structures, good optical properties, and other special functional properties. Owing to these excellent properties, in recent years, porphyrins and their analogues have emerged as a multifunctional platform for chemical sensors. The rich chemistry of these molecules offers many possibilities for metal ions detection. This review mainly discusses two types of molecular porphyrin and porphyrin composite sensors for metal ions detection, because porphyrins can be functionalized to improve their functional properties, which can introduce more chemical and functional sites. According to the different application materials, the section of porphyrin composite sensors is divided into five sub-categories: (1) porphyrin film, (2) porphyrin metal complex, (3) metal-organic frameworks, (4) graphene materials, and (5) other materials, respectively.


Assuntos
Metais/química , Porfirinas/química , Corantes Fluorescentes/química , Íons , Estruturas Metalorgânicas/química , Sondas Moleculares/química
20.
New Phytol ; 221(2): 1023-1035, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30256420

RESUMO

DNA methylation is dynamically involved in plant immunity, but little information is known about its roles in plant interactions with biotrophic fungi, especially in temperate grasses such as wheat (Triticum aestivum). Using wheat diploid progenitor Aegilops tauschii accession AL8/78, the genome of which has been sequenced, we assessed the extent of DNA methylation in response to infection with Blumeria graminis f. sp. tritici (Bgt), which causes powdery mildew. Upon Bgt infection, ARGONAUTE4a (AGO4a) was significantly downregulated in A. tauschii, which was accompanied by a substantial reduction in AGO4a-sorted 24-nt siRNA levels, especially for genes near transposable elements (TAGs). Bisulfite sequencing revealed abundant differentially methylated regions (DMRs) with CHH hypomethylation. TAGs bearing CHH-hypomethylated DMRs were enriched for 'response to stress' functions, including receptor kinase, peroxidase, and pathogenesis-related genes. Virus-induced gene silencing (VIGS) of a DOMAINS REARRANGED METHYLASE 2 (DRM2) homolog enhanced plant resistance to Bgt. The effect of CHH hypomethylation was exemplified by the upregulation of a pathogenesis-related ß-1,3-glucanse gene implicated in Bgt defense. These findings support the idea that dynamic DNA methylation represents a regulatory layer in the complex mechanism of plant immunity, which could be exploited to improve disease resistance in common wheat.


Assuntos
Aegilops/genética , Ascomicetos/fisiologia , Metilação de DNA , Resistência à Doença , Doenças das Plantas/microbiologia , Proteínas de Plantas/metabolismo , Aegilops/imunologia , Aegilops/microbiologia , Interações Hospedeiro-Patógeno , Proteínas de Plantas/genética , Triticum/genética
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