Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 105
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Elife ; 92020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207684

RESUMO

Carbon catabolite repression 4 (CCR4) is a conserved mRNA deadenylase regulating posttranscriptional gene expression. However, regulation of CCR4 in virus infections is less understood. Here, we characterized a pro-viral role of CCR4 in replication of a plant cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV). The barley (Hordeum vulgare) CCR4 protein (HvCCR4) was identified to interact with the BYSMV phosphoprotein (P). The BYSMV P protein recruited HvCCR4 from processing bodies (PBs) into viroplasm-like bodies. Overexpression of HvCCR4 promoted BYSMV replication in plants. Conversely, knockdown of the small brown planthopper CCR4 inhibited viral accumulation in the insect vector. Biochemistry experiments revealed that HvCCR4 was recruited into N-RNA complexes by the BYSMV P protein and triggered turnover of N-bound cellular mRNAs, thereby releasing RNA-free N protein to bind viral genomic RNA for optimal viral replication. Our results demonstrate that the co-opted CCR4-mediated RNA decay facilitates cytorhabdovirus replication in plants and insects.

2.
J Autoimmun ; 106: 102349, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31629629

RESUMO

BACKGROUND: Genome-wide association studies have identified over 120 risk loci for psoriasis. However, most of the variations are located in non-coding region with high frequency and small effect size. Pathogenetic variants are rarely reported except HLA-C*0602 with the odds ratio being approximately 4.0 in Chinese population. Although rare variations still account for a small proportion of phenotypic variances in complex diseases, their effect on phenotypes is large. Recently, more and more studies focus on the low-frequency functional variants and have achieved a certain amount of success. METHOD: Whole genome sequencing and sanger sequencing was performed on 8 MZ twin pairs discordant for psoriasis to scan and verified the de novo mutations (DNMs). Additionally, 665 individuals with about 20 years' medical history versus 2054 healthy controls and two published large population studies which had about 8 years' medical history (including 10,727 cases versus 10,582 controls) were applied to validate the enrichment of rare damaging mutations in two DNMs genes. Besides, to verify the pathogenicity of candidate DNM in C3, RNA-sequencing for CD4+, CD8+ T cells of twins and lesion, non-lesion skin of psoriasis patients were carried out. Meanwhile, the enzyme-linked immunosorbent assay kit was used to detect the level of C3, C3b in the supernatant of peripheral blood. RESULT: A total of 27 DNMs between co-twins were identified. We found six of eight twins carry HLA-C∗0602 allele which have large effects on psoriasis. And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele. In the replication stage, we found 2 loss-of-function (LOF) variants of C3 only in 665 cases with about 20 years' medical history and gene-wise analysis in 665 cases and 2054 controls showed that the rare missense mutations in C3 were enriched in cases (OR = 1.91, P = 0.0028). We further scanned the LOF mutations of C3 in two published studies (about 8 years' medical history), and found one LOF mutation in the case without carrying HLA-C*0602. In the individual with DNM in C3, RNA sequencing showed the expression level of C3 in skin was significant higher than healthy samples in public database (TPM fold change = 1.40, P = 0.000181) and ELISA showed protein C3 in peripheral blood was higher (~2.2-fold difference) than the other samples of twins without DNM in C3. CONCLUSION: To the best of our knowledge, this is the first report that DNM in C3 is the likely pathological mutations, and it provided a better understanding of the genetic etiology of psoriasis and additional treatments for this disease.

3.
J Clin Invest ; 130(1): 438-450, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31815740

RESUMO

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

4.
J Med Microbiol ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31778109

RESUMO

Introduction. Ankylosing spondylitis (AS) is a systemic progressive disease with an unknown etiology that may be related to the gut microbiome. Therefore, a more thorough understanding of its pathogenesis is necessary for directing future therapy.Aim. We aimed to determine the differences in intestinal microbial composition between healthy individuals and patients with AS who received and who did not receive treatment interventions. In parallel, the pathology of AS in each patient was analysed to better understand the link between AS treatment and the intestinal microbiota of the patients.Methodology. Sixty-six faecal DNA samples, including 37 from healthy controls (HCs), 11 from patients with untreated AS (NM), 7 from patients treated with nonsteroidal anti-inflammatory drugs (e.g. celecoxib; WM) and 11 from patients treated with Chinese herbal medicine (CHM), such as the Bushen-Qiangdu-Zhilv decoction, were collected and used in the drug effect analysis. All samples were sequenced using Illumina HiSeq 4000 and the microbial composition was determined.Results. Four species were enriched in the patients with AS: Flavonifractor plautii, Oscillibacter, Parabacteroides distasonis and Bacteroides nordii (HC vs. NM, P<0.05); only F. plautii was found to be significantly changed in the NM-HC comparison. No additional species were found in the HC vs. CHM analysis, which indicated a beneficial effect of CHM in removing the other three strains. F. plautii was found to be significantly increased in the comparison between the HC and WM groups, along with four other species (Clostridium bolteae, Clostridiales bacterium 1_7_47FAA, C. asparagiforme and C. hathewayi). The patients with AS harboured more bacterial species associated with carbohydrate metabolism and glycan biosynthesis in their faeces. They also had bacterial profiles less able to biodegrade xenobiotics or synthesize and transport vitamins.Conclusion. The gut microbiota of the patients with AS varied from that of the HCs, and the treatment had an impact on this divergence. Our data provide insight that could guide improvements in AS treatment.

5.
PLoS Negl Trop Dis ; 13(11): e0007846, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31751335

RESUMO

Angiostrongylus cantonensis (rat lungworm) is the etiological agent of angiostrongyliasis, mainly causing eosinophilic meningitis or meningoencephalitis in human. Although the biology of A. cantonensis is relatively well known, little is understood about the mechanisms of the parasite's development and survival in definitive hosts, or its adaptation to a broad range of snail intermediate hosts. Here, we generate a high-quality assembly of a well-defined laboratory strain of A. cantonensis from Guangzhou, China, by using Illumina and PacBio sequencing technologies. We undertake comparative analyses with representative helminth genomes and explore transcriptomic data throughout key developmental life-cycles of the parasite. We find that part of retrotransposons and gene families undergo multiple waves of expansions. These include extracellular superoxide dismutase (EC-SOD) and astacin-like proteases which are considered to be associated with invasion and survival of the parasite. Furthermore, these paralogs from different sub-clades based on phylogeny, have different expression patterns in the molluscan and rodent stages, suggesting divergent functions under the different parasitic environment. We also find five candidate convergent signatures in the EC-SOD proteins from flukes and one sub-clade of A. cantonensis. Additionally, genes encoding proteolytic enzymes, involved in host hemoglobin digestion, exhibit expansion in A. cantonensis as well as two other blood-feeding nematodes. Overall, we find several potential adaptive evolutionary signatures in A. cantonensis, and also in some other helminths with similar traits. The genome and transcriptomes provide a useful resource for detailed studies of A. cantonensis-host adaptation and an in-depth understanding of the global-spread of angiostrongyliasis.


Assuntos
Adaptação Biológica , Angiostrongylus cantonensis/classificação , Angiostrongylus cantonensis/genética , Evolução Molecular , Genoma Helmíntico , Infecções por Strongylida/parasitologia , Infecções por Strongylida/veterinária , Angiostrongylus cantonensis/isolamento & purificação , Animais , China , Biologia Computacional , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Roedores , Trematódeos
6.
Chem Commun (Camb) ; 55(78): 11691-11694, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31508619

RESUMO

Ar&H2 plasma treatment was proposed to enhance the response of a p-CuAlO2 sensor toward volatile organic compounds. Comprehensive defect characterization studies indicate a substantial increase of surface unsaturated oxygen vacancy (VO) defects via plasma treatment, which could provide active sites for molecule adsorption and the subsequent interfacial redox reaction.

7.
Inorg Chem ; 58(15): 9974-9981, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31317742

RESUMO

Metal oxide semiconductor (MOS) gas sensors operated at room temperature (RT) hold great promise for environmental monitoring in the emerging smart society. An in-depth understanding of the gas/MOS interfacial charge exchange under the ambient moist atmosphere is essential for subsequent molecule recognition. Herein, delafossite p-CuScO2 with a unique oxygen intercalation property was utilized. Eight orders of resistance tuning could be rationally achieved via controlling oxygen intercalation realized by air annealing (without altering the size and morphological properties), which allows extraction of both the intrinsic (gas/MOS interaction, p-type response) and extrinsic (gas/H2O/MOS interaction, pseudo-n-type response) sensing mechanisms upon exposure to ammonia molecules. This work could provide an insight into the underlying sensing mechanism of RT sensors working in an ambient moist atmosphere, and the unique n- to p-type switching contains rich molecule related features that could be potentially explored for molecule recognition.

8.
Nat Plants ; 5(8): 810-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31308504

RESUMO

Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.

9.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31231774

RESUMO

Gram-negative bacterium Vibrio cholerae is the causative agent of cholera, a life-threatening diarrheal disease. During its infectious cycle, V. cholerae routinely switches niches between aquatic environment and host gastrointestinal tract, in which V. cholerae modulates its transcriptome pattern accordingly for better survival and proliferation. A comprehensive resource for V. cholerae transcriptome will be helpful for cholera research, including prevention, diagnosis and intervention strategies. In this study, we constructed a microarray and RNA-seq database of V. cholerae (Mr.Vc), containing gene transcriptional expression data of 145 experimental conditions of V. cholerae from various sources, covering 25 937 entries of differentially expressed genes. In addition, we collected relevant information including gene annotation, operons they may belong to and possible interaction partners of their protein products. With Mr.Vc, users can easily find transcriptome data they are interested in, such as the experimental conditions in which a gene of interest was differentially expressed in, or all genes that were differentially expressed in an experimental condition. We believe that Mr.Vc database is a comprehensive data repository dedicated to V. cholerae and could be a useful resource for all researchers in related fields. Mr.Vc is available for free at http://bioinfo.life.hust.edu.cn/mrvc.


Assuntos
Proteínas de Bactérias , Bases de Dados de Ácidos Nucleicos , Regulação Bacteriana da Expressão Gênica , RNA Bacteriano , Transcriptoma , Vibrio cholerae , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Perfilação da Expressão Gênica , Humanos , RNA Bacteriano/biossíntese , RNA Bacteriano/genética , Vibrio cholerae/genética , Vibrio cholerae/metabolismo
10.
New Phytol ; 223(4): 2120-2133, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31059138

RESUMO

Plant viruses have been used as rapid and cost-effective expression vectors for heterologous protein expression in genomic studies. However, delivering large or multiple foreign proteins in monocots and insect pests is challenging. Here, we recovered a recombinant plant cytorhabdovirus, Barley yellow striate mosaic virus (BYSMV), for use as a versatile expression platform in cereals and the small brown planthopper (SBPH, Laodelphax striatellus) insect vector. We engineered BYSMV vectors to provide versatile expression platforms for simultaneous expression of three foreign proteins in barley plants and SBPHs. Moreover, BYSMV vectors could express the c. 600-amino-acid ß-glucuronidase (GUS) protein and a red fluorescent protein stably in systemically infected leaves and roots of cereals, including wheat, barley, foxtail millet, and maize plants. Moreover, we have demonstrated that BYSMV vectors can be used in barley to analyze biological functions of gibberellic acid (GA) biosynthesis genes. In a major technical advance, BYSMV vectors were developed for simultaneous delivery of CRISPR/Cas9 nuclease and single guide RNAs for genomic editing in Nicotiana benthamiana leaves. Taken together, our results provide considerable potential for rapid screening of functional proteins in cereals and planthoppers, and an efficient approach for developing other insect-transmitted negative-strand RNA viruses.


Assuntos
Grão Comestível/genética , Grão Comestível/virologia , Genoma de Planta , Genômica , Hemípteros/virologia , Vírus de Plantas/fisiologia , Rhabdoviridae/fisiologia , Animais , Sequência de Bases , DNA Complementar/genética , Edição de Genes , Vetores Genéticos/metabolismo , Glucuronidase/metabolismo , Hordeum/ultraestrutura , Hordeum/virologia , Folhas de Planta/virologia , Vírus de Plantas/ultraestrutura , RNA Guia/metabolismo , Rhabdoviridae/ultraestrutura , Tabaco/ultraestrutura , Tabaco/virologia
11.
Nat Commun ; 10(1): 2037, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048690

RESUMO

Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer (GC) tumorigenesis. Here, we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC. Specifically, we nominate a novel hotspot involving the super-enhancer of ZFP36L2 presents in approximately 10% GCs from different cohorts, the oncogenic role of which is further confirmed by experimental data. In addition, our data reveal a mutational signature, specifically occurring in noncoding region, significantly enriched in tumors with cadherin 1 mutations, and associated with poor prognoses. Collectively, our data suggest that TDs might serve as an important mechanism for cancer gene activation and provide a novel signature for stratification.


Assuntos
Oncogenes/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Caderinas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos/genética , Éxons/genética , Feminino , Duplicação Gênica/genética , Variação Estrutural do Genoma , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estômago/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Sequenciamento Completo do Genoma
12.
J Exp Bot ; 70(15): 4049-4062, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020313

RESUMO

As obligate parasites, plant viruses usually hijack host cytoskeletons for replication and movement. Rhabdoviruses are enveloped, negative-stranded RNA viruses that infect vertebrates, invertebrates, and plants, but the mechanisms of intracellular trafficking of plant rhabdovirus proteins are largely unknown. Here, we used Barley yellow striate mosaic virus (BYSMV), a plant cytorhabdovirus, as a model to investigate the effects of the actin cytoskeleton on viral intracellular movement and viral RNA synthesis in a mini-replicon (MR) system. The BYSMV P protein forms mobile inclusion bodies that are trafficked along the actin/endoplasmic reticulum network, and recruit the N and L proteins into viroplasm-like structures. Deletion analysis showed that the N terminal region (aa 43-55) and the remaining region (aa 56-295) of BYSMV P are essential for the mobility and formation of inclusions, respectively. Overexpression of myosin XI-K tails completely abolishes the trafficking activity of P bodies, and is accompanied by a significant reduction of viral MR RNA synthesis. These results suggest that BYSMV P contributes to the formation and trafficking of viroplasm-like structures along the ER/actin network driven by myosin XI-K. Thus, rhabdovirus P appears to be a dynamic hub protein for efficient recruitment of viral proteins, thereby promoting viral RNA synthesis.

13.
Med Sci Monit ; 25: 2819-2834, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30994108

RESUMO

BACKGROUND The present study aimed to evaluate the difference in microbiota diversity in the oral cavity and fluid bronchoalveolar lavage (BALF) of patients with lung cancer. MATERIAL AND METHODS Buccal (saliva) and lower respiratory tract BALF samples were collected from 51 patients with primary bronchogenic carcinoma and 15 healthy controls, and bacterial genomic DNA was extracted. High-throughput 16S rDNA amplicon sequencing was performed, and microbial diversity, composition, and functions of microbiota were analyzed by bioinformatics methods. RESULTS Patients with lung cancer have lower microbial diversity than healthy controls in both saliva and BALF samples. Significant segregation was observed between the different pathological types of lung cancer groups and the control group regardless of the sampling site. Treponema and Filifactor were identified as potential bacterial biomarkers in BALF samples, while Filifactor was ideal to distinguish healthy controls from lung cancer patients. Moreover, the predictive variation analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway showed that the metabolic differences in microbiota varied by sampling site. CONCLUSIONS Lung cancer patients carry a different and less diverse microorganism community than healthy controls. Certain bacterial taxa might be associated with lung cancer, but the exact species depends on the sampling site and the pathological type. This study provides basic data on the microbiota diversity in BALF and saliva samples from lung cancer patients. Further investigation with a larger sample size should help validate the enriched species in different pathological types of lung cancers.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Carcinoma Broncogênico/microbiologia , Neoplasias Pulmonares/microbiologia , Saliva/microbiologia , Adulto , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Biomarcadores Tumorais/análise , Lavagem Broncoalveolar/métodos , Feminino , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Dados Preliminares
14.
Nat Commun ; 10(1): 1245, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30886153

RESUMO

The genetic landscape of clear cell renal cell carcinoma (ccRCC) had been investigated extensively but its evolution patterns remained unclear. Here we analyze the clonal architectures of 473 patients from three different populations. We find that the mutational signatures vary substantially across different populations and evolution stages. The evolution patterns of ccRCC have great inter-patient heterogeneities, with del(3p) being regarded as the common earliest event followed by three early departure points: VHL and PBRM1 mutations, del(14q) and other somatic copy number alterations (SCNAs) including amp(7), del(1p) and del(6q). We identify three prognostic subtypes of ccRCC with distinct clonal architectures and immune infiltrates: long-lived patients, enriched with VHL but depleted of BAP1 mutations, have high levels of Th17 and CD8+ T cells while short-lived patients with high burden of SCNAs have high levels of Tregs and Th2 cells, highlighting the importance of evaluating evolution patterns in the clinical management of ccRCC.


Assuntos
Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA/genética , Evolução Molecular , Neoplasias Renais/genética , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Células Clonais/imunologia , Células Clonais/metabolismo , Estudos de Coortes , Regulação Neoplásica da Expressão Gênica , Heterogeneidade Genética , Humanos , Rim/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Mutação , Proteínas Nucleares/genética , Prognóstico , Análise de Sobrevida , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Células Th2/imunologia , Fatores de Transcrição/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Sequenciamento Completo do Genoma
15.
Sci Data ; 6: 190022, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30778257

RESUMO

Elysia chlorotica, a sacoglossan sea slug found off the East Coast of the United States, is well-known for its ability to sequester chloroplasts from its algal prey and survive by photosynthesis for up to 12 months in the absence of food supply. Here we present a draft genome assembly of E. chlorotica that was generated using a hybrid assembly strategy with Illumina short reads and PacBio long reads. The genome assembly comprised 9,989 scaffolds, with a total length of 557 Mb and a scaffold N50 of 442 kb. BUSCO assessment indicated that 93.3% of the expected metazoan genes were completely present in the genome assembly. Annotation of the E. chlorotica genome assembly identified 176 Mb (32.6%) of repetitive sequences and a total of 24,980 protein-coding genes. We anticipate that the annotated draft genome assembly of the E. chlorotica sea slug will promote the investigation of sacoglossan genetics, evolution, and particularly, the genetic signatures accounting for the long-term functioning of algal chloroplasts in an animal.


Assuntos
Gastrópodes/genética , Genoma , Animais , Anotação de Sequência Molecular , Fotossíntese
16.
Int J Mol Sci ; 20(2)2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30646613

RESUMO

Dipeptidyl peptidase IV (DPP-IV) inhibitors occupy a growing place in the drugs used for the management of type 2 diabetes. Recently, food components, including food-derived bioactive peptides, have been suggested as sources of DPP-IV inhibitors without side effects. Chinese black tea is a traditional health beverage, and it was used for finding DPP-IV inhibitory peptides in this study. The ultra-filtrated fractions isolated from the aqueous extracts of black tea revealed DPP-IV inhibitory activity in vitro. Four peptides under 1 kDa were identified by SDS-PAGE and LC-MS/MS (Liquid Chromatography-Mass Spectrometry-Mass Spectrometry) from the ultra-filtrate. The peptide II (sequence: AGFAGDDAPR), with a molecular mass of 976 Da, showed the greatest DPP-IV inhibitory activity (in vitro) among the four peptides. After administration of peptide II (400 mg/day) for 57 days to streptozotocin (STZ)-induced hyperglycemic mice, the concentration of glucagon-like peptide-1 (GLP-1) in the blood increased from 9.85 ± 1.96 pmol/L to 19.22 ± 6.79 pmol/L, and the insulin level was increased 4.3-fold compared to that in STZ control mice. Immunohistochemistry revealed the improved function of pancreatic beta-cells and suppressed proliferation of pancreatic alpha-cells. This study provides new insight into the use of black tea as a potential resource of food-derived DPP-IV inhibitory peptides for the management of type 2 diabetes.


Assuntos
Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Dipeptidil Peptidase 4/genética , Inibidores da Dipeptidil Peptidase IV/química , Peptídeo 1 Semelhante ao Glucagon/sangue , Células Secretoras de Glucagon/efeitos dos fármacos , Humanos , Células Secretoras de Insulina/efeitos dos fármacos , Camundongos , Chá/química
17.
Nat Commun ; 9(1): 5433, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575759

RESUMO

Tibetan barley (Hordeum vulgare L., qingke) is the principal cereal cultivated on the Tibetan Plateau for at least 3,500 years, but its origin and domestication remain unclear. Here, based on deep-coverage whole-genome and published exome-capture resequencing data for a total of 437 accessions, we show that contemporary qingke is derived from eastern domesticated barley and it is introduced to southern Tibet most likely via north Pakistan, India, and Nepal between 4,500 and 3,500 years ago. The low genetic diversity of qingke suggests Tibet can be excluded as a center of origin or domestication for barley. The rapid decrease in genetic diversity from eastern domesticated barley to qingke can be explained by a founder effect from 4,500 to 2,000 years ago. The haplotypes of the five key domestication genes of barley support a feral or hybridization origin for Tibetan weedy barley and reject the hypothesis of native Tibetan wild barley.


Assuntos
Domesticação , Efeito Fundador , Genoma de Planta , Hordeum/genética , Filogeografia , Tibet
18.
Proc Natl Acad Sci U S A ; 115(45): 11567-11572, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30348779

RESUMO

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.


Assuntos
Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Mutação , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Receptores de Superfície Celular/genética , Adulto , Idade de Início , Animais , Apoptose/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/antagonistas & inibidores , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sequência de Bases , Encéfalo/patologia , Estudos de Casos e Controles , Estudos de Coortes , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/patologia , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Diagnóstico Precoce , Feminino , Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Pais , Doença de Parkinson/diagnóstico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores de Superfície Celular/metabolismo , Irmãos
19.
ACS Appl Mater Interfaces ; 10(40): 34727-34734, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30207676

RESUMO

p-type ternary oxides can be extensively explored as alternative sensing channels to binary oxides with diverse structural and compositional versatilities. Seeking a novel approach to magnify their sensitivities toward gas molecules, e.g., volatile organic compounds (VOCs), will definitely expand their applications in the frontier area of healthcare and air-quality monitoring. In this work, delafossite CuCrO2 (CCO) nanoparticles with different grain sizes have been utilized as p-type ternary oxide sensors. It was found that singly ionized oxygen vacancies (Vo•) defects, compared with the grain size of CCO nanoparticles, play an important role in enhancing the charge exchange at the VOCs molecules/CCO interface. In addition to suppressing the hole concentration of the sensor channel, the unpaired electron trapped in Vo• provides an active site for chemisorptions of environmental oxygen and VOCs molecules. The synergetic effect is responsible for the observed increase of sensitivity. Furthermore, the sensitive (Vo• defect-rich) CCO sensor exhibits good reproducibility and stability under a moderate operation temperature (<325 °C). Our work highlights that Vo• defects, created via either in situ synthesis or postannealing treatment, could be explored to rationally boost the performance of p-type ternary oxide sensors.

20.
Gigascience ; 7(8)2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30101283

RESUMO

With the rapid development of next-generation sequencing technology, ever-increasing quantities of genomic data pose a tremendous challenge to data processing. Therefore, there is an urgent need for highly scalable and powerful computational systems. Among the state-of-the-art parallel computing platforms, Apache Spark is a fast, general-purpose, in-memory, iterative computing framework for large-scale data processing that ensures high fault tolerance and high scalability by introducing the resilient distributed dataset abstraction. In terms of performance, Spark can be up to 100 times faster in terms of memory access and 10 times faster in terms of disk access than Hadoop. Moreover, it provides advanced application programming interfaces in Java, Scala, Python, and R. It also supports some advanced components, including Spark SQL for structured data processing, MLlib for machine learning, GraphX for computing graphs, and Spark Streaming for stream computing. We surveyed Spark-based applications used in next-generation sequencing and other biological domains, such as epigenetics, phylogeny, and drug discovery. The results of this survey are used to provide a comprehensive guideline allowing bioinformatics researchers to apply Spark in their own fields.


Assuntos
Genômica/instrumentação , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Animais , Biologia Computacional/instrumentação , Biologia Computacional/métodos , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Camundongos , Software
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA