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1.
Sci Total Environ ; : 143040, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33129518

RESUMO

Plastics have been recognized as a serious threat to the environment. Besides their own toxicity, microplastics can interact with other environmental pollutants, acting as carriers and potentially modulating their toxicity. In this study, the toxicity of polystyrene (PS) microplastic fragments (plain PS; carboxylated PS, PS-COOH and aminated PS, PS-NH2) and triphenyl phosphate (TPhP) (an emerging organophosphate flame retardant) at the environmentally relevant concentrations to the marine medaka (Oryzias melastigma) larvae was investigated. Larvae were exposed to 20 µg/L of microplastic fragments or 20 and 100 µg/L of TPhP or a combination of both for 7 days. The results showed that the three microplastics did not affect the larval locomotor activity. For TPhP, the larval moving duration and distance moved were significantly decreased by the TPhP exposure, with a maximum decrease of 43.5% and 59.4% respectively. Exposure to 100 µg/L TPhP respectively down-regulated the expression levels of sine oculis homeobox homologue 3 (six3) and short wavelength-sensitive type 2 (sws2) by 19.1% and 41.7%, suggesting that TPhP might disturb eye development and photoreception and consequently the low locomotor activity in the larvae. Interestingly, during the binary mixture exposure, the presence of PS, PS-COOH or PS-NH2 reversed the low locomotor activity induced by 100 µg/L TPhP to the normal level. Relative to the larvae from the 100 µg/L TPhP group, the movement duration and distance moved were increased by approximately 60% and 100%, respectively, in the larvae from the TPhP + PS, TPhP + PS-COOH and TPhP + PS-NH2 groups. However, the gene expression profiles were distinct among the fish from the TPhP + PS, TPhP + PS-COOH and TPhP + PS-NH2 groups, implying different mechanisms underlying the reversal of the locomotor activity. The findings in this study challenge the general view that microplastics aggravate the toxicity of the adsorbed pollutants, and help better understand the environmental risk of microplastic pollution.

2.
ISME J ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943748

RESUMO

Cyanobacteria are photosynthetic prokaryotes that inhabit diverse aquatic and terrestrial environments. However, the evolutionary mechanisms involved in the cyanobacterial habitat adaptation remain poorly understood. Here, based on phylogenetic and comparative genomic analyses of 650 cyanobacterial genomes, we investigated the genetic basis of cyanobacterial habitat adaptation (marine, freshwater, and terrestrial). We show: (1) the expansion of gene families is a common strategy whereby terrestrial cyanobacteria cope with fluctuating environments, whereas the genomes of many marine strains have undergone contraction to adapt to nutrient-poor conditions. (2) Hundreds of genes are strongly associated with specific habitats. Genes that are differentially abundant in genomes of marine, freshwater, and terrestrial cyanobacteria were found to be involved in light sensing and absorption, chemotaxis, nutrient transporters, responses to osmotic stress, etc., indicating the importance of these genes in the survival and adaptation of organisms in specific habitats. (3) A substantial fraction of genes that facilitate the adaptation of Cyanobacteria to specific habitats are contributed by horizontal gene transfer, and such genetic exchanges are more frequent in terrestrial cyanobacteria. Collectively, our results further our understandings of the adaptations of Cyanobacteria to different environments, highlighting the importance of ecological constraints imposed by the environment in shaping the evolution of Cyanobacteria.

3.
Gene ; 759: 144964, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32717308

RESUMO

BACKGROUND: Mucosal melanoma is a tumor caused by the malignant transformation of pigment-producing cells and can arise from any mucosal tissue where melanocytes are present. Due to its rarity, the mucosal melanoma subtype is poorly described, and its genetic characteristics are infrequently studied. The discovery or confirmation of new mucosal melanoma susceptibility genes will provide important insights for the study of its pathogenesis. MATERIALS AND METHODS: We performed deep targeted sequencing of 100 previously reported melanoma-related genes in 39 mucosal melanoma samples and a gene-level loss-of-function (LOF) variant enrichment analysis for mucosal melanoma from different incidence sites. RESULTS: We detected 7,589 variants in these samples, and 484 were LOF variants (gain or loss of a stop codon, missense, and splice site). Four different gene-level enrichment analyses revealed that FSIP1 (fibrous sheath interacting protein 1) is a susceptibility gene for oral mucosal melanoma (OR = 0.33, PChi = 4.05 × 10-2, Pburden = 3.06 × 10-2, Pskat = 3.01 × 10-2, Pskato = 3.01 × 10-2), whereas the different methods did not detect a significant susceptibility gene for the other subtypes. CONCLUSIONS: In our study, a susceptibility gene for oral mucosal melanoma was confirmed in a Chinese Han population, and these findings contribute to a better genetic understanding of mucosal melanoma of different subtypes.


Assuntos
Proteínas de Transporte/genética , Mutação com Perda de Função , Melanoma/genética , Proteínas de Plasma Seminal/genética , Idoso , Feminino , Humanos , Masculino , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/classificação , Melanoma/patologia , Pessoa de Meia-Idade , Membrana Mucosa/metabolismo , Membrana Mucosa/patologia
4.
Mar Pollut Bull ; 158: 111349, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32573451

RESUMO

Microplastic (MP) pollution is an emerging contaminant in aquatic environments worldwide. Nonetheless, the developmental toxicity of MPs in the early life stages of fish and the mechanisms involved are not yet fully understood. The present study investigated the effects of different concentrations of polystyrene (PS) MPs on the early development of the marine model fish the medaka Oryzias melastigma. Our results showed that waterborne exposure to PS MPs significantly delayed the hatching time, altered the heartbeat and decreased the hatching rate of embryos. Furthermore, the genes involved in cardiac development, encoding for embryo-hatching enzymes, as well as inflammatory responses were significantly upregulated. The transcriptome results showed that mainly the pathways involved in metabolism, immune response, genetic information processing and diseases were significantly enriched. These results demonstrate that PS MPs negatively impact embryogenesis and the immune response of O. melastigma.


Assuntos
Oryzias , Poluentes Químicos da Água , Animais , Desenvolvimento Embrionário , Microplásticos , Plásticos
5.
Mar Pollut Bull ; 154: 111089, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32319918

RESUMO

Investigating the heterogeneous distribution pattern of plastic pollution in river systems is useful for better understanding the transport pathways of plastics from land to sea. Therefore, we analyzed samples from 17 sites to evaluate the distribution pattern of microplastics (MPs) in Minjiang River Watershed. The MP concentrations ranged between 0.12 and 2.72 n/L, with higher microplastic concentrations located in urban areas with greater population and gross domestic product (GDP) densities. MP concentrations were positively correlated with population density, GDP density, and built-up land use percentage, suggesting that increasing urbanization level will lead to greater plastic pollution. MP concentrations spanning the upstream and downstream sides of the SK Hydropower Dam showed decreasing trends, suggesting that MP settling would occur behind the dam and Shuikou Reservoir might serve as a sink for MPs. This study provides useful insight for revealing the effects of urbanization and dams on spatial distribution of riverine MPs.


Assuntos
Plásticos , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , Microplásticos , Urbanização
6.
J Invest Dermatol ; 140(4): 799-805.e1, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31376382

RESUMO

Most psoriasis-related genes or loci identified by GWAS represent common clusters and are located in noncoding regions of the human genome, providing only limited evidence for the roles of rare coding variants in psoriasis. Two exome-wide case-control genotyping data sets (11,245 cases and 11,177 controls) were obtained from our previous study. Quality controls were established for each data set, and the markers remaining in each set were annotated using ANNOVAR. Gene-based analysis was performed on the annotation results. A total of 250 and 35 genes in the Exome_Fine and Exome_Asian array cohorts, respectively, exceeded the threshold (P < 4.43 × 10-6). Merged gene-based analysis was then conducted on the same set of SNPs from seven genes common to both arrays, and the chi-square test was used to confirm all gene-based results. Ultimately, four susceptibility genes were identified: BBS7 (Pcombine = 1.38 × 10-29), GSTCD (Pcombine = 8.35 × 10-47), LIPK (Pcombine = 1.02 × 10-19), and PPP4R3B (Pcombine = 1.79 × 10-33). This study identified four susceptibility genes for psoriasis via a gene-based method using rare variants, contributing to our understanding of the pathogenesis of psoriasis.

7.
Fish Shellfish Immunol ; 93: 1007-1017, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31449978

RESUMO

Pathogenic disease is a major factor affecting the aquaculture of the rockfish Sebastiscus marmoratus, an important commercial species inhabiting the nearshore waters of the Western Pacific Ocean. Antimicrobial peptides (AMPs), as critical components of innate immunity, have been considered as promising antibiotic substitutes. The aims of this study were 1) to identify major AMPs in the rockfish, 2) to assess their antimicrobial activity and 3) to evaluate their potential therapeutic application. Six AMPs were identified, Hepcidin 1, liver-expressed antimicrobial peptide 2 (LEAP-2), Piscidin, Moronecidin, NK-lysin and ß-defensin through analysis of the liver transcriptome of S. marmoratus. The transcriptional expression profiles of these AMPs were investigated by real-time quantitative PCR (RT-qPCR). These AMPs showed tissue-specific distribution patterns, and S. marmoratus displays a time-, dose- and tissue-dependent expression of AMPs in response to lipopolysaccharide (LPS) challenge. While the synthetic peptides of LEAP-2 and Moronecidin exerted broad-spectrum antimicrobial activity against important aquatic pathogens in vitro by directly disrupting microbial membrane, and no cytotoxicity against murine hepatic cells was observed at the effective concentrations from 5 µM to 40 µM. The existence of multiple AMPs and their distinct tissue distribution patterns and inducible expression patterns suggests a sophisticated, highly redundant, and multilevel network of antimicrobial defensive mechanisms of S. marmoratus. Therefore, S. marmoratus-derived AMPs appear to be potential therapeutic applications against pathogen infections in aquaculture.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/imunologia , Perciformes/genética , Perciformes/imunologia , Animais , Anti-Infecciosos/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Linhagem Celular , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Humanos , Lipopolissacarídeos/farmacologia , Camundongos , Perciformes/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-30315922

RESUMO

Nonylphenol (NP) and Cadmium (Cd) are two common contaminants that can be detected in aquatic environments. Nevertheless, the combined toxicity of NP and Cd at environmentally relevant concentrations in aquatic organisms has not been thoroughly characterized to date. In the present study, the interactions between NP and Cd on male Sebastiscus marmoratus were studied. After 21 days of exposure, the brain aromatase activity was observed to be significantly induced by 100 ng/L NP and 40 µg/L Cd, whereas all of the concentrations of co-treatment resulted in an increase in brain aromatase activity. Additionally, NP could also reduce plasma testosterone concentration, while NP, Cd and their mixture could induce plasma 17ß-estradiol (E2) concentration and VTG concentration. The interactions between NP and Cd on the reproductive physiology were antagonism. Our results also support the notion of using these indicators as biomarkers for exposure to EDCs and further extend the boundary of biomonitoring to environmental levels.


Assuntos
Cádmio/toxicidade , Genitália Masculina/efeitos dos fármacos , Infertilidade Masculina/veterinária , Perciformes/fisiologia , Fenóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Aromatase/química , Aromatase/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Sinergismo Farmacológico , Disruptores Endócrinos/toxicidade , Biomarcadores Ambientais/efeitos dos fármacos , Estradiol/agonistas , Estradiol/sangue , Doenças dos Peixes/sangue , Doenças dos Peixes/induzido quimicamente , Doenças dos Peixes/metabolismo , Doenças dos Peixes/fisiopatologia , Proteínas de Peixes/agonistas , Proteínas de Peixes/metabolismo , Genitália Masculina/fisiopatologia , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Concentração Osmolar , Perciformes/sangue , Testosterona/antagonistas & inibidores , Testosterona/sangue , Testes de Toxicidade Crônica , Vitelogeninas/sangue , Vitelogeninas/química
9.
J Virol ; 92(24)2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30258009

RESUMO

Adult T-cell leukemia (ATL) is a highly aggressive T-cell malignancy induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Long noncoding RNA (lncRNA) plays a critical role in the development and progression of multiple human cancers. However, the function of lncRNA in HTLV-1-induced oncogenesis has not been elucidated. In the present study, we show that the expression level of the lncRNA ANRIL was elevated in HTLV-1-infected cell lines and clinical ATL samples. E2F1 induced ANRIL transcription by enhancing its promoter activity. Knockdown of ANRIL in ATL cells repressed cellular proliferation and increased apoptosis in vitro and in vivo As a mechanism for these actions, we found that ANRIL targeted EZH2 and activated the NF-κB pathway in ATL cells. This activation was independent of the histone methyltransferase (HMT) activity of EZH2 but required the formation of an ANRIL/EZH2/p65 ternary complex. A chromatin immunoprecipitation assay revealed that ANRIL/EZH2 enhanced p65 DNA binding capability. In addition, we observed that the ANRIL/EZH2 complex repressed p21/CDKN1A transcription through H3K27 trimethylation of the p21/CDKN1A promoter. Taken together, our results implicate that the lncRNA ANRIL, by cooperating with EZH2, supports the proliferation of HTLV-1-infected cells, which is thought to be critical for oncogenesis.IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia (ATL), which is a unique malignancy of CD4+ T cells. A role for long noncoding RNA (lncRNA) in HTLV-1-mediated cellular transformation has not been described. In this study, we demonstrated that the lncRNA ANRIL was important for maintaining the proliferation of ATL cells in vitro and in vivo ANRIL was shown to activate NF-κB signaling through forming a ternary complex with EZH2 and p65. Furthermore, epigenetic inactivation of p21/CDKN1A was involved in the oncogenic function of ANRIL. To the best of our knowledge, this is the first study to address the regulatory role of the lncRNA ANRIL in ATL and provides an important clue to prevent or treat HTLV-1-associated human diseases.


Assuntos
Fator de Transcrição E2F1/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Leucemia-Linfoma de Células T do Adulto/patologia , RNA Longo não Codificante/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células Jurkat , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Transplante de Neoplasias , Transdução de Sinais , Regulação para Cima
10.
Sheng Wu Gong Cheng Xue Bao ; 34(9): 1491-1499, 2018 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-30255683

RESUMO

We studied the effect of celastrol on the proliferation and apoptosis of adult T-cell leukemia (ATL) cells. After treating adult T-cell leukemia cell lines with different concentrations of celastrol, we analyzed the cell proliferation by MTT and colony formation assays. Flow cytometry was conducted to detect cell apoptosis by Annexin V-FITC/PI staining. Western blotting and dual-luciferase reporter assay were done to study the mechanism how celastrol suppressed the growth of adult T-cell leukemia cells. Celastrol could significantly inhibit the proliferation of adult T-cell leukemia cells, and induce apoptosis of ATL cells. With the increase of the concentration of celastrol, the ratio of Bax/Bcl-2 protein was up-regulated. The Caspase-3/7 protein was cleaved and activated after treatment with celastrol. Moreover, the expression of HTLV-1-encoded viral protein Tax was significantly inhibited in the celastrol treated cells. Taken together, these results indicated that celastrol effectively inhibited the proliferation of adult T-cell leukemia cells by regulating the expression of Bcl-2 family protein, and induced cell apoptosis by activating Caspase dependent pathway. In addition, celastrol could inhibit the expression of viral protein Tax. This study will provide an experimental basis for the clinical application of celastrol in the treatment of adult T-cell leukemia.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Leucemia-Linfoma de Células T do Adulto/patologia , Triterpenos/farmacologia , Linhagem Celular Tumoral , Produtos do Gene tax/metabolismo , Humanos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico
11.
Chemosphere ; 209: 298-306, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29933166

RESUMO

The seafloor is recognized as one of the major sinks for microplastics (MPs). However, to date there have been no studies reported the MP contamination in benthic organisms from the Arctic and sub-Arctic regions. Therefore, this study provided the first data on the abundances and characteristics of MPs in a total of 413 dominant benthic organisms representing 11 different species inhabiting in the shelf of Bering and Chukchi Seas. The mean abundances of MP uptake by the benthos from all sites ranged from 0.02 to 0.46 items g-1 wet weight (ww) or 0.04-1.67 items individual-1, which were lower values than those found in other regions worldwide. The highest value appeared at the northernmost site, implying that the sea ice and the cold current represent possible transport mediums. Interestingly, the predator A. rubens ingested the maximum quantities of MPs, suggesting that the trophic transfer of MPs through benthic food webs may play a critical role. Fibers constituted the major type (87%) in each species, followed by film (13%). The colors of fibers were classified as red (46%) and transparent (41%), and the film was all gray. The predominant composition was polyamide (PA) (46%), followed by polyethylene (PE) (23%), polyester (PET) (18%) and cellophane (CP) (13%). The most common sizes of MPs concentrated in the interval from 0.10 to 1.50 mm, and the mean size was 1.45 ±â€¯0.13 mm. Further studies about the temporal trends and detrimental effects of MPs remain to be carried out in benthic organisms from the Arctic and sub-Arctic regions.


Assuntos
Plásticos/efeitos adversos , Animais , Regiões Árticas , Plásticos/química
12.
Genome Biol Evol ; 9(8): 1998-2012, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28830116

RESUMO

The interordinal relationships of Laurasiatherian mammals are currently one of the most controversial questions in mammalian phylogenetics. Previous studies mainly relied on coding sequences (CDS) and seldom used noncoding sequences. Here, by data mining public genome data, we compiled an intron data set of 3,638 genes (all introns from a protein-coding gene are considered as a gene) (19,055,073 bp) and a CDS data set of 10,259 genes (20,994,285 bp), covering all major lineages of Laurasiatheria (except Pholidota). We found that the intron data contained stronger and more congruent phylogenetic signals than the CDS data. In agreement with this observation, concatenation and species-tree analyses of the intron data set yielded well-resolved and identical phylogenies, whereas the CDS data set produced weakly supported and incongruent results. Further analyses showed that the phylogeny inferred from the intron data is highly robust to data subsampling and change in outgroup, but the CDS data produced unstable results under the same conditions. Interestingly, gene tree statistical results showed that the most frequently observed gene tree topologies for the CDS and intron data are identical, suggesting that the major phylogenetic signal within the CDS data is actually congruent with that within the intron data. Our final result of Laurasiatheria phylogeny is (Eulipotyphla,((Chiroptera, Perissodactyla),(Carnivora, Cetartiodactyla))), favoring a close relationship between Chiroptera and Perissodactyla. Our study 1) provides a well-supported phylogenetic framework for Laurasiatheria, representing a step towards ending the long-standing "hard" polytomy and 2) argues that intron within genome data is a promising data resource for resolving rapid radiation events across the tree of life.


Assuntos
Eutérios/genética , Filogenia , Animais , Quirópteros/genética , Bases de Dados Genéticas , Evolução Molecular , Íntrons
13.
Oncologist ; 22(8): 890-894, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28408616

RESUMO

BACKGROUND: Breast cancer is a heterogeneous and polygenic disease that can be divided into different molecular subtypes based on histological and genomic features. To date, numerous susceptibility loci of breast cancer have been discovered by genome-wide association studies and may expand the genetic features. However, few loci have been further studied according to molecular subtypes. MATERIALS AND METHODS: We genotyped 23 recently discovered single nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes) and 3,036 healthy controls. RESULTS: Through a stratification analysis, 5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and 7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2 (rs35054928) was associated with Luminal B. CONCLUSION: In our study, breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes. IMPLICATIONS FOR PRACTICE: To date, genome-wide association studies have identified more than 90 susceptibility loci associated with breast cancer. However, few loci have been further studied according to molecular subtype. The results of this study are that breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes.


Assuntos
Neoplasias da Mama/genética , MAP Quinase Quinase Quinase 1/genética , RNA Longo não Codificante/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Adulto , Idoso , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , China , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
14.
Angew Chem Int Ed Engl ; 56(3): 722-727, 2017 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-27936319

RESUMO

White-light-emitting materials with high mobility are necessary for organic white-light-emitting transistors, which can be used for self-driven OLED displays or OLED lighting. In this study, we combined two materials with similar structures-2-fluorenyl-2-anthracene (FlAnt) with blue emission and 2-anthryl-2-anthracence (2A) with greenish-yellow emission-to fabricate OLED devices, which showed unusual solid-state white-light emission with the CIE coordinates (0.33, 0.34) at 10 V. The similar crystal structures ensured that the OTFTs based on mixed FlAnt and 2A showed high mobility of 1.56 cm2 V-1 s-1 . This simple method provides new insight into the design of high-performance white-emitting transistor materials and structures.

15.
Am J Transl Res ; 8(11): 4844-4856, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904685

RESUMO

Ixodes scapularis, the black-legged tick, is one of the most common human-disease vectors and transmits Borrelia species, such as B. burgdorferi, as well as Theileria microti, Anaplasma phagocytophilum, etc. As basic helix-loop-helix (bHLH) transcription factors have been recognized for many years as important regulators of various developmental processes, we performed phylogenetic analysis of the black-legged tick genome in order to identify the number and family of bHLH transcription factors. Because bHLH family members have been identified in many organisms, including silkworm and fruit fly, we were able to conduct this survey and identify 58 putative bHLH transcription factors. Phylogenetic analysis revealed that the black-legged tick has 26, 10, 9, 1, 9, and 1 member in groups A, B, C, D, E, and F, respectively, whereas two were orphan genes. This analysis also revealed that unlike silkworm and fruit fly, the black-legged tick has no Mesp, Mlx, or TF4 family members, but has one more MyoRb family member. The present study provides useful background information for future studies of the black-legged tick as a disease vector with the goal of prevention and treatment.

16.
Breast Cancer Res Treat ; 159(3): 433-42, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27572337

RESUMO

To date, many loci associated with breast cancer have been identified through genome-wide association studies; most of these studies were conducted using populations of European descent. Thus, it is not clear whether these susceptibility loci are also risk factors for Chinese populations. We selected and genotyped 32 single nucleotide polymorphisms (SNPs) using the Sequenom iPLEX platform in a female Chinese cohort of 3036 breast cancer cases and 3036 healthy controls. A total of 23 SNPs passed the quality control test. The associations of these SNPs with disease susceptibility were assessed using logistic regression, adjusting for age. The Bonferroni correction was used to conservatively account for multiple testing, and the threshold for statistical significance was P < 2.17 × 10(-3) (0.05/23). We confirmed ten risk-associated variants within three reported breast cancer susceptibility loci in a Chinese Han population: 5q11.2 (rs16886181, P = 5.29 × 10(-6), OR = 1.19; rs1017226, P = 5.24 × 10(-4), OR = 1.22; rs16886034, P = 2.00 × 10(-3), OR = 1.21; rs16886113, P = 1.24 × 10(-3), OR = 1.20; rs16886364, P = 9.20 × 10(-4), OR = 1.21; rs16886397, P = 1.17 × 10(-3), OR = 1.20; rs16886448, P = 1.62 × 10(-3,)OR = 1.20; and rs2229882, P = 5.14 × 10(-4), OR = 1.31), 5q14.3 (rs421379, P = 2.83 × 10(-13), OR = 1.83), and 10q26.1 (rs35054928, P = 7.73 × 10(-6), OR = 1.18). The 10q26.1 locus was found to be a susceptibility locus for breast cancer in Chinese Han women in our previous studies. 5q11.2 and 5q14.3 are confirmed here for the first time as susceptibility loci for breast cancer in Chinese Han women. This study reports three breast cancer susceptibility loci that were previously identified in European populations and are also risk factors for Chinese populations. This study may extend the genetic basis of breast cancer in Chinese Han women and highlight the contribution of multiple variants of modest effect.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , China/etnologia , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 5/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Pessoa de Meia-Idade
17.
Bing Du Xue Bao ; 32(2): 235-42, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27396170

RESUMO

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus demonstrated to be associated with human disease. Infection by the HTLV-1 can cause T-cell leukemia (ATL) in adults. HTLV-1 bZIP factor (HBZ) is a viral protein encoded by the minus strand of the HTLV-1 provirus. Among the regulatory and accessory genes of HTLV-1, HBZ is the only gene that remains intact and which is expressed consistently in all patients with ATL. Moreover, HBZ has a critical role in the leukemogenesis of ATL. Here, we review the function of HBZ in the oncogenesis of HTLV-1 and its molecular mechanism of action.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/metabolismo , Leucemia de Células T/virologia , Proteínas dos Retroviridae/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Carcinogênese , Infecções por HTLV-I/patologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia de Células T/patologia , Proteínas dos Retroviridae/genética
18.
Nat Genet ; 48(7): 740-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27213287

RESUMO

The human major histocompatibility complex (MHC) region has been shown to be associated with numerous diseases. However, it remains a challenge to pinpoint the causal variants for these associations because of the extreme complexity of the region. We thus sequenced the entire 5-Mb MHC region in 20,635 individuals of Han Chinese ancestry (10,689 controls and 9,946 patients with psoriasis) and constructed a Han-MHC database that includes both variants and HLA gene typing results of high accuracy. We further identified multiple independent new susceptibility loci in HLA-C, HLA-B, HLA-DPB1 and BTNL2 and an intergenic variant, rs118179173, associated with psoriasis and confirmed the well-established risk allele HLA-C*06:02. We anticipate that our Han-MHC reference panel built by deep sequencing of a large number of samples will serve as a useful tool for investigating the role of the MHC region in a variety of diseases and thus advance understanding of the pathogenesis of these disorders.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único/genética , Psoríase/genética , Butirofilinas/genética , Estudos de Casos e Controles , China/epidemiologia , Predisposição Genética para Doença , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DP/genética , Humanos , Psoríase/epidemiologia
19.
J Invest Dermatol ; 136(4): 779-787, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26743604

RESUMO

Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.


Assuntos
Metilação de DNA , Epigenômica , Estudo de Associação Genômica Ampla , Psoríase/genética , Pele/metabolismo , Proteínas Argonauta/genética , Ácido Aspártico Endopeptidases/genética , Ilhas de CpG , Sistema Enzimático do Citocromo P-450/genética , Enzimas Conversoras de Endotelina , Epigênese Genética , Variação Genética , Humanos , Leucócitos Mononucleares/metabolismo , Manosidases/genética , Metaloendopeptidases/genética , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Proteínas Associadas SAP90-PSD95 , Pele/patologia
20.
Mol Ecol Resour ; 16(1): 91-102, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-25959587

RESUMO

In phylogenetics and population genetics, a large number of loci are often needed to accurately resolve species relationships. Normally, loci are enriched by PCR and sequenced by Sanger sequencing, which is expensive when the number of amplicons is large. Next-generation sequencing (NGS) techniques are increasingly used for parallel amplicon sequencing, which reduces sequencing costs tremendously, but has not reduced preparation costs very much. Moreover, for most current NGS methods, amplicons need to be purified and quantified before sequencing and their lengths are also restricted (normally <700 bp). Here, we describe an approach to sequence pooled amplicons of any length using the Illumina platform. Using this method, amplicons are pooled at equal volume rather than at equal concentration, thus eliminating the laborious purification and quantification steps. We then shear the pooled amplicons, repair the ends, add sample identifying linkers and pool multiple samples prior to Illumina library preparation. Data are then assembled using the transcriptome assembly program trinity, which is optimized to deal with templates of highly varying quantities. We demonstrated the utility of our approach by recovering 93.5% of the target amplicons (size up to 1650 bp) in full length for a 16 taxa × 101 loci project, using ~2.0 GB of Illumina HiSeq paired-end 90-bp data. Overall, we validate a rapid, cost-effective and scalable approach to sequence a large number of targeted loci from a large number of samples that is particularly suitable for both phylogenetics and population genetics studies that require a modest scale of data.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mamíferos/genética , Transcriptoma , Animais , Mamíferos/classificação , Filogenia , Reação em Cadeia da Polimerase
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