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1.
Cell Commun Signal ; 18(1): 16, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005247

RESUMO

BACKGROUND: The role and mechanism of the nicotinamide adenine dinucleotide (NAD+) salvage pathway in cancer cell proliferation is poorly understood. Nicotinamide phosphoribosyltransferase (NAMPT), which converts nicotinamide into NAD+, is the rate-limiting enzyme in the NAD+ salvage pathway. Here, we assessed the role of NAMPT in the proliferation of colorectal cancer. METHODS: Real-time PCR, immunohistochemistry, western blotting, and analyses of datasets from Oncomine and Gene Expression Omnibus were conducted to assess the expression of NAMPT at the mRNA and protein levels in colorectal cancer. The Kaplan Meier plotter online tool was used to evaluate the prognostic role of NAMPT. Knockdown of NAMPT was performed to assess the role of NAMPT in colorectal cancer cell proliferation and tumorigenesis both in vitro and in vivo. Overexpression of NAMPT was used to evaluate impact of NAMPT on colorectal cancer cell proliferation in vitro. NAD+ quantitation, immunofluorescence, dual luciferase assay and western blot were used to explore the mechanism of colorectal cancer proliferation. Transwell migration and invasion assays were conducted to assess the role of NAMPT in cell migration and invasion abilities of colorectal cancer cells. RESULTS: Our study indicated that the inhibition of NAMPT decreased proliferation capacity of colorectal cancer cells both in vitro and in vivo. Conversely, overexpression of NAMPT could promote cell proliferation in vitro. NAMPT inhibition induced ß-catenin degradation by increasing Axin expression levels; this resulted in the inhibition of Wnt/ß-catenin signaling and cell proliferation in colorectal cancer. The addition of nicotinamide mononucleotide, the enzymatic product of NAMPT, effectively reversed ß-catenin protein degradation and inhibited growth. Similarly, the knockdown of Axin also decreased the cell death induced by the inhibition of NAMPT. In addition, we showed that colorectal cancer tissues harbored significantly higher levels of NAMPT than the levels harbored by paired normal tissues, especially in colorectal cancer stages I and II. And the overexpression of NAMPT was associated with unfavorable survival results. CONCLUSIONS: Our findings reveal that NAMPT plays an important role in colorectal cancer proliferation via Wnt/ß-catenin pathway, which could have vital implications for the diagnosis, prognosis and treatment of colorectal cancer.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31855840

RESUMO

Oxidative RNA damage has been found to be associated with a variety of diseases, and 8-hydroxyguanosine (8-OHG) is a typical marker of oxidative modification of RNA. This guanosine modification is an emerging biomarker for disease detection and determination of 8-OHG in human urine is favored because it is noninvasive to patients. However, due to its poor ionization efficiency in mass spectrometry and trace amount in urine, accurate quantification of this modified nucleoside is still challenging. Herein, a rapid, accurate, sensitive and robust method using solid-phase extraction (SPE) combined with isotope dilution ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed for detection of this oxidative RNA modification in human urine. The limit of detection can reach 1.5 fmol and the method exhibits good precision on intra-day (1.8-3.3%) and inter-day (0.6-1.2%) analyses. Satisfactory recovery (87.5-107.2%) at three spiked levels was achieved by using HLB cartridge for urine pretreatment. Using this method, we quantified 8-OHG in urine from 65 colorectal cancer (CRC) patients and 76 healthy volunteers. The measured level of urinary 8-OHG for CRC patients and healthy controls is 1.91 ± 0.63 nmol/mmol creatinine and 1.33 ± 0.35 nmol/mmol creatinine, respectively. We found the content of 8-OHG in urine was raised in CRC patients patients, implying this oxidative RNA modification marker could act as a potential noninvasive indicator for early screening of CRC. In addition, this study will make contributions to the investigations of the influences of oxidative stress on the formation and development of CRC.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Neoplasias Colorretais/diagnóstico , Guanosina/análogos & derivados , RNA/urina , Espectrometria de Massas em Tandem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Neoplasias Colorretais/urina , Guanosina/química , Guanosina/urina , Humanos , Limite de Detecção , Modelos Lineares , Pessoa de Meia-Idade , Estresse Oxidativo , RNA/química , Reprodutibilidade dos Testes
3.
Am J Hum Genet ; 105(6): 1237-1253, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31785787

RESUMO

We report an early-onset autosomal-recessive neurological disease with cerebellar atrophy and lysosomal dysfunction. We identified bi-allelic loss-of-function (LoF) variants in Oxidative Resistance 1 (OXR1) in five individuals from three families; these individuals presented with a history of severe global developmental delay, current intellectual disability, language delay, cerebellar atrophy, and seizures. While OXR1 is known to play a role in oxidative stress resistance, its molecular functions are not well established. OXR1 contains three conserved domains: LysM, GRAM, and TLDc. The gene encodes at least six transcripts, including some that only consist of the C-terminal TLDc domain. We utilized Drosophila to assess the phenotypes associated with loss of mustard (mtd), the fly homolog of OXR1. Strong LoF mutants exhibit late pupal lethality or pupal eclosion defects. Interestingly, although mtd encodes 26 transcripts, severe LoF and null mutations can be rescued by a single short human OXR1 cDNA that only contains the TLDc domain. Similar rescue is observed with the TLDc domain of NCOA7, another human homolog of mtd. Loss of mtd in neurons leads to massive cell loss, early death, and an accumulation of aberrant lysosomal structures, similar to what we observe in fibroblasts of affected individuals. Our data indicate that mtd and OXR1 are required for proper lysosomal function; this is consistent with observations that NCOA7 is required for lysosomal acidification.

4.
J Cancer ; 10(26): 6618-6634, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777591

RESUMO

Introduction: Abnormal status of gene expression plays an important role in tumorigenesis, progression and metastasis of breast cancer. Mechanisms of gene silence or activation were varied. Methylation of genes may contribute to alteration of gene expression. This study aimed to identify differentially expressed hub genes which may be regulated by DNA methylation and evaluate their prognostic value in breast cancer by bioinformatic analysis. Methods: GEO2R was used to obtain expression microarray data from GSE54002, GSE65194 and methylation microarray data from GSE20713, GSE32393. Differentially expressed-aberrantly methylated genes were identified by FunRich. Biological function and pathway enrichment analysis were conducted by DAVID. PPI network was constructed by STRING and hub genes was sorted by Cytoscape. Expression and DNA methylation of hub genes was validated by UALCAN and MethHC. Clinical outcome analysis of hub genes was performed by Kaplan Meier-plotter database for breast cancer. IHC was performed to analyze protein levels of EXO1 and Kaplan-Meier was used for survival analysis. Results: 677 upregulated-hypomethylated and 361 downregulated-hypermethylated genes were obtained from GSE54002, GSE65194, GSE20713 and GSE32393 by GEO2R and FunRich. The most significant biological process, cellular component, molecular function enriched and pathway for upregulated-hypomethylated genes were viral process, cytoplasm, protein binding and cell cycle respectively. For downregulated-hypermethylated genes, the result was peptidyl-tyrosine phosphorylation, plasma membrane, transmembrane receptor protein tyrosine kinase activity and Rap1 signaling pathway (All p< 0.05). 12 hub genes (TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2) were sorted from 677 upregulated-hypomethylated genes. 4 hub genes (EGFR, FGF2, BCL2, PIK3R1) were sorted from 361 downregulated-hypermethylated genes. Differential expression of 16 hub genes was validated in UALCAN database (p<0.05). 7 in 12 upregulated-hypomethylated and 2 in 4 downregulated-hypermethylated hub genes were confirmed to be significantly hypomethylated or hypermethylated in breast cancer using MethHC database (p<0.05). Finally, 12 upregulated hub genes (TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2) and 3 downregulated genes (FGF2, BCL2, PIK3R1) contributed to significant unfavorable clinical outcome in breast cancer (p<0.05). High expression level of EXO1 protein was significantly associated with poor OS in breast cancer patients (p=0.03). Conclusion: Overexpression of TOP2A, MAD2L1, FEN1, EPRS, EXO1, MCM4, PTTG1, RRM2, PSMD14, CDKN3, H2AFZ, CCNE2 and downregulation of FGF2, BCL2, PIK3R1 might serve as diagnosis and poor prognosis biomarkers in breast cancer by more research validation. EXO1 was identified as an individual unfavorable prognostic factor. Methylation might be one of the major causes leading to abnormal expression of those genes. Functional analysis and pathway enrichment analysis of those genes would provide novel ideas for breast cancer research.

5.
Seizure ; 72: 49-53, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31600677

RESUMO

PURPOSE: Japanese encephalitis (JE), the main cause of viral encephalitis in Asia, usually presents with acute symptomatic seizures; however, there have been very few systematic reports regarding late unprovoked seizures and epilepsy. We aimed to describe the clinical features and outcomes of post-encephalitic epilepsy following JE. METHODS: Patients with epilepsy with a previous confirmed diagnosis of JE visiting West China Hospital from 2013 to 2019 were enrolled in the observational case-controlled study. Patients with epilepsy with a history of other non-specific viral encephalitis were enrolled as controls. For all enrolled subjects, disease related information was recorded. RESULTS: Forty-eight patients with JE (20 males; median age, 21.0 years; average epilepsy duration, 8.55 years) were identified. The median duration from JE to the first unprovoked seizure was 7.73 years, which significantly differed from that of the controls (7.73 vs. 2.69 years, respectively; p = 4.59 × 10-6). Most patients had focal epilepsy, and 29 (78.38%) were drug resistant. Among 45 patients with available neuroimaging data, three in fourth had no obvious abnormality, and the temporal lobe and hippocampus (22.22%) were the most affected brain regions. Six patients had surgery, and three achieved class-one seizure-free status. CONCLUSION: The latency to the first unprovoked seizure was longer in patients with JE than controls. Regarding chronic epilepsy, three in four had structural abnormalities, and the long-term outcomes of post-encephalitic epilepsy following JE were poor. Surgery remains an option for drug-resistant epilepsy.

6.
Ann Clin Transl Neurol ; 6(10): 1980-1988, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509352

RESUMO

OBJECTIVE: To characterize the natural history and clinical features of myopathies caused by mono-allelic, dominantly acting pathogenic variants in COL12A1. METHODS: Patients with dominant COL12A1-related myopathies were characterized by history and clinical examination, muscle imaging, and genetic analysis. Pathogenicity of the variants was assessed by immunostaining patient-derived dermal fibroblast cultures for collagen XII. RESULTS: Four independent families with childhood-onset weakness due to novel, dominantly acting pathogenic variants in COL12A1 were identified. Adult patients exhibited distal-predominant weakness. Three families carried dominantly acting glycine missense variants, and one family had a heterozygous, intragenic, in-frame deletion of exon 52 of COL12A1. All pathogenic variants resulted in increased intracellular retention of collagen XII in patient-derived fibroblasts as well as loss of extracellular, fibrillar collagen XII deposition. Since haploinsufficiency for COL12A1 is largely clinically asymptomatic, we designed and evaluated small interfering RNAs (siRNAs) that specifically target the mutant allele containing the exon 52 deletion. Immunostaining of the patient fibroblasts treated with the siRNA showed a near complete correction of collagen XII staining patterns. INTERPRETATION: This study characterizes a distal myopathy phenotype in adults with dominant COL12A1 pathogenic variants, further defining the phenotypic spectrum and natural history of COL12A1-related myopathies. This work also provides proof of concept of a precision medicine treatment approach by proposing and validating allele-specific knockdown using siRNAs specifically designed to target a patient's dominant COL12A1 disease allele.

7.
Opt Express ; 27(18): 26014-26026, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31510462

RESUMO

At present, researchers are exploring biological tissue detection method using terahertz techniques. In this paper, techniques to inspect mouse liver injury by using terahertz spectroscopy were studied. The boxplots were applied to remove abnormal data, and the maximal information coefficient was employed to select crucial features from the absorption coefficient and refractive index spectra. Random Forests and AdaBoost were applied to recognize different levels of liver injury. We found that AdaBoost had better performance on low-level injury classification. This work suggests that terahertz techniques have the potential to detect liver injury at an early stage and evaluate liver treatment strategies.


Assuntos
Fígado/lesões , Espectroscopia Terahertz/métodos , Algoritmos , Animais , Feminino , Camundongos Endogâmicos BALB C , Camundongos Nus , Refratometria
8.
Seizure ; 71: 179-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382137

RESUMO

PURPOSE: To investigate the current status of marriage and fertility of patients with epilepsy (PWE) and characterize its influencing factors. METHODS: A total of 1,823 adult patients (males age 22 years or older, females age 20 years or older) were included in this study. Data concerning sociodemographic and clinical characteristics were collected. Descriptive analyses, followed by univariate and multivariate logistic regression analyses were utilized to examine factors associated with marriage and fertility of PWE. Marital status of PWE was compared with Chinese population. Standardized marriage rate (SMR) for age and sex was estimated based on the 2010 sixth national population census. RESULTS: 1,132 patients (62.1%) were married and 823 (45.1%) had a history of fertility. Patients had lower marriage rates than Chinese population (62.1% vs 78.4%). Patients with adult-onset epilepsy (>18 years) had a significantly higher rate of marriage and fertility (p < 0.001) compared to those with childhood-onset epilepsy (≤18 years). Employed patients had higher marriage rates than unemployed patients (64.9% vs 58.6%, p = 0.006), with only male patients being significantly affected by employment status (p < 0.001). Multiple logistic regression revealed that age, age at first seizure onset, and employment status were related to both marriage and fertility. CONCLUSION: Epilepsy had negative effects on marriage and fertility status. Marriage and fertility rates were lower in patients with Childhood-onset epilepsy (≤18 years). Furthermore, employment status mainly affected the marriage rate of male patients.

9.
Cell Commun Signal ; 17(1): 79, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331345

RESUMO

BACKGROUND: Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis than patients with microsatellite stable (MSS) CRC. However, some MSI-H CRC patients do not gain overall survival benefits from immune checkpoint-blockade treatment. In other words, heterogeneity within the subgroup of MSI-H tumors remains poorly understood. Thus, an in-depth molecular characterization of MSI-H tumors is urgently required. METHODS: Here, we use nonnegative matrix factorization (NMF)-based consensus clustering to define CRC MSI-H subtypes in The Cancer Genome Atlas and a French multicenter cohort GSE39582. CIBERSORT was used to calculate the proportions of 22 lymphocytes in tumor tissue in MSI-H subtypes. RESULTS: MSI-H CRC samples basically clustered into two subgroups (MSI-H1 and MSI-H2). MSI-H1 was characterized by a lower BRAF mutational status, higher frequency of chromosomal instability, global hypomethylation, and worse survival than MSI-H2. Further examination of the immune landscape showed that macrophages of the M2 phenotype were enriched in MSI-H1, which may be associated with poor prognosis in this subgroup. CONCLUSIONS: Our results illustrate the genetic heterogeneity in MSI-H CRCs and macrophages may serve as good targets for anticancer therapy in MSI-H1.

10.
Epilepsia Open ; 4(2): 302-308, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31168497

RESUMO

Objective: The aim of this study was to evaluate the clinical features and treatment outcomes of patients with juvenile myoclonic epilepsy (JME) in western China. Method: We continuously reviewed one hundred and five outpatients with JME who were diagnosed and treated at the Epilepsy Registration Center of West China Hospital between October 2012 and July 2014. Seizure control stratified into different seizure types and by antiepileptic drugs (AEDs) was prospectively evaluated every 3-6 months. Results: Among 105 patients with JME, eighty-five patients (81%) received monotherapy including valproate (VPA, 47%) and levetiracetam (LEV, 43%) treatment. The rates of seizure freedom 1, 3, and 5 years after the initiation of AED treatment were 64.8% (68/105), 29.5% (31/105), and 14.6% (12/82) in JME patients, respectively. Patients with myoclonic seizure (MS) and absence seizure (AS) were less frequently seizure-free than those with MS and generalized tonic-clonic seizure (GTCS) (P = 0.012). Patients on VPA monotherapy had better control of GTCS than patients on LEV monotherapy (P = 0.036). There is a trend of lower rates of seizure freedom in patients treated with LEV than in those treated with VPA after the first-year treatment period. Significance: Our data suggest that in JME, seizure control is linked to seizure type, possibly allowing a more individualized approach when counseling JME patients.

11.
Cell Death Dis ; 10(5): 352, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040266

RESUMO

Dysregulation of protein tyrosine phosphatase, receptor type B (PTPRB) correlates with the development of a variety of tumors. Here we show that PTPRB promotes metastasis of colorectal cancer (CRC) cells via inducing epithelial-mesenchymal transition (EMT). We find that PTPRB is expressed at significantly higher levels in CRC tissues compared to adjacent nontumor tissues and in CRC cell lines with high invasion. PTPRB knockdown decreased the number of invasive CRC cells in an in vitro wound healing model, and also reduced tumor metastasis in vivo. Conversely, PTPRB overexpression promoted CRC cell invasion in vitro and metastasis in vivo. PTPRB overexpression decreased vimentin expression and promoted E-cadherin expression, consistent with promotion of EMT, while PTPRB knockdown had the opposite effect. Hypoxic conditions induced EMT and promoted invasion in CRC cells, but these effects were eliminated by PTPRB knockdown. EMT blockade via TWIST1 knockdown inhibited the migration and invasiveness of CRC cells, and even increased PTPRB expression could not reverse this effect. Altogether, these data support the conclusion that PTPRB promotes invasion and metastasis of CRC cells via inducing EMT, and that PTPRB would be a novel therapeutic target for the treatment of CRC.

12.
Seizure ; 66: 42-46, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30785055

RESUMO

PURPOSE: This study was conducted to investigate the relevant demographics and clinical factors contributing to seizure-related motor vehicle accidents in west China. METHODS: All driving patients who visited our epilepsy clinic in the West China Hospital, between October 2012 and October 2016, were invited to participate. Data on social demographics, clinical features, and motor vehicle accidents were collected during structured interviews. Binary logistic regression was used to identify factors associated with seizure-related motor vehicle accidents. RESULTS: In total, 519 patients reported driving after being diagnosed with epilepsy. Among them, thirty-nine (7.5%) patients experienced at least one seizure-related motor vehicle accidents. Patients who had seizure-free intervals ≥2 years had a 89% reduced chance of crashing compared to patients with shorter intervals. Logistic regression revealed that the interval of seizure freedom (B = -0.384, P = 0.007), number of antiepileptic drugs (AEDs) taken (B = 0.400, P = 0.041), and type of motor vehicle (B = 0.798, P = 0.021) were independently associated with seizure-related motor vehicle accidents. CONCLUSION: The interval of seizure freedom, number of AEDs taken, and type of motor vehicle should be considered when counseling patients with epilepsy on driving. A longer seizure-free interval suggested a compromised risk of seizure-related motor vehicle accidents.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Epilepsia/epidemiologia , Epilepsia/psicologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Anticonvulsivantes/uso terapêutico , China/epidemiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Seizure ; 66: 70-75, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30807902

RESUMO

PURPOSE: Tremor is frequently observed in patients with epilepsy (PWE), which is generally attributed to the side-effect of antiepileptic drugs (AEDs) particularly valproate (VPA) with largely unknown mechanisms. The study aimed to assess the clinical features and related factors of tremor in PWE with tremor. METHODS: PWE with tremor and a control group of age- and sex-matched PWE without tremor were enrolled. Detailed demographic and clinical information for each individual was recorded. PWE with tremor were evaluated by The Clinical Rating Scale for Tremor (CRST) and Tremor Related Activities of Daily Living (TRADL) questionnaire. RESULTS: 132 individuals were enrolled, which including sixty-six (36 males) PWE with tremor with mean age of 33 years and epilepsy duration of 12.5 years. Tremor was postural in all, with median duration of four and one year from diagnosis and AED treatment to the onset of tremor respectively. The upper limbs were predominantly affected. VPA had been used in 62 (93.9%) PWE with tremor compared to 31 (47.0%) PWE without tremor (P < 0.001). The total CRST score was significantly associated with epilepsy duration and maximum VPA dosage (B = 0.30, p < 0.001; B = 0.32, p = 0.013). Patients with VPA dosage over 17.05 mg/kg/d might be more vulnerable to develop tremor. CONCLUSIONS: PWE with tremor were more frequently treated with VPA, however, tremor was mild in most without any functional impairment. Epilepsy duration and maximum VPA dosage were important factors of tremor severity, suggesting mechanisms underlying tremor in PWE may be an elaborate interplay of AEDs and disease itself.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/complicações , Tremor/etiologia , Atividades Cotidianas , Adulto , Anticonvulsivantes/uso terapêutico , Estudos de Casos e Controles , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Tremor/psicologia , Extremidade Superior/fisiopatologia , Ácido Valproico/efeitos adversos , Adulto Jovem
14.
Plant Physiol ; 180(1): 342-355, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30765479

RESUMO

Histone deacetylases remove acetyl groups from histone proteins and play important roles in many genomic processes. How histone deacetylases perform specialized molecular and biological functions in plants is poorly understood. Here, we identify HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 15 (HOS15) as a core member of the Arabidopsis (Arabidopsis thaliana) HISTONE DEACETYLASE9-POWERDRESS (HDA9-PWR) complex. HOS15 immunoprecipitates with both HDA9 and PWR. Mutation of HOS15 induces histone hyperacetylation and methylation changes similar to hda9 and pwr mutants. HOS15, HDA9, and PWR are coexpressed in all organs, and mutant combinations display remarkable phenotypic resemblance and nonadditivity for organogenesis and developmental phase transitions. Ninety percent of HOS15-regulated genes are also controlled by HDA9 and PWR HDA9 binds to and directly represses 92 genes, many of which are responsive to biotic and abiotic stimuli, including a family of ethylene response factor genes. Additionally, HOS15 regulates HDA9 nuclear accumulation and chromatin association. Collectively, this study establishes that HOS15 forms a core complex with HDA9 and PWR to control gene expression and plant development.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas Cromossômicas não Histona/metabolismo , Histona Desacetilases/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas Cromossômicas não Histona/genética , Epistasia Genética , Regulação da Expressão Gênica de Plantas , Histona Desacetilases/genética , Histonas/metabolismo , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Mutação , Plantas Geneticamente Modificadas , Mapeamento de Interação de Proteínas , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Transcrição Genética
15.
Science ; 363(6423): 166-167, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30630929

RESUMO

Darwin proposed that mate choice might contribute to the evolution of cognitive abilities. An open question is whether observing the cognitive skills of an individual makes it more attractive as a mate. In this study, we demonstrated that initially less-preferred budgerigar males became preferred after females observed that these males, but not the initially preferred ones, were able to solve extractive foraging problems. This preference shift did not occur in control experiments in which females observed males with free access to food or in which females observed female demonstrators solving these extractive foraging problems. Our results suggest that direct observation of problem-solving skills increases male attractiveness and that this could contribute to the evolution of the cognitive abilities underlying such skills.


Assuntos
Cognição , Preferência de Acasalamento Animal , Melopsittacus/fisiologia , Resolução de Problemas , Animais , Comportamento Apetitivo , Proteínas Quinases Dependentes de GMP Cíclico , Proteínas de Drosophila , Feminino , Masculino
16.
Eur J Hum Genet ; 27(5): 747-759, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30664714

RESUMO

CYFIP2, encoding the evolutionary highly conserved cytoplasmic FMRP interacting protein 2, has previously been proposed as a candidate gene for intellectual disability and autism because of its important role linking FMRP-dependent transcription regulation and actin polymerization via the WAVE regulatory complex (WRC). Recently, de novo variants affecting the amino acid p.Arg87 of CYFIP2 were reported in four individuals with epileptic encephalopathy. We here report 12 independent patients harboring a variety of de novo variants in CYFIP2 broadening the molecular and clinical spectrum of a novel CYFIP2-related neurodevelopmental disorder. Using trio whole-exome or -genome sequencing, we identified 12 independent patients carrying a total of eight distinct de novo variants in CYFIP2 with a shared phenotype of intellectual disability, seizures, and muscular hypotonia. We detected seven different missense variants, of which two occurred recurrently (p.(Arg87Cys) and p.(Ile664Met)), and a splice donor variant in the last intron for which we showed exon skipping in the transcript. The latter is expected to escape nonsense-mediated mRNA decay resulting in a truncated protein. Despite the large spacing in the primary structure, the variants spatially cluster in the tertiary structure and are all predicted to weaken the interaction with WAVE1 or NCKAP1 of the actin polymerization regulating WRC-complex. Preliminary genotype-phenotype correlation indicates a profound phenotype in p.Arg87 substitutions and a more variable phenotype in other alterations. This study evidenced a variety of de novo variants in CYFIP2 as a novel cause of mostly severe intellectual disability with seizures and muscular hypotonia.

17.
Bone ; 121: 163-171, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30599297

RESUMO

Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with "corner fractures" (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of "corner fractures". An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extracellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and "corner fracture" appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30616141

RESUMO

The pupal endoparasitoid wasp Trichopria drosophilae (Hymenoptera: Diapriidae) plays an important role in biological control of many frugivorous fruit fly species including Drosophila suzukii, a well-known invasive pest. Here, we report the transcriptomes of T. drosophilae among different developmental stages. A total of 601,148,438 high-quality reads were obtained and de novo assembled into 187,704 unigenes with an average length of 1096 bp. Among them, 21,735 unigenes were annotated into 52 Gene Ontology terms and 36,898 were assigned to 25 Cluster of Orthologous Groups categories, whereas 30,585 unigenes were mapped to 270 Kyoto Encyclopedia of Genes and Genomes different pathways. Numbers of differentially expressed genes were found through comparisons between different developmental stages. We further identified 137 cuticular protein genes (CPs) from T. drosophilae transcriptome, including 59 from CPR family, 2 from Tweedle family, 1 from CPF family, 46 from CPAP family, and 29 from other CP families. We analyzed expression patterns of the CPs at different developmental stages of T. drosophilae, and found some stage-specific CPs. Quantitative real-time PCR results confirmed RNA sequencing findings based on the relative expression levels of eight randomly selected CPs. This study provides a valuable transcriptomic resource for a comprehensive understanding of the development and physiology of T. drosophilae, and will help to improve their parasitism efficiency for biological control purposes.


Assuntos
Escamas de Animais/metabolismo , Genes de Insetos , Himenópteros/crescimento & desenvolvimento , Himenópteros/genética , Transcriptoma , Animais , Reação em Cadeia da Polimerase em Tempo Real
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 211: 356-362, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30593945

RESUMO

Techniques to inspect and analyze human colorectal cancer cell lines by using terahertz time-domain attenuated total reflection spectroscopy (THz TD-ATR) were investigated. The characteristics of THz absorption spectra of two colorectal cancer cell lines DLD-1 and HT-29 in aqueous solutions with different concentrations were studied. Different spectral features were observed compared to normal cell line. Identification results based on different parameters including absorption coefficient, refractive index, real and imaginary parts of complex permittivity, dielectric loss tangent were discussed. This research may be promising for quick and instant inspection of liquid samples by using THz time-domain spectroscopy in medical applications.


Assuntos
Adenocarcinoma/química , Neoplasias do Colo/química , Espectroscopia Terahertz/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Células HT29 , Humanos , Camundongos , Células NIH 3T3
20.
Front Neurol ; 9: 891, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425677

RESUMO

Background: There is limited detailed clinical information for patients with epilepsy in Tibet. This study sought to provide data about the clinical features of epilepsy in the Ganzi Tibetan Autonomous Prefecture to improve strategies for epilepsy prevention and management in this region. Methods: We reviewed the clinical record of patients with epilepsy in the Neurology Department, Ganzi Tibetan Autonomous Prefecture People's Hospital and compared the clinical features and compared it with control, from West China Hospital in Chengdu. Results: This retrospective study included 165 patients with epilepsy admitted between January 2015 and February 2018. Majority of patients (97%) in this study had active epilepsy; 28.5% had generalized onset seizures and 68.5% had focal onset seizures. Fifty-four patients had received anti-epileptic drug (AED) treatment prior to hospitalization, however, 38 (70.4%) patients took the medication irregularly. The leading etiology of this cohort was head trauma (20.6%), followed by stroke (10.9%), neurocysticercosis (7.9%), brain hydatidosis (6.7%) and tuberculous infection (5.5%). Compared with in-patients in Chengdu, epilepsy in Ganzi was more frequently caused by infection (OR = 4.216, 95% CI, 2.124-8.367), including neurocysticercosis (OR = 29.301, 95% CI, 1.727-497.167) and brain hydatidosis (OR = 24.637, 95% CI, 1.439-421.670). Conclusions: These data suggest that the control of cerebral infections, especially parasite infection, is essential for the prevention of epilepsy in the Ganzi Tibetan Autonomous Prefecture. Education of local primary doctors and patients about the literacy of epilepsy will enable better management of epilepsy in this population.

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