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BACKGROUND: Modic changes (MCs), vertebral end plate and bone marrow damage observed by magnetic resonance imaging, are an independent risk factor for low back pain. The compositions of and interaction between microbiota and metabolites in the lumbar cartilaginous end plates (LCEPs) of patients with MCs have not been identified. METHODS: Patients with lumbar disc degeneration who were undergoing lumbar spinal fusion surgery were recruited between April 2020 and April 2021. LCEPs were collected for 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC/MS)-based targeted metabolomic profiling. Of the 54 patients recruited, 24 had no MCs and 30 had changes classified as Modic type 2 or 3. The primary goal was to identify specific genera of microbiota associated with MCs, and secondary goals included investigating differences in metabolites between patients with and without MCs and exploring the correlation between these metabolites and microorganisms. RESULTS: Investigation of the microbiota community structure revealed that both alpha diversity and beta diversity were significantly different between patients with and without MCs, and the abundances of 26 genera were significantly different between these 2 groups. Metabolomic analysis revealed that 26 metabolites were significantly different between the 2 groups. The unsaturated fatty acid pathway was found to be the main pathway related to MCs. Multiomic correlation analysis suggested that Caulobacteraceae (unclassified) and Mycobacterium, Clostridium, Blautia, and Bifidobacterium at the genus level were linked to dysregulation of fatty acid metabolism, contributing to the pathogenesis of MCs. CONCLUSIONS: Our study represents a foundational effort to examine the landscape of the microbiota and metabolites in patients with MCs, informing future studies on the pathogenesis of and targeted therapy for MCs. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Glycerol-3-phosphate acyltransferase GPAT9 catalyzes the first acylation of glycerol-3-phosphate (G3P), a committed step of glycerolipid synthesis in Arabidopsis. The role of GPAT9 in Brassica napus remains to be elucidated. Here, we identified four orthologs of GPAT9 and found that BnaGPAT9 encoded by BnaC01T0014600WE is a predominant isoform and promotes seed oil accumulation and eukaryotic galactolipid synthesis in Brassica napus. BnaGPAT9 is highly expressed in developing seeds and is localized in the endoplasmic reticulum (ER). Ectopic expression of BnaGPAT9 in E. coli and siliques of Brassica napus enhanced phosphatidic acid (PA) production. Overexpression of BnaGPAT9 enhanced seed oil accumulation resulting from increased 18:2-fatty acid. Lipid profiling in developing seeds showed that overexpression of BnaGPAT9 led to decreased phosphatidylcholine (PC) and a corresponding increase in phosphatidylethanolamine (PE), implying that BnaGPAT9 promotes PC flux to storage triacylglycerol (TAG). Furthermore, overexpression of BnaGPAT9 also enhanced eukaryotic galactolipids including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG), with increased 36:6-MGDG and 36:6-DGDG, and decreased 34:6-MGDG in developing seeds. Collectively, these results suggest that ER-localized BnaGPAT9 promotes PA production, thereby enhancing seed oil accumulation and eukaryotic galactolipid biosynthesis in Brassica napus.
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Arabidopsis , Brassica napus , Brassica napus/genética , Brassica napus/metabolismo , Galactolipídeos/metabolismo , Glicerol/metabolismo , Escherichia coli/metabolismo , Glicerol-3-Fosfato O-Aciltransferase/genética , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Sementes/genética , Sementes/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ácidos Fosfatídicos/metabolismo , Óleos de Plantas/metabolismo , Fosfatos/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Dry eye disease (DED) is a common multi-factorial disease that is characterized by tear film instability. Diquafosol tetrasodium (DQS), an ophthalmic solution, has been shown to be beneficial in the treatment of DED. The goal of this study was to provide an update on the safety and efficacy of topical 3% DQS in treating DED patients. A thorough search for all the published randomized controlled trials (RCTs) up to March 31, 2022 in CENTRAL, PubMed, Scopus, and Google Scholar databases was performed. Data were reported as standardized mean difference (SMD) with 95% confidence interval (CI). Modified Jadad scale was used for sensitivity analysis. Funnel plot and Egger's regression test assessed the publication bias. Fourteen RCTs evaluating the safety and efficacy of topical 3% DQS treatment in DED patients were included. Eight included RCTs reported data on the DED after cataract surgery. Overall findings suggest that 3% DQS treatment in DED patients was associated with signiï¬cantly better improvement at 4 weeks in tear breakup time, Schirmer test, ï¬uorescein staining scores, and Rose Bengal staining score as compared to patients treated with others eye drops including artificial tears or 01% sodium hyaluronate. However, no significant difference in ocular surface disease index was observed. Our findings suggest that 3% DQS treatment is safer and had a superior efficacy compared to artificial tears or sodium hyaluronate for treating DED in general and DED after cataract surgery.
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Síndromes do Olho Seco , Soluções Oftálmicas , Polifosfatos , Humanos , Síndromes do Olho Seco/tratamento farmacológico , Ácido Hialurônico , Lubrificantes Oftálmicos , Soluções Oftálmicas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Lágrimas , Extração de Catarata , Polifosfatos/uso terapêutico , Nucleotídeos de Uracila/uso terapêuticoRESUMO
The impacts of lysine demethylase 1B (KDM1B) have been probed in multiple diseases, but the effects of KDM1B on SS remained obscure. The study aimed to unravel the efficiency of KDM1B on SS progression via the paired box 6 (PAX6)/clusterin (CLU) axis. NODB10. H2b mice were selected to establish the SS model. KDM1B, Pax6, and CLU expression in SS mice was assessed. Adeno-associated viruses carrying KDM1B, Pax6, and CLU were injected into the SS mice to detect tear secretion, epithelium corneal fluorescein staining scores, and levels of specific markers of lacrimal gland epithelial cells, neurotransmitter receptors that induce secretion from the lacrimal gland, and genes encoding normal tear components. The relation among KDM1B, Pax6, and CLU was examined. The rescue experiments were conducted for verifying the interaction among KDM1B, Pax6, and CLU. KDM1B expression was elevated, while Pax6 and CLU levels were decreased in the lacrimal gland tissues of SS mouse models. KDM1B decrement and Pax6 augmentation improved tear secretion, reduced corneal fluorescein staining score, decreased levels of specific markers of lacrimal gland epithelial cells, and increased levels of neurotransmitter receptors that induce secretion from the lacrimal gland and genes encoding normal tear components. KDM1D suppressed Pax6 expression by mediating H3K4me2 demethylation. Pax6 promoted the expression of CLU at the transcriptional level by binding to the CLU promoter. Silencing of Pax6 or CLU could reverse the effects of KDM1B reduction on improving the tear secretion disorder of SS mice. Silencing KDM1B mitigates the tear secretion disorder of SS mice via modulating the Pax6/CLU axis.
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Síndrome de Sjogren , Animais , Camundongos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genética , Síndrome de Sjogren/metabolismo , Lisina , Clusterina , Camundongos Endogâmicos NOD , Fluoresceínas , Fator de Transcrição PAX6/genéticaRESUMO
BACKGROUND: Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations. METHOD: Targeted next-generation sequencing (TGS) of 127 known deafness genes was performed for the 14-year-old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next-generation sequencing (TGS) of 127 existing hearing loss-related genes in a 14-year-old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed. RESULTS: Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein. CONCLUSIONS: We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.
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Miosinas , Síndromes de Usher , Humanos , Adolescente , Miosina VIIa , Linhagem , Miosinas/genética , Síndromes de Usher/genética , Sequenciamento de Nucleotídeos em Larga Escala , ChinaRESUMO
BACKGROUND: Distal arthrogryposis (DA) is comprised of a group of rare developmental disorders in muscle, characterized by multiple congenital contractures of the distal limbs. Fast skeletal muscle troponin-T (TNNT3) protein is abundantly expressed in skeletal muscle and plays an important role in DA. Missense variants in TNNT3 are associated with DA, but few studies have fully clarified its pathogenic role. METHODS: Sanger sequencing was performed in three generation of a Chinese family with DA. To determine how the p.R63C variant contributed to DA, we identified a variant in TNNT3 (NM_006757.4): c.187C>T (p.R63C). And then we investigated the effects of the arginine to cysteine substitution on the distribution pattern and the half-life of TNNT3 protein. RESULTS: The protein levels of TNNT3 in affected family members were 0.8-fold higher than that without the disorder. TNNT3 protein could be degraded by the ubiquitin-proteasome complex, and the p.R63C variant did not change TNNT3 nuclear localization, but significantly prolonged its half-life from 2.5 to 7 h, to promote its accumulation in the nucleus. CONCLUSION: The p.R63C variant increased the stability of TNNT3 and promoted nuclear accumulation, which suggested its role in DA.
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Artrogripose/genética , Mutação Puntual , Troponina T/genética , Troponina T/metabolismo , Substituição de Aminoácidos , Arginina/genética , Artrogripose/etiologia , Artrogripose/metabolismo , Estudos de Casos e Controles , Núcleo Celular/metabolismo , Criança , Cisteína/genética , Feminino , Células HEK293 , Humanos , Masculino , Gravidez , Estabilidade ProteicaRESUMO
BACKGROUND: QRFPR is a recently identified member of the G protein-coupled receptor and is an orphan receptor for 26Rfa, which plays important role in the regulation of many physiological functions. METHODS: Here, we employed whole exome sequencing (WES) to examine the patients with intellectual disability (ID) and difficulty in feeding. We performed SIFT and PolyPhen2 predictions for the variants. The structure model was built from scratch by I-TASSER. Here, results derived from a number of cell-based functional assays, including shRNA experiment, intracellular Ca2+ measurement, the expression of PI3 K-AKT-mTOR, and phosphorylation. The functional effect of QRFPR variants on PI3K-AKT-mTOR signaling was evaluated in vitro transfection experiments. RESULT: Here, we identified two QRFPR variants at c.202 T>C (p.Y68H) and c.1111C>T (p.R371W) in 2 unrelated individuals. Structural analysis revealed that p.Y68H and p.R371W variants may affect the side chain structure of adjacent amino acids causing reduced binding of QRFPR to 26Rfa. The results show that QRFPR stimulated by 26Rfa leading to the transient rise of intracellular Ca2+ . The QRFPR variations p.Y68H and p.R371 W can reduce the mobilization of intracellular Ca2+ . The phosphorylation levels of the PI3K, Akt, and mTOR were significantly up- or downregulated by QRFPR overexpression or silencing, respectively. The QRFPR variations inhibited PI3K-AKT-mTOR signaling, resulting in downregulation of p-mTOR. CONCLUSIONS: Our findings suggest that QRFPR acts as important role in neurodevelopment, and the effects of QRFPR are likely to be mediated by the Ca2+ -dependent PI3K-AKT-mTOR pathways. Importantly, these findings provide a foundation for future elucidation of GPCR-mediated signaling and the physiological implications.
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Variação Genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Sequência de Bases , Sinalização do Cálcio , Criança , Pré-Escolar , Células HEK293 , Humanos , Espaço Intracelular/metabolismo , Masculino , Modelos Moleculares , Fenótipo , Fosforilação , Estabilidade Proteica , Receptores Acoplados a Proteínas G/química , Sequenciamento do ExomaRESUMO
BACKGROUND: Koalas are infected with the koala retrovirus (KoRV) that exists as exogenous or endogenous viruses. KoRV is genetically diverse with co-infection with up to ten envelope subtypes (A-J) possible; KoRV-A is the prototype endogenous form. KoRV-B, first found in a small number of koalas with an increased leukemia prevalence at one US zoo, has been associated with other cancers and increased chlamydial disease. To better understand the molecular epidemiology of KoRV variants and the effect of increased viral loads (VLs) on transmissibility and pathogenicity we developed subtype-specific quantitative PCR (qPCR) assays and tested blood and tissue samples from koalas at US zoos (n = 78), two Australian zoos (n = 27) and wild-caught (n = 21) in Australia. We analyzed PCR results with available clinical, demographic, and pedigree data. RESULTS: All koalas were KoRV-A-infected. A small number of koalas (10.3%) at one US zoo were also infected with non-A subtypes, while a higher non-A subtype prevalence (59.3%) was found in koalas at Australian zoos. Wild koalas from one location were only infected with KoRV-A. We observed a significant association of infection and plasma VLs of non-A subtypes in koalas that died of leukemia/lymphoma and other neoplasias and report cancer diagnoses in KoRV-A-positive animals. Infection and VLs of non-A subtypes was not associated with age or sex. Transmission of non-A subtypes occurred from dam-to-offspring and likely following adult-to-adult contact, but associations with contact type were not evaluated. Brief antiretroviral treatment of one leukemic koala infected with high plasma levels of KoRV-A, -B, and -F did not affect VL or disease progression. CONCLUSIONS: Our results show a significant association of non-A KoRV infection and plasma VLs with leukemia and other cancers. Although we confirm dam-to-offspring transmission of these variants, we also show other routes are possible. Our validated qPCR assays will be useful to further understand KoRV epidemiology and its zoonotic transmission potential for humans exposed to koalas because KoRV can infect human cells.
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Gammaretrovirus/genética , Phascolarctidae/virologia , Infecções por Retroviridae/veterinária , Infecções Tumorais por Vírus/veterinária , Animais , Animais Selvagens , Animais de Zoológico , Austrália/epidemiologia , Feminino , Gammaretrovirus/classificação , Gammaretrovirus/isolamento & purificação , Gammaretrovirus/patogenicidade , Variação Genética , Masculino , Epidemiologia Molecular , Reação em Cadeia da Polimerase/veterinária , Prevalência , RNA Viral/genética , Infecções por Retroviridae/epidemiologia , Infecções por Retroviridae/transmissão , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/transmissão , Infecções Tumorais por Vírus/virologia , Estados Unidos/epidemiologia , Carga ViralRESUMO
OBJECTIVE: To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis. METHODS: Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing. RESULTS: A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2. CONCLUSION: The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.
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Artrogripose , Proteínas do Citoesqueleto/genética , Feminino , Heterozigoto , Humanos , Mutação , Linhagem , Gravidez , Diagnóstico Pré-Natal , Sequenciamento do ExomaRESUMO
BACKGROUND: Malignant pleural effusion (MPE) is common and diagnosis is often problematic. A cancer ratio (serum lactate dehydrogenases: pleural adenosine deaminase ratio) has been proposed for diagnosing MPE. However, the usefulness of this "cancer ratio" and the clinical-radiological criteria for diagnosing MPE has not been clearly determined to date. The aim of this study was to assess the performance of those parameters in the diagnosis of MPE. METHODS: We analyzed 240 patients including 120 with MPE and 120 with non-MPE (93 tuberculous and 27 parapneumonic). Patients were divided into two groups: MPE and non-MPE (eg, tuberculous and parapneumonic). We constructed two predictive models to assess the probability of MPE: (a) clinical-radiological data only and (b) a combination of clinical-radiological data, the cancer ratio, and the carcinoembryonic antigen (CEA). The performances of the predictive models were assessed using receiver operating characteristic (ROC) curves and by examining the calibration. RESULTS: The area under the ROC curves for model 1 and model 2 were excellent, 0.936 and 0.998, respectively. The overall diagnostic accuracies for model 1 and model 2 were 87.5% and 98.8%, respectively. CONCLUSION: The results confirm that both models achieved a high diagnostic accuracy for MPE; however, model 2 was superior with the addition of its simplicity of use in daily practice. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures.
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Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Antígeno Carcinoembrionário/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/sangue , Derrame Pleural Maligno/patologia , Valor Preditivo dos Testes , Curva ROC , RadiografiaAssuntos
Doenças Genéticas Ligadas ao Cromossomo X/genética , Ictiose/genética , Metaloendopeptidases/genética , Dermatopatias Genéticas/genética , Povo Asiático/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Humanos , Ictiose/diagnóstico , Masculino , Mutação de Sentido Incorreto , Linhagem , Dermatopatias Genéticas/diagnóstico , Adulto JovemRESUMO
Simian foamy viruses (SFVs) are retroviruses present in nearly all nonhuman primates (NHPs), including Old World primates (OWP) and New World primates (NWP). While all confirmed human infections with SFV are from zoonotic transmissions originating from OWP, little is known about the zoonotic transmission potential of NWP SFV. We conducted a longitudinal, prospective study of 56 workers occupationally exposed to NWP in Brazil. Plasma from these workers was tested using Western blot (WB) assays containing NWP SFV antigens. Genomic DNA from blood and buccal swabs was analyzed for the presence of proviral SFV sequences by three nested PCR tests and a new quantitative PCR assay. Exposure histories were obtained and analyzed for associations with possible SFV infection. Ten persons (18%) tested seropositive and two persons were seroindeterminate (3.6%) for NWP SFV. Six persons had seroreactivity over 2-3 years suggestive of persistent infection. All SFV NWP WB-positive workers reported at least one incident involving NWP, including six reporting NWP bites. NWP SFV viral DNA was not detected in the blood or buccal swabs from all 12 NWP SFV seroreactive workers. We also found evidence of SFV seroreversion in three workers suggestive of possible clearance of infection. Our findings suggest that NWP SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses but infection remains well-controlled resulting in latent infection and may occasionally clear.
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Infecções por Retroviridae/diagnóstico , Vírus Espumoso dos Símios/genética , Zoonoses/diagnóstico , Adulto , Animais , Antígenos Virais/imunologia , Antígenos Virais/metabolismo , Brasil , DNA Viral/sangue , DNA Viral/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/virologia , Reação em Cadeia da Polimerase , Primatas , Estudos Prospectivos , Infecções por Retroviridae/transmissão , Infecções por Retroviridae/virologia , Risco , Vírus Espumoso dos Símios/isolamento & purificação , Zoonoses/virologiaRESUMO
OBJECTIVE: To carry out mutation analysis for a Chinese family affected with Escobar syndrome. METHODS: Whole exome sequencing (WES) was employed to detect potential mutation in the proband. Suspected mutations were validated by combining clinical data and result of Sanger sequencing. RESULTS: A homozygous missense mutation c.715C>T (p.R239C) was detected in the proband and his brother who was also affected. The parents and the daughters of the proband carried the heterozygous mutation c.715C>T, while other family members did not carry the mutation. CONCLUSION: Escobar syndrome is a rare genetic disorder. WES is able to discover genetic mutation underlying this disorder and facilitate genetic counseling and prenatal diagnosis for the affected family.
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Anormalidades Múltiplas/genética , Exoma , Hipertermia Maligna/genética , Anormalidades da Pele/genética , Adulto , Povo Asiático/genética , Sequência de Bases , Análise Mutacional de DNA , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Adulto JovemRESUMO
OBJECTIVE: To analyze PKHD1 gene mutation in a family affected with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Genomic DNA was extracted from peripheral and cord blood samples obtained from the parents and the fetus. Potential mutations were identified using targeted exome sequencing and confirmed by Sanger sequencing. Pathogenicity of the mutation was analyzed using PolyPhen-2 and SIFT software. RESULTS: Compound heterozygous mutations of c.11314C>T (p.Arg3772*) and a novel missense c.889T>A (p.Cys297Ser) of the PKHD1 gene were identified in the fetus. The mother was found to have carried the c.11314C>T mutation, while the father was found to have carried the c.889T>A mutation. PolyPhen-2 and SIFT predicted that the c.889T>A mutation is probably damaging. CONCLUSION: A novel mutation in PKHD1 gene was detected in our ARPKD family. Compound heterozygous PKHD1 mutations were elucidated to be the molecular basis for the fetus affected with ARPKD, which has facilitated genetic counseling and implement of prenatal diagnosis for the family.
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Doenças Fetais/genética , Mutação , Rim Policístico Autossômico Recessivo/genética , Receptores de Superfície Celular/genética , Aborto Eugênico , Adulto , Sequência de Aminoácidos , Sequência de Bases , Análise Mutacional de DNA , Saúde da Família , Evolução Fatal , Feminino , Doenças Fetais/diagnóstico por imagem , Feto/anormalidades , Feto/metabolismo , Humanos , Masculino , Rim Policístico Autossômico Recessivo/diagnóstico por imagem , Rim Policístico Autossômico Recessivo/embriologia , Gravidez , Homologia de Sequência de Aminoácidos , Ultrassonografia Pré-Natal/métodosRESUMO
Zoonotic transmission of simian retroviruses in West-Central Africa occurring in primate hunters has resulted in pandemic spread of human immunodeficiency viruses (HIVs) and human T-lymphotropic viruses (HTLVs). While simian foamy virus (SFV) and simian T- lymphotropic virus (STLV)-like infection were reported in healthy persons exposed to nonhuman primates (NHPs) in West-Central Africa, less is known about the distribution of these viruses in Western Africa and in hospitalized populations. We serologically screened for SFV and STLV infection using 1,529 specimens collected between 1985 and 1997 from Côte d'Ivoire patients with high HIV prevalence. PCR amplification and analysis of SFV, STLV, and HIV/SIV sequences from PBMCs was used to investigate possible simian origin of infection. We confirmed SFV antibodies in three persons (0.2%), two of whom were HIV-1-infected. SFV polymerase (pol) and LTR sequences were detected in PBMC DNA available for one HIV-infected person. Phylogenetic comparisons with new SFV sequences from African guenons showed infection likely originated from a Chlorocebus sabaeus monkey endemic to Côte d'Ivoire. 4.6% of persons were HTLV seropositive and PCR testing of PBMCs from 15 HTLV seroreactive persons identified nine with HTLV-1 and one with HTLV-2 LTR sequences. Phylogenetic analysis showed that two persons had STLV-1-like infections, seven were HTLV-1, and one was an HTLV-2 infection. 310/858 (53%), 8/858 (0.93%), and 18/858 (2.1%) were HIV-1, HIV-2, and HIV-positive but undifferentiated by serology, respectively. No SIV sequences were found in persons with HIV-2 antibodies (n = 1) or with undifferentiated HIV results (n = 7). We document SFV, STLV-1-like, and dual SFV/HIV infection in Côte d'Ivoire expanding the geographic range for zoonotic simian retrovirus transmission to West Africa. These findings highlight the need to define the public health consequences of these infections. Studying dual HIV-1/SFV infections in immunocompromised populations may provide a new opportunity to better understand SFV pathogenicity and transmissibility in humans.
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Infecções por Deltaretrovirus/diagnóstico , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Infecções por Retroviridae/diagnóstico , Vírus Espumoso dos Símios/isolamento & purificação , Animais , Anticorpos Antivirais/sangue , Chlorocebus aethiops , Coinfecção , Côte d'Ivoire/epidemiologia , DNA Viral/genética , Infecções por Deltaretrovirus/epidemiologia , Infecções por Deltaretrovirus/virologia , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-2/classificação , HIV-2/genética , HIV-2/isolamento & purificação , Vírus Linfotrópico T Tipo 1 Humano/classificação , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Vírus Linfotrópico T Tipo 2 Humano/classificação , Vírus Linfotrópico T Tipo 2 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Doenças dos Macacos/diagnóstico , Doenças dos Macacos/epidemiologia , Doenças dos Macacos/virologia , Filogenia , Infecções por Retroviridae/epidemiologia , Infecções por Retroviridae/virologia , Vírus Espumoso dos Símios/classificação , Vírus Espumoso dos Símios/genéticaRESUMO
Wrinkled1 (WRI1) belongs to the APETALA2 transcription factor family; it is unique to plants and is a central regulator of oil synthesis in Arabidopsis. The effects of WRI1 on comprehensive lipid metabolism and plant development were unknown, especially in crop plants. This study found that BnWRI1 in Brassica napus accelerated flowering and enhanced oil accumulation in both seeds and leaves without leading to a visible growth inhibition. BnWRI1 decreased storage carbohydrates and increased soluble sugars to facilitate the carbon flux to lipid anabolism. BnWRI1 is localized to the nucleus and directly binds to the AW-box at proximal upstream regions of genes involved in fatty acid (FA) synthesis and lipid assembly. The overexpression (OE) of BnWRI1 resulted in the up-regulation of genes involved in glycolysis, FA synthesis, lipid assembly, and flowering. Lipid profiling revealed increased galactolipids monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and phosphatidylcholine (PC) in the leaves of OE plants, whereas it exhibited a reduced level of the galactolipids DGDG and MGDG and increased levels of PC, phosphatidylethanolamide, and oil [triacylglycerol (TAG)] in the siliques of OE plants during the early seed development stage. These results suggest that BnWRI1 is important for homeostasis among TAG, membrane lipids and sugars, and thus facilitates flowering and oil accumulation in B. napus.
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[This corrects the article on p. 1015 in vol. 6, PMID: 26635841.].
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Visfatin is identified a pro-inflammatory cytokine and its serum level is increased in various cancers. This study aimed to evaluate the prognostic value of preoperative serum visfatin level in breast cancers. Preoperative serum visfatin levels of 248 patients with breast cancer and serum visfatin levels of 100 healthy individuals and 100 benign women controls were determined using enzyme-linked immunosorbent assay. Unfavorable outcome was defined as first local recurrence, distant metastasis, second primary cancer of another organ, or death from any cause. Disease-free survival was defined as the time between surgery and the date of unfavorable outcome whichever appeared first. Overall survival was defined from surgery to death for any cause. The association of serum visfatin level with outcomes including mortality, unfavorable outcome, disease-free survival and overall survival was investigated by univariate and multivariate analyses. Preoperative serum visfatin level was substantially higher in patients than in healthy subjects and benign controls respectively. Elevated preoperative serum level of visfatin was identified an independent predictor of mortality, unfavorable outcome, disease-free survival and overall survival. Receiver operating characteristic curve analysis showed that serum level visfatin had high predictive value for mortality and unfavorable outcome. Thus, our results suggest that high preoperative serum visfatin level is associated with poor patient outcomes as well as may play a role as prognostic biomarker in breast cancer survival.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Citocinas/sangue , Nicotinamida Fosforribosiltransferase/sangue , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , China , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Resultado do TratamentoRESUMO
Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population.
Assuntos
Animais de Zoológico , Neoplasias/virologia , Retroviridae/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , DNA Viral , Humanos , Marsupiais , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Retroviridae/genética , Retroviridae/patogenicidade , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Estados UnidosRESUMO
Proapoptotic Bcl-2 homology 3-only protein Bim plays an important role in Bax/Bak-mediated cytochrome c release and apoptosis. Here, we provide evidence for a novel prosurvival function of Bim in cancer cells. Bim was constitutively overexpressed in multiple prostate and breast cancer cells as well as in primary tumor cells. Quantitative real time PCR analysis showed that Bim was transcriptionally up-regulated. We have identified eight endogenous E2F1-binding sites on the Bim promoter using in silico analysis. Luciferase assay demonstrated that Bim expression was E2F1-dependent as mutation of the E2F1-binding sites on the Bim promoter inhibited luciferase activities. In support, E2F1 silencing led to the loss of Bim expression in cancer cells. Bim primarily localized to mitochondrial and cytoskeleton-associated fractions. Bim silencing or microinjection of anti-Bim antibodies into the cell cytoplasm resulted in cell rounding, detachment, and subsequent apoptosis. We observed up-regulation of prosurvival proteins Bcl-xL and Mcl-1, which sequester Bim in cancer cells. In addition, a phosphorylated form of Bim was also elevated in cancer cells. These findings suggest that the constitutively overexpressed Bim may function as a prosurvival molecule in epithelial cancer cells, and phosphorylation and association with Bcl-xL/Mcl-1 block its proapoptotic functions.