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1.
Int J Biol Macromol ; 155: 50-60, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32220641

RESUMO

Salinity represents a critical environmental factor for fishes, and it can directly influence their survival. Transcriptomic analysis at the gene expression level has been extensively conducted to identify functional genes or pathways involved in salinity adaptation in numerous euryhaline fishes. However, the post-transcriptional regulation mechanism in response to salinity changes remains largely unknown. Alternative splicing (AS), the main mechanism accounting for the complexity of the transcriptome and proteome in eukaryotes, plays essential roles in determining organismal responses to environmental changes. In this study, RNA-Seq datasets were used to examine the AS profiles in spotted sea bass (Lateolabrax maculatus), a typical euryhaline fish species. The results showed that 8618 AS events were identified in spotted sea bass. Furthermore, a total of 501 and 162 differential alternative splicing (DAS) events were characterized in the gill and liver under low- and high-salinity environments, respectively. Based on GO enrichment results, DAS genes in both the gill and liver were commonly enriched in 8 GO terms, and their biological functions were implicated in many stages of gene expression regulation, including transcriptional regulation and post-transcriptional regulation. Sanger sequencing and qPCR validations provided additional evidence to ensure the accuracy and reliability of our bioinformatic results. This is the first comprehensive view of AS in response to salinity changes in fish species, providing insights into the post-regulatory molecular mechanisms of euryhaline fishes in salinity adaptation.

2.
Front Genet ; 10: 1126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803231

RESUMO

Transcriptome complexity plays crucial roles in regulating the biological functions of eukaryotes. Except for functional genes, alternative splicing and fusion transcripts produce a vast expansion of transcriptome diversity. In this study, we applied PacBio single-molecule long-read sequencing technology to unveil the whole transcriptome landscape of Lateolabrax maculatus. We obtained 28,809 high-quality non-redundant transcripts, including 18,280 novel isoforms covering 8,961 annotated gene loci within the current reference genome and 3,172 novel isoforms. A total of 10,249 AS events were detected, and intron retention was the predominant AS event. In addition, 1,359 alternative polyadenylation events, 3,112 lncRNAs, 29,609 SSRs, 365 fusion transcripts, and 1,194 transcription factors were identified in this study. Furthermore, we performed RNA-Seq analysis combined with Iso-Seq results to investigate salinity regulation mechanism at the transcripts level. A total of 518 transcripts were differentially expressed, which were further divided into 8 functional groups. Notably, transcripts from the same genes exhibited similar or opposite expression patterns. Our study provides a comprehensive view of the transcriptome complexity in L. maculatus, which significantly improves current gene models. Moreover, the diversity of the expression patterns of transcripts may enhance the understanding of salinity regulatory mechanism in L. maculatus and other euryhaline teleosts.

3.
Fish Shellfish Immunol ; 92: 111-118, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176005

RESUMO

Apolipoproteins (Apos), which are the protein components of plasma lipoproteins, play important roles in lipid transport in vertebrates. It has been demonstrated that in teleosts, several Apos display antimicrobial activity and play crucial roles in innate immunity. Despite their importance, apo genes have not been systematically characterized in many aquaculture fish species. In our study, a complete set of 23 apo genes was identified and annotated from spotted sea bass (Lateolabrax maculatus). Phylogenetic and homology analyses provided evidence for their annotation and evolutionary relationships. To investigate their potential roles in the immune response, the expression patterns of 23 apo genes were determined in the liver and intestine by qRT-PCR after Vibrio harveyi infection. After infection, a total of 20 differentially expressed apo genes were observed, and their expression profiles varied among the genes and tissues. 5 apo genes (apoA1, apoA4a.1, apoC2, apoF and apoO) were dramatically induced or suppressed (log2 fold change >4, P < 0.05), suggesting their involvement in the immune response of spotted sea bass. Our study provides a valuable foundation for future studies aimed at uncovering the specific roles of each apo gene during bacterial infection in spotted sea bass and other teleost species.


Assuntos
Apolipoproteínas/genética , Apolipoproteínas/imunologia , Bass/genética , Bass/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Animais , Apolipoproteínas/química , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Família Multigênica/imunologia , Filogenia , Transcriptoma , Vibrio/fisiologia , Vibrioses/imunologia , Vibrioses/veterinária
4.
Anal Chem ; 91(9): 5499-5503, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30986341

RESUMO

We demonstrate a novel optomechanical synchronization method to achieve ultrahigh-contrast time-gated fluorescence imaging using live zebrafish as models. Silicon quantum dot nanoparticles (SiQDNPs) with photoluminescence lifetime of about 16 µs were used as the long-lived probes to enable background autofluorescence removal and multiplexing through time-gating. A continuous-wave 405 nm laser as the excitation source was focused on a rotating optical chopper on which the emission light beam obtained from an inverted fluorescence microscope was also focused but with a phase difference such that in a short delay after the excitation laser is blocked, the emission light beam passes through the optical chopper, initiating the image acquisition by a conventional sensor. Both excitation and detection time windows were synchronized by one optical chopper, eliminating the need for pulsed light source and image intensifier which is often used as ultrafast optical shutter. Through use of the cost-effective time-gating method, nearly all background autofluorescence emitted from the yolk sac of a zebrafish embryo microinjected with the SiQDNPs was removed, leading to a 45-fold increase in signal-to-background ratio. Furthermore, two kinds of fluorescence signals emitted from the microinjected SiQDNPs and the intrinsic green fluorescent protein of transgenic zebrafish larvae can be clearly separated through time-gating.

5.
Int J Biol Macromol ; 118(Pt B): 1406-1413, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29959994

RESUMO

Popillia japonica is a harmful pest with a wide range of hosts, presenting particular dangers to golf courses, lawns, and pastures. Very limited molecular data for Po. japonica are available in GenBank, including only some partial nuclear gene or mitochondrial gene sequences, and acquiring more molecular information is urgent for studying the diagnosis of infestation, phylogeny, and evolution of this beetle. Herein, we characterize the complete mitochondrial genome of Po. japonica using next-generation sequencing and describe its structural features. The circular mitochondrial genome of Po. japonica is 16,541 bp in size, containing thirteen protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), twenty-two transfer RNA genes (tRNAs), and a control region. The base composition of the whole mitochondrial genome of Po. japonica is 39.00%, 9.50%, 14.80%, and 36.70% for A, G, C, and T, respectively, demonstrating high A + T content (75.70%). Phylogenetic relationships of the superfamily Scarabaeoidea show that Po. japonica and Protaetia brevitarsis form in a clade that is a sister group to Rhopaea magnicornis and Polyphylla laticollis from Melolonthinae. Cheirotonus jansoni from Melolonthinae is a sister group with Po. japonica, Protaetia brevitarsis, Rhopaea magnicornis and Polyphylla laticollis, indicating that Melolonthinae is a polyphyletic group. This is the first report of a complete mitochondrial genome of Po. japonica and it will contribute to further studies of infestation diagnosis, phylogeny, and evolution of Scarabaeoidea.


Assuntos
Besouros/genética , Genoma Mitocondrial/genética , Filogenia , Animais , Composição de Bases , Sequência de Bases , DNA Intergênico/genética , Genômica
6.
Sensors (Basel) ; 17(6)2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28587116

RESUMO

In this work, a beat-frequency encoded fiber laser hydrophone is developed for high-resolution acoustic detection by using an elastic corrugated diaphragm. The diaphragm is center-supported by the fiber. Incident acoustic waves deform the diaphragm and induce a concentrated lateral load on the laser cavity. The acoustically induced perturbation changes local optical phases and frequency-modulates the radio-frequency beat signal between two orthogonal lasing modes of the cavity. Theoretical analysis reveals that a higher corrugation-depth/thickness ratio or larger diaphragm area can provide higher transduction efficiency. The experimentally achieved average sensitivity in beat-frequency variation is 185.7 kHz/Pa over a bandwidth of 1 kHz. The detection capability can be enhanced by shortening the cavity length to enhance the signal-to-noise ratio. The minimum detectable acoustic pressure reaches 74 µPa/Hz1/2 at 1 kHz, which is comparable to the zeroth order sea noise.

7.
Sci Rep ; 6: 28145, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27329698

RESUMO

MK2 activation by p38 MAPK selectively induces inflammation in various diseases. We determined if a MK2 inhibitor (MK2i), improves cornea wound healing by inhibiting inflammation caused by burning rat corneas with alkali. Our study, for the first time, demonstrated that MK2i inhibited alkali burn-induced MK2 activation as well as rises in inflammation based on: a) blunting rises in inflammatory index, inflammatory cell infiltration, ED1(+) macrophage and PMN(+) neutrophil infiltration; b) suppressing IL-6 and IL-1ß gene expression along with those of macrophage inflammatory protein-1α (MIP-1α), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); c) reducing angiogenic gene expression levels and neovascularization (NV) whereas anti-angiogenic PEDF levels increased. In addition, this study found that MK2i did not affect human corneal epithelial cell (HCEC) proliferation and migration and had no detectable side effects on ocular surface integrity. Taken together, MK2i selectively inhibited alkali burn-induced corneal inflammation by blocking MK2 activation, these effects have clinical relevance in the treatment of inflammation related ocular surface diseases.


Assuntos
Queimaduras Químicas/patologia , Córnea/efeitos dos fármacos , Inflamação/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Álcalis/toxicidade , Animais , Queimaduras Químicas/tratamento farmacológico , Queimaduras Químicas/etiologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismo , Córnea/metabolismo , Córnea/patologia , Humanos , Inflamação/patologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
8.
Zhonghua Yan Ke Za Zhi ; 51(9): 647-54, 2015 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-26693648

RESUMO

OBJECTIVE: To develop and assess a new dry eye questionnaire applicable to the Chinese population. METHODS: Based on literature review and clinical practice, a dry eye questionnaire was developed and optimized to apply to Chinese dry eye patients in the language expression and culture background. Participants (78 patients with dry eye and 82 controls) completed the dry eye questionnaire and the ocular surface disease index (OSDI) questionnaire, and ophthalmic examinations were performed, including slit lamp examination, tear breakup time, fluorescein staining, Schirmer I test and meibomian gland assessment. The original questionnaire was optimized with factor analysis according to the answers from respondents and clinical evaluations. The Cronbach α and intraclass correlation coefficient (ICC) were used to evaluate the internal consistency reliability and test-retest reliability. Factor analysis was used to assess the construct validity, concurrent validity was obtained by Spearman correlation analysis, and discriminant validity was obtained by ANOVA and Wilcoxon rank sum test. Receiver operator characteristics curves were generated to identify the sensitivity and specificity of each questionnaire for diagnosis of dry eye. RESULTS: The questionnaire was optimized to 12 items by factor analysis. The response rate from respondents to the dry eye questionnaire and the OSDI was 100% and 91.25%, respectively. The Cronbachαof the dry eye questionnaire and the OSDI was 0.794 and 0.925, respectively, whilst the ICC of both questionnaires was 0.99, indicating good to excellent reliability. The factor analysis suggested that these two questionnaires had good construct validity. The Spearman correlation analysis indicated that the dry eye questionnaire score correlated positively with the OSDI score (r = 0.812, P < 0.01) and had a greater correlation relationship with the clinical evaluations compared with the OSDI score (r for each was 0.613 and 0.605, P < 0.01). The discriminant validity analysis suggested that there was significant difference in the dry eye questionnaire score between the dry eye group and non-dry eye group (P < 0.01). When the dry eye questionnaire score of 7 was used as the diagnostic threshold, the sensitivity and specificity were 83.33% and 70.73%, respectively, and the area under roc curve was 0.814, which was higher than 0.772 of the OSDI (P < 0.01). CONCLUSION: The dry eye questionnaire we developed is applicable to the Chinese population with Chinese culture characteristics, high reliability, validity, specificity, and sensitivity, and holds a better diagnostic value than the OSDI for Chinese patients with dry eye.


Assuntos
Síndromes do Olho Seco/diagnóstico , Inquéritos e Questionários , Grupo com Ancestrais do Continente Asiático , China , Humanos , Idioma , Glândulas Tarsais , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Lágrimas
9.
PLoS One ; 10(10): e0141144, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495845

RESUMO

Myopia incidence in China is rapidly becoming a very serious sight compromising problem in a large segment of the general population. Therefore, delineating the underlying mechanisms leading to myopia will markedly lessen the likelihood of other sight compromising complications. In this regard, there is some evidence that patients afflicted with familial adenomatous polyposis (FAP), havean adenomatous polyposis coli (APC) mutation and a higher incidence of myopia. To clarify this possible association, we determined whether the changes in pertinent biometric and biochemical parameters underlying postnatal refractive error development in APCMin mice are relevant for gaining insight into the pathogenesis of this disease in humans. The refraction and biometrics in APCMin mice and age-matched wild-type (WT) littermates between postnatal days P28 and P84 were examined with eccentric infrared photorefraction (EIR) and customized optical coherence tomography (OCT). Compared with WT littermates, the APCMin mutated mice developed myopia (average -4.64 D) on P84 which was associated with increased vitreous chamber depth (VCD). Furthermore, retinal and scleral changes appear in these mice along with: 1) axial length shortening; 2) increased retinal cell proliferation; 3) and decreased tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of DA synthesis. Scleral collagen fibril diameters became heterogeneous and irregularly organized in the APCMin mice. Western blot analysis showed that scleral alpha-1 type I collagen (col1α1) expression also decreased whereas MMP2 and MMP9 mRNA expression was invariant. These results indicate that defective APC gene function promotes refractive error development. By characterizing in APCMin mice ocular developmental changes, this approach provides novel insight into underlying pathophysiological mechanisms contributing to human myopia development.


Assuntos
Proteína da Polipose Adenomatosa do Colo/genética , Miopia/genética , Retina/metabolismo , Esclera/metabolismo , Proteína da Polipose Adenomatosa do Colo/metabolismo , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Knockout , Miopia/metabolismo , Miopia/patologia , Refração Ocular , Retina/patologia , Esclera/patologia , Tomografia de Coerência Óptica , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Visão Ocular , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia
10.
Genet Sel Evol ; 47: 13, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25885894

RESUMO

BACKGROUND: The reliability of whole-genome prediction models (WGP) based on using high-density single nucleotide polymorphism (SNP) panels critically depends on proper specification of key hyperparameters. A currently popular WGP model labeled BayesB specifies a hyperparameter π, that is `loosely used to describe the proportion of SNPs that are in linkage disequilibrium (LD) with causal variants. The remaining markers are specified to be random draws from a Student t distribution with key hyperparameters being degrees of freedom v and scale s(2). METHODS: We consider three alternative Markov chain Monte Carlo (MCMC) approaches based on the use of Metropolis-Hastings (MH) to estimate these key hyperparameters. The first approach, termed DFMH, is based on a previously published strategy for which s(2) is drawn by a Gibbs step and v is drawn by a MH step. The second strategy, termed UNIMH, substitutes MH for Gibbs when drawing s(2) and further collapses or marginalizes the full conditional density of v. The third strategy, termed BIVMH, is based on jointly drawing the two hyperparameters in a bivariate MH step. We also tested the effect of misspecification of s(2) for its effect on accuracy of genomic estimated breeding values (GEBV), yet allowing for inference on the other hyperparameters. RESULTS: The UNIMH and BIVMH strategies had significantly greater (P < 0.05) computational efficiencies for estimating v and s(2) than DFMH in BayesA (π = 1) and BayesB implementations. We drew similar conclusions based on an analysis of the public domain heterogeneous stock mice data. We also determined significant drops (P < 0.01) in accuracies of GEBV under BayesA by overspecifying s(2), whereas BayesB was more robust to such misspecifications. However, understating s(2) was compensated by counterbalancing inferences on v in BayesA and BayesB, and on π in BayesB. CONCLUSIONS: Sampling strategies based solely on MH updates of v and s(2), and collapsed representations of full conditional densities can improve the computational efficiency of MCMC relative to the use of Gibbs updates. We believe that proper inferences on s(2), v and π are vital to ensure that the accuracy of GEBV is maximized when using parametric WGP models.


Assuntos
Teorema de Bayes , Simulação por Computador , Genoma , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Algoritmos , Animais , Genoma/genética , Genômica , Desequilíbrio de Ligação/genética , Cadeias de Markov , Camundongos , Método de Monte Carlo , Locos de Características Quantitativas , Reprodutibilidade dos Testes
11.
Chin Med J (Engl) ; 127(13): 2407-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24985574

RESUMO

BACKGROUND: Dry eye is a multifactorial disease of the tears and the ocular surface. This study aimed to investigate the clinical efficacy of a non-steroidal anti-inflammatory drug, pranoprofen, in the treatment of dry eye. METHODS: It is a prospective, multi-center, randomized, controlled, parallel group study. One hundred and fifteen patients with mild to moderate dry eye disease (55-60 in each treatment group) participated in this multi-center study. Patients were randomly administered with eyedrops containing 0.1% pranoprofen (PRA) plus 0.1% sodium hyaluronate (SH) or SH only, three times daily for 28 days, followed by a 1-week after treatment observation. Dry eye symptom score (DESS), fluorescein corneal staining (FLCS), tear break-up time (TBUT), and Shirmer 1 tear test (ST1, without anesthesia) were evaluated or conducted before treatment and at each study visit. Conjunctival impression cytology was taken from the patients treated with PRA plus SH before and after treatment and real-time polymerase chain reaction (RT-PCR) was performed to detect the changes of human leukocyte antigen DR (HLA-DR) and intercellular adhesion molecule 1 (ICAM-1). RESULTS: Patients treated with PRA plus SH showed gradual improvements of DESS, FLCS, and TBUT. Between-group comparisons of FLCS and TBUT have statistically significant differences from day 14. Good tolerance with no severe adverse events was found in both groups. Patients treated with PRA plus SH had a reduced expression level of HLA-DR and were statistically different after 28 days of therapy. CONCLUSIONS: The application of PRA at a dose of 0.1% was well tolerated and benefited to the patients with mild to moderate dry eye disease. The underlying mechanism of its efficacy may be associated with the reduction of inflammatory factors of conjunctival epithelial cells.


Assuntos
Benzopiranos/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Soluções Oftálmicas/uso terapêutico , Propionatos/uso terapêutico , Adulto , Humanos , Pessoa de Meia-Idade
12.
Invest Ophthalmol Vis Sci ; 55(5): 2963-74, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24722696

RESUMO

PURPOSE: We investigated the therapeutic effects and underlying mechanisms of topical doxycycline in a benzalkonium chloride (BAC)-induced mouse dry eye model. METHODS: Eye drops containing 0.025%, 0.1% doxycycline or solvent were administered to a BAC-induced dry eye model four times daily. The clinical evaluations, including tear break-up time (BUT), fluorescein staining, inflammatory index, and tear volume, were performed on days 0, 1, 4, 7, and 10. Global specimens were collected on day 10 and processed for immunofluorescent staining, TUNEL, and periodic acid-Schiff assay. The levels of inflammatory mediators in the corneas were determined by real-time PCR. The total and phosphorylated nuclear factor-κB (NF-κB) were detected by Western blot. RESULTS: Both 0.025% and 0.1% doxycycline treatments resulted in increased BUT, lower fluorescein staining scores, and inflammatory index on days 4, 7, and 10, while no significant change in tear volume was observed. The 0.1% doxycycline-treated group showed more improvements in decreasing fluorescein staining scores, increasing Ki-67-positive cells, and decreasing TUNEL- and keratin-10-positive cells than other groups. The mucin-filled goblet cells in conjunctivas were increased, and the expression of CD11b and levels of matrix metalloproteinase-9, IL-1ß, IL-6, TNF-α, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant in corneas were decreased in both doxycycline-treated groups. In addition, doxycycline significantly reduced the phosphorylation of NF-κB activated in the BAC-treated corneas. CONCLUSIONS: Topical doxycycline showed clinical improvements and alleviated ocular surface inflammation on BAC-induced mouse dry eye, suggesting a potential as an anti-inflammatory agent in the clinical treatment of dry eye.


Assuntos
Antibacterianos/administração & dosagem , Doxiciclina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Administração Tópica , Animais , Apoptose/efeitos dos fármacos , Compostos de Benzalcônio , Proliferação de Células/efeitos dos fármacos , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/patologia , Células Caliciformes/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/efeitos dos fármacos
13.
Zhonghua Yan Ke Za Zhi ; 49(10): 865-8, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24433685

RESUMO

In the past twenty years, with the rapid development of dry eye research in China, significant progresses have been achieved and there has been a remarkable improvement in diagnostic rate and clinical outcomes. Publication and popularization of the clinical diagnosis and treatment recommendations for dry eye from consensus of expert advice provides criteria for clinical work of dry eye. There has still been a significant gap between our research and world's advanced level in dry eye, therefore clinical investigations of high level will be intensively promoted to reveal the epidemiologic and clinical characteristics of dry eye populations in China, and establish the diagnostic criteria for Chinese patients, develop the clinical research on dry eye drugs and home-made clinical devices. Based on evidence-based research evidences, criteria for diagnosis and treatment of dry eye will be established and the clinical investigation of dry eye will be developed to reach the world's advanced level.


Assuntos
Síndromes do Olho Seco , Pesquisa Biomédica , China , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/terapia , Humanos
14.
Genetics ; 190(4): 1491-501, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22135352

RESUMO

Hierarchical mixed effects models have been demonstrated to be powerful for predicting genomic merit of livestock and plants, on the basis of high-density single-nucleotide polymorphism (SNP) marker panels, and their use is being increasingly advocated for genomic predictions in human health. Two particularly popular approaches, labeled BayesA and BayesB, are based on specifying all SNP-associated effects to be independent of each other. BayesB extends BayesA by allowing a large proportion of SNP markers to be associated with null effects. We further extend these two models to specify SNP effects as being spatially correlated due to the chromosomally proximal effects of causal variants. These two models, that we respectively dub as ante-BayesA and ante-BayesB, are based on a first-order nonstationary antedependence specification between SNP effects. In a simulation study involving 20 replicate data sets, each analyzed at six different SNP marker densities with average LD levels ranging from r(2) = 0.15 to 0.31, the antedependence methods had significantly (P < 0.01) higher accuracies than their corresponding classical counterparts at higher LD levels (r(2) > 0. 24) with differences exceeding 3%. A cross-validation study was also conducted on the heterogeneous stock mice data resource (http://mus.well.ox.ac.uk/mouse/HS/) using 6-week body weights as the phenotype. The antedependence methods increased cross-validation prediction accuracies by up to 3.6% compared to their classical counterparts (P < 0.001). Finally, we applied our method to other benchmark data sets and demonstrated that the antedependence methods were more accurate than their classical counterparts for genomic predictions, even for individuals several generations beyond the training data.


Assuntos
Teorema de Bayes , Cromossomos de Mamíferos/genética , Genoma , Alelos , Animais , Peso Corporal , Simulação por Computador , Feminino , Desequilíbrio de Ligação , Masculino , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único , Densidade Demográfica , Locos de Características Quantitativas
15.
J Theor Biol ; 256(2): 276-85, 2009 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-18977361

RESUMO

Phenotypes measured in counts are commonly observed in nature. Statistical methods for mapping quantitative trait loci (QTL) underlying count traits are documented in the literature. The majority of them assume that the count phenotype follows a Poisson distribution with appropriate techniques being applied to handle data dispersion. When a count trait has a genetic basis, "naturally occurring" zero status also reflects the underlying gene effects. Simply ignoring or miss-handling the zero data may lead to wrong QTL inference. In this article, we propose an interval mapping approach for mapping QTL underlying count phenotypes containing many zeros. The effects of QTLs on the zero-inflated count trait are modelled through the zero-inflated generalized Poisson regression mixture model, which can handle the zero inflation and Poisson dispersion in the same distribution. We implement the approach using the EM algorithm with the Newton-Raphson algorithm embedded in the M-step, and provide a genome-wide scan for testing and estimating the QTL effects. The performance of the proposed method is evaluated through extensive simulation studies. Extensions to composite and multiple interval mapping are discussed. The utility of the developed approach is illustrated through a mouse F(2) intercross data set. Significant QTLs are detected to control mouse cholesterol gallstone formation.


Assuntos
Mapeamento Cromossômico/métodos , Modelos Genéticos , Locos de Características Quantitativas , Algoritmos , Animais , Interpretação Estatística de Dados , Distribuição de Poisson
16.
Chin Med J (Engl) ; 120(4): 274-9, 2007 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-17374276

RESUMO

BACKGROUND: Corneal neovascular leakage can lead to edema and secondary scarring. Previous studies have shown that pericytes play a key role in maturation of angiogenesis. The present studies investigate the relationship between vascular permeability and pericyte coverage of endothelial cells in rat corneal neovascular induced by alkali burns. METHODS: Corneal neovascular vessels induced by alkali burns was performed in Sprague-Dawley rats. Corneas were excised on 1, 2, 3, 5, 7 and 10 days after cauterization. The vascular permeability rate was measured by the Evans blue method. The microvessel pericyte coverage index (MPI) was applied to quantify the pericyte coverage through double immunofluorescent staining of frozen sections of corneas with CD31 as the endothelial and alpha-smooth muscle actin (alpha-SMA) as the pericyte markers. The correlation between permeability rate and MPI was analyzed. Pericyte coverage was confirmed ultrastructually using transmission electron microscopy. RESULTS: The vascular permeability rate was (1.14 +/- 0.17), (0.24 +/- 0.08), (0.29 +/- 0.16), (0.14 +/- 0.10), (0.09 +/- 0.06) and (0.05 +/- 0.04) microg x ml(-1) x mm(-2) respectively on 1, 2, 3, 5, 7 and 10 days after cauterization. The MPI was 0, 16.07%, 11.95%, 43.84%, 73.97% and 86.21% respectively at the above mentioned time points. The correlation coefficient between MPI and the permeability rate was -0.943 (P = 0.005). CONCLUSIONS: Pericyte recruitment was significantly correlated with the permeability of corneal neovascularization induced by alkali burns in rats. Therapeutic strategies aiming at anti-leakage should be most effective if they promote pericytes proliferation in the course of corneal neovascularization.


Assuntos
Queimaduras Químicas/fisiopatologia , Permeabilidade Capilar , Neovascularização da Córnea/fisiopatologia , Queimaduras Oculares/fisiopatologia , Pericitos/fisiologia , Álcalis , Animais , Movimento Celular , Córnea/irrigação sanguínea , Córnea/ultraestrutura , Queimaduras Oculares/induzido quimicamente , Feminino , Imunofluorescência , Ratos , Ratos Sprague-Dawley
17.
Cornea ; 25(10 Suppl 1): S36-40, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17001191

RESUMO

PURPOSE: To prepare amniotic extraction (AE) and to test its antiangiogenic effect in vivo and in vitro. METHODS: AE was prepared and diluted to 50, 100, and 200 microg/mL concentrations. Alkali burn-induced corneal neovascularization (NV) was produced and topically treated with different concentrations of AE or 0.1% dexamethasone for 7 days. Normal saline was used as a control. Corneal NV was visualized by heart perfusion of Chinese ink and quantified as the percentage of corneal NV area to the whole corneal area. Human umbilical vein endothelial cells (HUVECs) were primarily cultured. The effects of AE on proliferation and tube formation of HUVECs were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and in vitro angiogenesis assay. Pigment epithelium-derived factor (PEDF) in AE was detected by Western blot. RESULTS: Relative corneal NV area in the control group was 56.6% +/- 9.9%, which was significantly reduced by 50 microg/mL AE (47.6% +/- 6.9%; P = 0.043) and 200 microg/mL AE (34.3% +/- 7.8%; P < 0.001) and by 0.1% dexamethasone (21.1% +/- 1.8%; P < 0.001). HUVEC cell proliferation was significantly decreased after treatment with AE at concentrations of 50 and 100 microg/mL compared with control (P = 0.036 and 0.001, respectively). The tube formation was significantly suppressed by 100 microg/mL AE (70.03% +/- 4.35%) compared with control (100% +/- 4.84%; P = 0.002). No expression of PEDF was detected in AE. CONCLUSION: AE inhibits NV induced by alkali burn. This effect may be elicited at least in part through the inhibiting activity of blood vessel endothelial cells and is not associated with PEDF.


Assuntos
Âmnio/química , Inibidores da Angiogênese/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Neovascularização da Córnea/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Extratos de Tecidos/uso terapêutico , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacologia , Animais , Vasos Sanguíneos/efeitos dos fármacos , Western Blotting , Queimaduras Químicas/tratamento farmacológico , Células Cultivadas , Neovascularização da Córnea/etiologia , Dexametasona/uso terapêutico , Queimaduras Oculares/induzido quimicamente , Proteínas do Olho/metabolismo , Feminino , Humanos , Fatores de Crescimento Neural/metabolismo , Projetos Piloto , Ratos , Ratos Sprague-Dawley , Serpinas/metabolismo , Hidróxido de Sódio , Sais de Tetrazólio , Tiazóis , Extratos de Tecidos/isolamento & purificação , Extratos de Tecidos/farmacologia , Veias Umbilicais/citologia
18.
Invest Ophthalmol Vis Sci ; 46(11): 4062-71, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16249481

RESUMO

PURPOSE: Plasminogen kringle 5 (K5) is a potent angiogenic inhibitor. The purpose of the present study was to evaluate the therapeutic effect of K5 on alkali-burn-induced corneal neovascularization (NV) and to investigate its mechanism of action. METHODS: Corneal NV was induced in rabbits by NaOH. The rabbits received eye drops containing K5 or vehicle alone, four times per day. Corneal NV and inflammation were monitored every other day with a slit lamp microscope, and the length of the vessels in the cornea and the area of NV were measured. Vascular endothelial growth factor (VEGF) was determined by immunohistochemical and Western blot analyses. The TUNEL assay was used to assess the apoptosis of endothelial cells. The effects of K5 on primary bovine aortic endothelial cells (BAECs) were determined by MTT assay, flow cytometry, transmission electron microscopy, and DNA fragmentation assay. RESULTS: Alkali-burn-induced progressive corneal NV and inflammation in the cornea. K5 delayed the onset of corneal NV (P < 0.05) and decreased NV areas (P < 0.05) in a dose-dependent manner. K5 treatment, after the formation of corneal NV, induced regression of newly formatted vessels in the cornea. K5 decreased the inflammatory index in the corneas at different time points after the alkali burn. Corneal VEGF levels were reduced by K5 treatment. K5 inhibits proliferation and induces apoptosis in BAECs. CONCLUSIONS: Topical application of K5 may have therapeutic potential for the chemical burn-induced corneal NV and inflammation. The inhibitory effect of K5 on corneal NV may be by downregulation of VEGF expression.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Queimaduras Químicas/tratamento farmacológico , Neovascularização da Córnea/tratamento farmacológico , Queimaduras Oculares/induzido quimicamente , Fragmentos de Peptídeos/uso terapêutico , Plasminogênio/uso terapêutico , Administração Tópica , Inibidores da Angiogênese/administração & dosagem , Animais , Apoptose , Western Blotting , Queimaduras Químicas/metabolismo , Queimaduras Químicas/patologia , Bovinos , Proliferação de Células , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/ultraestrutura , Queimaduras Oculares/patologia , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Fragmentos de Peptídeos/administração & dosagem , Plasminogênio/administração & dosagem , Coelhos , Hidróxido de Sódio , Fator A de Crescimento do Endotélio Vascular/metabolismo
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