Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 163
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oral Dis ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31901146

RESUMO

OBJECTIVE: The temporomandibular joint (TMJ) displays a high remodelling capability in response to occlusion changes. The purpose of the current study was to investigate the responses of TMJ condyles of growing mice to the installation of a unilateral anterior crossbite (UAC) prosthesis and the replacement of the UAC prothesis with a bilateral anterior elevation (BAE) prosthesis. MATERIALS AND METHODS: C57BL/6J mice were randomly assigned to the blank control and experimental groups. Mice in the experimental groups, UAC was created, while in others, BAE was created after the creation of UAC or removal of UAC. Changes in TMJ condylar cartilage and subchondral bone were assessed. RESULTS: The degradation of condylar cartilage induced by UAC was reversed by BAE, as evaluated by cartilage histochemical changes, collagen II-positive area, collagen X-positive chondrocytes, and expression levels of Adamts-5, Mmp13, Tnf-α and Il-1ß. Subchondral bone was assessed based on the subchondral bone volume, the number of TRAP-positive cells and the Opg/Rankl ratio. CONCLUSION: The growing mouse TMJ condyle displays a high remodelling capability, which can be degenerative or rehabilitative in response to the creation of UAC and the replacement of UAC with BAE. Early correction of occlusion is beneficial for the recovery of degenerative condyles.

2.
Arch Oral Biol ; 109: 104588, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669922

RESUMO

OBJECTIVE: Dental occlusion are frequently changed in clinic. Molecular responses in jaw muscles to aberrant dental occlusion are changes are attractive, yet remain are obscure. DESIGN: Unilateral anterior crossbite (UAC) prostheses were applied to Sprague-Dawley rats and then ceased after two weeks to detect the reactions of the masseter, a representative jaw elevator, and the lateral pterygoid muscle (LPM), a representative jaw depressor. RESULTS: Two weeks of UAC elicited mild injury of the two muscles. Myogenesis and protective reactions were detected as increases in αB-crystallin expression in the masseter after 3 days and in the LPM after 2 weeks, and increases in desmin expression in both muscles after 2 weeks. A switch in fibre types from IIb to IIx occurred in the LPM but not in the masseter. Inflammatory responses, shown by the infiltration of inflammatory cells and increases in TNF-α mRNA expression, and fibrosis responses, shown by increased mRNA expression of Type I and III collagens, appeared very mild in the two muscles. These responses were partially recovered by the cessation of UAC. During the whole process, no obvious changes were observed in mitochondrial function, as indicated by the levels of proliferator-activated receptor γ coactivator 1α, mitofusin-2 and voltage-dependent anion channel. CONCLUSIONS: UAC causes injury and very limited inflammatory and fibrosis adaption in the masseter and LPM. Both muscles respond with myogenesis and protective activity. The LPM responds also with muscle fibre isoform alternations. These alterations were partially recovered by the cessation of dental stimulation at an early stage.


Assuntos
Implantes Dentários/efeitos adversos , Má Oclusão , Músculo Masseter/fisiopatologia , Músculos Pterigoides/fisiopatologia , Animais , Fibrose , Inflamação , Arcada Osseodentária , Músculo Masseter/lesões , Fibras Musculares Esqueléticas , Músculos Pterigoides/lesões , Ratos , Ratos Sprague-Dawley
3.
Int J Mol Sci ; 20(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382618

RESUMO

The temporomandibular joint (TMJ), which is biomechanically related to dental occlusion, is often insulted by osteoarthritis (OA). This study was conducted to clarify the relationship between Indian hedgehog (Ihh) and parathyroid hormone receptor 1 (PTH1R) signaling in modulating the enhanced chondrocyte terminal differentiation in dental stimulated TMJ osteoarthritic cartilage. A gain- and loss-of-function strategy was used in an in vitro model in which fluid flow shear stress (FFSS) was applied, and in an in vivo model in which the unilateral anterior cross-bite (UAC) stimulation was adopted. Ihh and PTH1R signaling was modulated through treating the isolated chondrocytes with inhibitor/activator and via deleting Smoothened (Smo) and/or Pth1r genes in mice with the promoter gene of type 2 collagen (Col2-CreER) in the tamoxifen-inducible pattern. We found that both FFSS and UAC stimulation promoted the deep zone chondrocytes to undergo terminal differentiation, while cells in the superficial zone were robust. We demonstrated that the terminal differentiation process in deep zone chondrocytes promoted by FFSS and UAC was mediated by the enhanced Ihh signaling and declined PTH1R expression. The FFSS-promoted terminal differentiation was suppressed by administration of the Ihh inhibitor or PTH1R activator. The UAC-promoted chondrocytes terminal differentiation and OA-like lesions were rescued in Smo knockout, but were enhanced in Pth1r knockout mice. Importantly, the relieving effect of Smo knockout mice was attenuated when Pth1r knockout was also applied. Our data suggest a chondrocyte protective effect of suppressing Ihh signaling in TMJ OA cartilage which is dependent on PTH1R signaling.

4.
Oral Dis ; 25(7): 1759-1768, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357246

RESUMO

OBJECTIVES: To detect whether early growth response 1 (EGR1) in peripheral blood leucocytes (PBLs) indicates temporomandibular joint (TMJ) osteoarthritis (OA) lesions. MATERIALS AND METHODS: Egr1 mRNA expression levels in PBLs were detected in eight malocclusion patients without temporomandibular disorder (TMD) signs and 16 malocclusion patients with clinical TMD signs with (eight) or without (eight) imaging signs of TMJ OA. Twelve 6-week-old rats were randomized to a control group and a unilateral anterior crossbite (UAC) group and were sampled at 4 weeks. The Egr1 mRNA expression levels in PBLs and protein expression levels in different orofacial tissues were measured. RESULTS: Patients with TMD signs with/without TMJ OA diagnosis showed lower Egr1 mRNA expression levels in PBLs than patients without TMD signs. The lower Egr1 mRNA expression was also found in the PBLs of UAC rats, which were induced to exhibit early histo-morphological signs of TMJ OA lesions. In subchondral bone of UAC rats, EGR1 protein expression was decreased, co-localization of EGR1 with osterix or dentin matrix protein-1 was identified, and the number of EGR1 and osterix double-positive cells was reduced (all p < .05). CONCLUSION: Egr1 reduction in PBLs potentially indicates subchondral bone OA lesions at an early stage.

5.
Arch Toxicol ; 93(6): 1609-1637, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31250071

RESUMO

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity.

6.
Drug Metab Dispos ; 47(8): 854-864, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31076413

RESUMO

The aim of this study was to derive region-specific transporter expression data suitable for in vitro-to-in vivo extrapolation (IVIVE) within a physiologically based pharmacokinetic (PBPK) modeling framework. A meta-analysis was performed whereby literary sources reporting region-specific transporter expression obtained via absolute and relative quantification approaches were considered in healthy adult Caucasian individuals. Furthermore, intestinal total membrane protein yield was calculated to enable mechanistic IVIVE via absolute transporter abundances. Where required, authors were contacted for additional information. A refined database was constructed where samples were excluded based on quantification in, non-Caucasian subjects, disease tissue, subjects <18 years old, duplicated samples, non-total membrane matrix, pooled matrices, or cDNA. Demographic data were collected where available. The weighted and geometric mean, coefficient of variation, and between-study homogeneity was calculated in each of eight gut segments (duodenum, two jejunum, four ileum, and colon) for 16 transporters. Expression data were normalized to that in the proximal jejunum. From a total of 47 articles, the final database consisted of 2238 measurements for 16 transporters. The solute carrier peptide transporter 1 (PepT1) showed the highest jejunal abundance, while multidrug resistance-associated protein (MRP) 2 was the highest abundance ATP-binding cassette transporter. Transporters displaying significant region-specific expression included the ileal bile acid transporter, which showed 18-fold greater terminal ileum expression compared with the proximal jejunum, while MRP3, organic cation transporter type 1 (OCTN1), and OCT1 showed >2-fold higher expression in other regions compared with the proximal jejunum. This is the first systematic analysis incorporating absolute quantification methodology to determine region-specific intestinal transporter expression. It is expected to be beneficial for mechanistic transporter IVIVE in healthy adult Caucasians. SIGNIFICANCE STATEMENT: Given the burgeoning reports of absolute transporter abundances in the human intestine, the incorporation of such information into mechanistic IVIVE-PBPK models could offer a distinct advantage in facilitating the robust assessment of the impact of gut transporters on drug disposition. The systematic and formal assessment via a literature meta-analysis described herein, enables assignment of the regional-specific expression, absolute transporter abundances, interindividual variability, and other associated scaling factors to healthy Caucasian populations within PBPK models. The resulting values are available to incorporate into PBPK models, and offer a verifiable account describing intestinal transporter expression within PBPK models for persons wishing to utilize them. Furthermore, these data facilitate the development of appropriate IVIVE scaling strategies using absolute transporter abundances.

7.
J Oral Rehabil ; 46(9): 820-827, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31046158

RESUMO

Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty-four six-week-old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene-fold changes in PBLs were detected by a microarray analysis comparing rats that received 20-week unilateral anterior crossbite (UAC) treatment with age-matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA-like lesions. The other twenty-four rats were randomly placed in the UAC and control groups at 12- and 20-week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real-time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1-positive, EXPH1-positive and IL10-positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.


Assuntos
Cartilagem Articular , Transtornos da Articulação Temporomandibular , Animais , Côndilo Mandibular , Ratos , Ratos Sprague-Dawley , Articulação Temporomandibular
8.
Opt Lett ; 44(9): 2314-2317, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042212

RESUMO

Integrated lithium niobate (LN) photonic circuits have recently emerged as a promising candidate for advanced photonic functions such as high-speed modulation, nonlinear frequency conversion, and frequency comb generation. For practical applications, optical interfaces that feature low fiber-to-chip coupling losses are essential. So far, the fiber-to-chip loss (commonly >10 dB/facet) has dominated the total insertion losses of typical LN photonic integrated circuits, where on-chip losses can be as low as 0.03-0.1 dB/cm. Here we experimentally demonstrate a low-loss mode size converter for coupling between a standard lensed fiber and sub-micrometer LN rib waveguides. The coupler consists of two inverse tapers that convert the small optical mode of a rib waveguide into a symmetrically guided mode of a LN nanowire, featuring a larger mode area matched to that of a tapered optical fiber. The measured fiber-to-chip coupling loss is lower than 1.7 dB/facet with high fabrication tolerance and repeatability. Our results open the door for practical integrated LN photonic circuits efficiently interfaced with optical fibers.

9.
Oral Dis ; 25(6): 1589-1599, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132303

RESUMO

OBJECTIVE: We aimed to develop a mouse model predominating in a proliferative response in the articular cartilage of the temporomandibular joints. MATERIALS AND METHODS: Bilateral anterior elevation of occlusion was developed by installing metal tubes onto the incisors of mice with edge-to-edge relation to prevent tooth wear, leading to an increase in the vertical height of the dental occlusion with time. Morphological changes and expression changes in Cyclin D1, Aggrecan, and type II and type X collagen in the mandibular condylar cartilage were detected. In addition, cells were isolated from the mandibular condylar cartilage and exposed to cyclic tensile strain (CTS). RESULTS: Compared with age-matched controls, the tooth length was longer at 3 weeks, 7 weeks, and 11 weeks in BAE mice (p < 0.05), with increased condylar cartilage thickness, matrix amount, and cell number (p < 0.05). Compared with the deep zone cells, CTS stimulated the superficial zone cells to express a higher level of proliferating cell nuclear antigen, Cyclin D1, Aggrecan, and type II collagen but a lower level of type X collagen and alkaline phosphatase. CONCLUSION: Bilateral anterior elevation stimulated the proliferative response in the mandibular condylar cartilage, offering a new therapeutic strategy for cartilage degeneration.

10.
Int Immunopharmacol ; 72: 385-394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030094

RESUMO

This study aimed to investigate the interaction between macrophages and fibroblasts in pulmonary fibrosis and the effects of total alkaloids of Stemona tuberosa (STA, 9 alkaloids with relative content of 91.2%) on them. The culture medium of LPS- or IL-4-induced macrophages was used as conditioned medium (CM) to co-culture with fibroblasts to study the effect of macrophages on the differentiation of fibroblasts. Similarly,the CM of TGF-ß1-induced fibroblasts was co-culture with macrophages to study the effect of fibroblasts on the polarization of macrophages. The results showed that the TGF-ß1 level in IL-4-induced (M2) rather than LPS-induced (M1) macrophages was significantly high (p < 0.001), and the SDF-1 level in TGF-ß1-induced fibroblasts (MF) was significantly high (p < 0.001). The expressions of α-SMA and Col-1 in M2-CM-induced fibroblasts and Arg-1 and CXCR4 in MF-CM-induced macrophages were significantly increased (p < 0.01). STA effectively decreased the expressions of α-SMA (p < 0.05, 0.01 at 10, 100 µg/mL), Col-1 (p < 0.05, 0.05, 0.01 at 1, 10, 100 µg/mL), Arg-1 (p < 0.01 at 1, 10, 100 µg/mL) and CXCR4 (p < 0.01, 0.001 at 10, 100 µg/mL), which were consistent with the experimental results in vivo. These results suggested that there was a positive feedback loop between M2 polarization and fibroblast differentiation in pulmonary fibrosis. Further studies showed that the transcription of sdf-1 gene in MF was initiated by JAK2/STAT3 pathway and the M2 polarization was promoted by SDF-1/CXCR4/PI3K/AKT1 pathway. STA blocked the feedback loop by suppressing JAK2/STAT3 pathway in fibroblasts and CXCR4-PI3K/AKT1 pathway in macrophages.

11.
Autophagy ; : 1-18, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31007149

RESUMO

A switch from autophagy to apoptosis is implicated in chondrocytes during the osteoarthritis (OA) progression with currently unknown mechanism(s). In this study we utilized a flow fluid shear stress (FFSS) model in cultured chondrocytes and a unilateral anterior crossbite (UAC) animal model. We found that both FFSS and UAC actively induced endoplasmic reticulum stress (ERS) in the temporomandibular joints (TMJ) chondrocytes, as demonstrated by dramatic increases in expression of HSPA5, p-EIF2AK3, p-ERN1 and ATF6. Interestingly, both FFSS and UAC activated not only pro-death p-EIF2AK3-mediated ERS-apoptosis programs but also pro-survival p-ERN1-mediated autophagic flux in chondrocytes. Data from FFSS demonstrated that MTORC1, a downstream of p-ERN1, suppressed autophagy but promoted p-EIF2AK3 mediated ERS-apoptosis. Data from UAC model demonstrated that at early stage both the p-ERN1 and p-EIF2AK3 were activated and MTORC1 was inhibited in TMJ chondrocytes. At late stage, MTORC1-p-EIF2AK3-mediated ERS apoptosis were predominant, while p-ERN1 and autophagic flux were inhibited. Inhibition of MTORC1 by TMJ local injection of rapamycin in rats or inducible ablation of MTORC1 expression selectively in chondrocytes in mice promoted chondrocyte autophagy and suppressed apoptosis, and reduced TMJ cartilage loss induced by UAC. In contrast, MTORC1 activation by TMJ local administration of MHY1485 or genetic deletion of Tsc1, an upstream MTORC1 suppressor, resulted in opposite effects. Collectively, our results establish that aberrant mechanical loading causes cartilage degeneration by activating, at least in part, the MTORC1 signaling which modulates the autophagy and apoptosis programs in TMJ chondrocytes. Thus, inhibition of MTORC1 provides a novel therapeutic strategy for prevention and treatment of OA. Abbreviations : ACTB: actin beta; ATF6: activating transcription factor 6; BECN1: beclin 1; BFL: bafilomycin A1; CASP12: caspase 12; CASP3: caspase 3; DAPI: 4',6-diamidino-2-phenylindole; DDIT3: DNA-damage inducible transcript 3; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERS: endoplasmic reticulum stress; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; FFSS: flow fluid shear stress; HSPA5/GRP78/BiP: heat shock protein 5; LAMP2: lysosome-associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; OA: osteoarthritis; PRKAA1/2/AMPK1/2: protein kinase, AMP-activated, alpha 1/2 catalytic subunit; RPS6: ribosomal protein S6; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TG: thapsigargin; TMJ: temporomandibular joints; TSC1/2: tuberous sclerosis complex 1/2; UAC: unilateral anterior crossbite; UPR: unfolded protein response; XBP1: x-box binding protein 1.

12.
Nature ; 568(7752): 373-377, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30858615

RESUMO

Optical frequency combs consist of equally spaced discrete optical frequency components and are essential tools for optical communication, precision metrology, timing and spectroscopy1-9. At present, combs with wide spectra are usually generated by mode-locked lasers10 or dispersion-engineered resonators with third-order Kerr nonlinearity11. An alternative method of comb production uses electro-optic (EO) phase modulation in a resonator with strong second-order nonlinearity, resulting in combs with excellent stability and controllability12-14. Previous EO combs, however, have been limited to narrow widths by a weak EO interaction strength and a lack of dispersion engineering in free-space systems. Here we overcome these limitations by realizing an integrated EO comb generator in a thin-film lithium niobate photonic platform that features a large EO response, ultralow optical loss and highly co-localized microwave and optical fields15, while enabling dispersion engineering. Our measured EO comb spans more frequencies than the entire telecommunications L-band (over 900 comb lines spaced about 10 gigahertz apart), and we show that future dispersion engineering can enable octave-spanning combs. Furthermore, we demonstrate the high tolerance of our comb generator to modulation frequency detuning, with frequency spacing finely controllable over seven orders of magnitude (10 hertz to 100 megahertz), and we use this feature to generate dual-frequency combs in a single resonator. Our results show that integrated EO comb generators are capable of generating wide and stable comb spectra. Their excellent reconfigurability is a powerful complement to integrated Kerr combs, enabling applications ranging from spectroscopy16 to optical communications8.

13.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893870

RESUMO

Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1ß and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1⁻10 µM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1ß and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 µM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/complicações , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Concanavalina A/toxicidade , Glicosídeos/química , Glicosídeos/uso terapêutico , Vincetoxicum/química , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos
14.
Mol Plant Pathol ; 20(6): 843-856, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30912612

RESUMO

Valsa mali is the causal agent of apple Valsa canker, a destructive disease in East Asia. Effector proteins play important roles in the virulence of phytopathogenic fungi, and we identified five Hce2 domain-containing effectors (VmHEP1, VmHEP2, VmHEP3, VmHEP4 and VmHEP5) from the V. mali genome. Amongst these, VmHEP1 and VmHEP2 were found to be up-regulated during the early infection stage and VmHEP1 was also identified as a cell death inducer through its transient expression in Nicotiana benthamiana. Although the deletion of each single VmHEP gene did not lead to a reduction in virulence, the double-deletion of VmHEP1 and VmHEP2 notably attenuated V. mali virulence in both apple twigs and leaves. An evolutionary analysis revealed that VmHEP1 and VmHEP2 are two paralogues, under purifying selection. VmHEP1 and VmHEP2 are located next to each other on chromosome 11 as tandem genes with only a 604 bp physical distance. Interestingly, the deletion of VmHEP1 promoted the expression of VmHEP2 and, vice versa, the deletion of VmHEP2 promoted the expression of VmHEP1. The present results provide insights into the functions of Hce2 domain-containing effectors acting as virulence factors of V. mali, and provide a new perspective regarding the contribution of tandem genes to the virulence of phytopathogenic fungi.

15.
Nat Commun ; 10(1): 978, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816151

RESUMO

Microresonator Kerr frequency combs could provide miniaturised solutions for a wide range of applications. Many of these applications however require further manipulation of the generated frequency comb signal using photonic elements with strong second-order nonlinearity (χ(2)). To date these functionalities have largely been implemented as discrete components due to material limitations, which comes at the expense of extra system complexity and increased optical losses. Here we demonstrate the generation, filtering and electro-optic modulation of a frequency comb on a single monolithic integrated chip, using a nanophotonic lithium-niobate platform that simultaneously possesses large electro-optic (χ(2)) and Kerr (χ(3)) nonlinearities, and low optical losses. We generate broadband Kerr frequency combs using a dispersion-engineered high-Q lithium-niobate microresonator, select a single comb line using an electrically programmable add-drop filter, and modulate the intensity of the selected line. Our results pave the way towards monolithic integrated frequency comb solutions for spectroscopy, data communication, ranging and quantum photonics.

16.
Sci Total Environ ; 668: 271-282, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-30852204

RESUMO

The Beijing-Tianjin-Hebei region's rapid economic development has led to a dramatic increase in its CO2 emissions, which is closely related to various regions' consumption habits and structures. In this paper, the decomposition analysis method based on input and output (IO-SDA) was applied to decompose the CO2 emissions change of the Beijing-Tianjin-Hebei region from 1997 to 2012 into five driving factors: population, carbon emission efficiency, production structure, final use structure and per capita regional GDP, and then the final use structure factor was further analyzed. The results show that: (1) the population and per capita regional GDP promote the CO2 emissions of all regions; Carbon emission efficiency is the biggest offsetting factor; The effect of final use structure changes on the growth of CO2 emissions in Beijing and Hebei remains unchanged. The effect on Tianjin was from 0.7Mt offset to 0.8Mt promotion. (2) Urban household consumption is the most important factor offsetting CO2 emissions in Beijing. Investment and export are the most important final use types for promoting the growth of CO2 emissions in Tianjin and Hebei, with the contribution of 95.78% and 88.09%, respectively. (3) From the sectoral perspective: The construction sector has the greatest impact on the total capital formation of the three regions. In terms of exports, Beijing's tertiary industry has the largest offsetting effect, while Tianjin and Hebei mainly rely on the promotion of metal smelting and other manufacturing industries. Finally, some policy implications for low carbonization are proposed in the Beijing-Tianjin-Hebei region.

17.
Int J Mol Sci ; 20(3)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759829

RESUMO

Tibetan wild barley has been identified to show large genetic variation and stress tolerance. A genome-wide association (GWA) analysis was performed to detect quantitative trait loci (QTLs) for drought tolerance using 777 Diversity Array Technology (DArT) markers and morphological and physiological traits of 166 Tibetan wild barley accessions in both hydroponic and pot experiments. Large genotypic variation for these traits was found; and population structure and kinship analysis identified three subpopulations among these barley genotypes. The average LD (linkage disequilibrium) decay distance was 5.16 cM, with the minimum on 6H (0.03 cM) and the maximum on 4H (23.48 cM). A total of 91 DArT markers were identified to be associated with drought tolerance-related traits, with 33, 26, 16, 1, 3, and 12 associations for morphological traits, H⁺K⁺-ATPase activity, antioxidant enzyme activities, malondialdehyde (MDA) content, soluble protein content, and potassium concentration, respectively. Furthermore, 7 and 24 putative candidate genes were identified based on the reference Meta-QTL map and by searching the Barleymap. The present study implicated that Tibetan annual wild barley from Qinghai⁻Tibet Plateau is rich in genetic variation for drought stress. The QTLs detected by genome-wide association analysis could be used in marker-assisting breeding for drought-tolerant barley genotypes and provide useful information for discovery and functional analysis of key genes in the future.


Assuntos
Hordeum/genética , Locos de Características Quantitativas/genética , Estresse Fisiológico/genética , Adaptação Fisiológica/genética , Biomarcadores/metabolismo , Secas , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Desequilíbrio de Ligação/genética , Fenótipo , Melhoramento Vegetal/métodos , Tibet
18.
Nature ; 566(7742): 89-93, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30664747

RESUMO

The field of miniature mechanical oscillators is rapidly evolving, with emerging applications including signal processing, biological detection1 and fundamental tests of quantum mechanics2. As the dimensions of a mechanical oscillator shrink to the molecular scale, such as in a carbon nanotube resonator3-7, their vibrations become increasingly coupled and strongly interacting8,9 until even weak thermal fluctuations could make the oscillator nonlinear10-13. The mechanics at this scale possesses rich dynamics, unexplored because an efficient way of detecting the motion in real time is lacking. Here we directly measure the thermal vibrations of a carbon nanotube in real time using a high-finesse micrometre-scale silicon nitride optical cavity as a sensitive photonic microscope. With the high displacement sensitivity of 700 fm Hz-1/2 and the fine time resolution of this technique, we were able to discover a realm of dynamics undetected by previous time-averaged measurements and a room-temperature coherence that is nearly three orders of magnitude longer than previously reported. We find that the discrepancy in the coherence stems from long-time non-equilibrium dynamics, analogous to the Fermi-Pasta-Ulam-Tsingou recurrence seen in nonlinear systems14. Our data unveil the emergence of a weakly chaotic mechanical breather15, in which vibrational energy is recurrently shared among several resonance modes-dynamics that we are able to reproduce using a simple numerical model. These experiments open up the study of nonlinear mechanical systems in the Brownian limit (that is, when a system is driven solely by thermal fluctuations) and present an integrated, sensitive, high-bandwidth nanophotonic interface for carbon nanotube resonators.

19.
Arch Oral Biol ; 98: 17-25, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30419485

RESUMO

OBJECTIVE: To investigate the changes in insulin-like growth factor-1 (IGF-1) expression levels in the degenerative mandibular condylar cartilage. DESIGN: Thirty-six rats were divided into the unilateral anterior crossbite and control groups. The expression levels of IGF-1; IGF-1 receptor (IGF-1R); IGF-binding protein-3 and -5 (IGFBP-3 and -5); proliferating cell nuclear antigen (PCNA); aggrecan; type-I, -II, -VI, and -X collagen; tissue inhibitor of metalloproteinases-1 and -3 (TIMP-1 and -3); metalloproteinases of matrix metalloproteinases-3 and-13 (MMP-3 and -13); a disintegrin and metalloproteinase thrombospondin-4 and -5 (ADAMTS-4 and -5); alkaline phosphatase (ALP); ß-glucuronidase; and N-acetyl-ß-glucosaminidase in the mandibular condylar cartilage were assessed. RESULTS: The protein expression levels of IGF-1and IGF-1R were increased from week 4 in the unilateral anterior crossbite group. The mRNA expression level of IGFBP-3 and -5 was upregulated from week 4 and week 2, respectively; that of IGFBP-3 was downregulated at week 8; and that of PCNA, type-II collagen, type-X collagen, aggrecan, TIMP-1, and TIMP-3 was downregulated, whereas that of MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, ß-glucuronidase, and N-acetyl-ß-glucosaminidase were upregulated from week 2. The positive area size of type-I collagen was increased and that of type VI collagen was decreased from week 2. The positive area size of type X collagen was increased at week 2 but decreased at week 8. The percentage of ALP-positive cells was increased from week 4. CONCLUSIONS: Unilateral anterior crossbite stimulated the multifarious expression of IGF-1 and IGFBP, which may be linked to chondrocyte proliferation and differentiation in the mandibular condylar cartilage that showed progressive degeneration.


Assuntos
Doenças das Cartilagens/etiologia , Cartilagem Articular/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Má Oclusão/complicações , Côndilo Mandibular/metabolismo , Côndilo Mandibular/patologia , Transtornos da Articulação Temporomandibular/etiologia , Proteína ADAMTS4/metabolismo , Proteína ADAMTS5/metabolismo , Agrecanas/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Condrócitos/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Glucuronidase/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor IGF Tipo 1/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Regulação para Cima
20.
J Oral Rehabil ; 46(4): 340-348, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30556174

RESUMO

BACKGROUND: The temporomandibular joint (TMJ) disc plays a role in joint movement and in load absorbance and distribution. An experimental unilateral anterior crossbite (UAC) prosthesis induces mandibular condylar cartilage degeneration in rats. However, the changes in the articular disc are still unknown. OBJECTIVE: To describe changes in the TMJ discs of UAC rats. METHODS: The discs of fifty-four Sprague-Dawley rats, equally distributed into a UAC group and an age-matched sham-operated control group at 4, 12 and 20 weeks (n = 9), were evaluated by gross and histomorphological observation and by detection at the mRNA or protein expression levels of the markers related to the matrix elements. RESULTS: No macro- or micro-morphological differences were observed between groups. However, there were catabolic degradative changes at the molecular level in the UAC group, showing a significant reduction in the mRNA and/or protein expression levels of many molecules. The reduction became worse with time (P < 0.05). The reduced molecules included: (a) those related to the extracellular matrix, such as type I collagen, decorin and fibromodulin; (b) those related to chondrogenesis, such as type II collagen and aggrecan; and (c) those related to osteogenesis, such as alkaline phosphatase and runt-related transcription factor 2. The mRNA expression of vascular endothelial growth factor did not change. In contrast, fibronectin, which can promote wound healing, and its N-terminal fragment, which can induce cartilage degradation, were accumulated (P < 0.05). CONCLUSION: TMJ discs were stimulated to catabolic changes by the aberrant dental occlusion and seemed to go to inanimate with time.


Assuntos
Má Oclusão/metabolismo , Má Oclusão/patologia , Côndilo Mandibular/metabolismo , Côndilo Mandibular/patologia , Disco da Articulação Temporomandibular/metabolismo , Disco da Articulação Temporomandibular/patologia , Animais , Cartilagem Articular/patologia , Condrócitos/patologia , Oclusão Dentária , Modelos Animais de Doenças , Feminino , Má Oclusão/complicações , Fenômenos Mecânicos , Ratos , Ratos Sprague-Dawley
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA