Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 659
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-32227303

RESUMO

Litter decomposition is of utmost importance to elemental cycling in terrestrial ecosystems, with litter quality being frequently considered to predominantly control litter decomposition. However, how acid rain (AR) would affect litter decomposition and its elements release remains inconclusive, although AR has widely occurred in Europe, North America, and East Asia. This study was conducted to observe leaf litter decomposition and release of carbon (C), nitrogen (N), and phosphorus (P) of three crops (maize, rice, and soybean) under simulated AR treatments. Results showed that the accumulated mass loss during decomposition was significantly different among species, supporting the view of litter quality predominantly controlling decomposition. Specifically, quality dependence of litter decomposition was observed in the late stage of decomposition, while mass loss of litters was comparable in the first month among species. With decomposition, the litter C/N ratio significantly increased for the three species while the C/P and N/P ratios significantly decreased or tended to decrease, suggesting that litter N was released preferentially over C and P. However, AR treatments did not significantly affect litter decomposition and its elements release in our investigation period. Moreover, litter P content appeared to strongly affect the release of C, N, and P during litter decomposition, and such P dependence could to some extent be alleviated by AR treatments. Our results suggest that AR may change the quality dependence of litter decomposition and further studies are needed to illustrate its potential mechanisms.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32142415

RESUMO

OBJECTIVE: In most binocular stereo vision aided system, stereo matching algorithm is the core content. In our research, we found that in existing models, the pure computational models lack biological basis, difficult to combination with bioengineering, and is too complex to hardware design. At the same time, the existing biological models have some deficiencies in accuracy. Therefore, we design a biology-based binocular image matching method to improve the compatibility and accuracy of the auxiliary system. METHODS: We simulate some functions and structures of V1 and V2 layers network according to the discoveries of modern neurobiology. The receptive fields of V1 layer cells are aggregated in a certain way to obtain the receptive fields of V2 layer, and the primary disparity is obtained in V2 layer. The model emphasizes the biological structure, low in hardware complexity, high in replicability, and the accuracy is improved. The basic unit of the model is the receptive field of simple cells rather than the pixels, so the whole model is based on the receptive field of visual cells, which has great biological significance. CONCLUSION: This method can get a better result than other visual nerve models, and has a higher replicability than non-biological models. SIGNIFICANCE: because of the compatibility and accuracy of this method, the model can guide the design of visual aided model.

3.
J Econ Entomol ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173761

RESUMO

The diamondback moth, Plutella xylostella (L.), is a worldwide insect pest of cruciferous crops. Although insecticides have long been used for its control, diamondback moth rapidly evolves resistance to almost any insecticide. In insects, juvenile hormone (JH) is critically involved in almost all biological processes. The correct activity of JH depends on the precise regulation of its titer, and juvenile hormone esterase (JHE) is the key regulator. Thus, JH and JHE have become important targets for new insecticide development. Trifluoromethyl ketones are specific JHE inhibitors, among which 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP) has the highest activity. The interaction effects between pretreatment with or combination of OTFP and the insecticides diafenthiuron, indoxacarb, and Bacillus thuringiensis (Bt) were investigated in diamondback moth larvae to determine OTFP's potential as an insecticide synergist. In third-instar larvae, both pretreatment and combination treatment with OTFP decreased or antagonized the toxicities of diafenthiuron, indoxacarb, and Bt at all set concentrations. In fourth-instar larvae, combination treatment with OTFP decreased or antagonized the toxicities of diafenthiuron and indoxacarb at all set concentrations. However, it increased or synergized the toxicity of Bt at lower concentrations despite the limited effect at higher concentrations. Our results indicated that the effect of OTFP on the toxicities of insecticides varied with the type and concentration, larval stage, and treatment method. These findings contribute to the better use of OTFP in diamondback moth control.

5.
Curr Med Sci ; 40(1): 1-8, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32166659

RESUMO

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes. As a confirmed tumor suppressor, PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells. In the brains of Alzheimer's disease (AD) patients, decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and Aß generation. In this review, we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD. The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed. It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.

6.
Int J Rheum Dis ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32189478

RESUMO

AIM: Previous studies have discussed association of FcγRIIA-R/H131 polymorphism and systemic lupus erythematosus (SLE), lupus nephritis (LN) risk. However, conclusions were inconsistent. METHODS: A meta-analysis was performed in this study with allelic contrast (allele R vs H), additive model (genotype RR vs HH), recessive model (genotype RR vs RH + HH), and dominant model (genotype RR + RH vs HH). RESULTS: A total of 33 studies discussed the correlation between FcγRIIA-R/H131 polymorphism and SLE, involving 5652 SLE patients and 6322 controls. Allele R was significantly related to SLE in the overall population (odds ratio [OR] = 1.238, P < .001), Asian (OR = 1.237, P < .001) and European population (OR = 1.212, P = .012). Additive, recessive and dominant models were correlating with SLE in the overall population (OR = 1.448, P < .001; OR = 1.303, P < .001; OR = 1.310, P < .001), Asian population (OR = 1.640, P = .001; OR = 1.437, P < .001; OR = 1.344, P = .005), respectively. In addition, 22 studies evaluated relation of FcγRIIA-R/H131 polymorphism with LN, involving 2065 patients with LN, and 2023 patients without LN. Results showed that allele R and the other 3 models related to LN susceptibility in the overall population when discussing differences of polymorphism between patients with/without LN. We further compared differences of polymorphism between patients with LN and controls, showing that additive and recessive models related to LN risk in the overall population, Asian, European and North American populations. CONCLUSION: In summary, FcγRIIA-R/H131 polymorphism is associated with SLE and LN.

7.
HLA ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107885

RESUMO

HLA-C*07:02:83 differs from HLA-C*07:02:01:01 (387C- > A, P105P).

8.
Mol Med Rep ; 21(3): 1590-1596, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016461

RESUMO

Increasing research has demonstrated that expression of brain and muscle ARNT­like 1 (BMAL1) and other circadian clock genes can be regulated by drugs and toxicants. We previously demonstrated that icariin, extracted from Herba Epimedii, sromotes osteogenic differentiation. However, the mechanism underlying the association between icariin and BMAL1 in osteogenic differentiation of bone marrow­derived mesenchymal stem cells (BMSCs) remains unclear. The present study was designed with an aim to clarify the association between icariin and BMAL1 in osteogenic differentiation of BMSCs. The Cell Counting Kit­8 assay was used to evaluate cell proliferation. The expression of bone morphogenetic protein 2 (BMP2), RUNX family transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OC) and BMAL1 in BMSCs was evaluated by reverse transcription­quantitative PCR and western blotting. ALP and Alizarin red S (ARS) staining were also performed. Icariin promoted BMSC proliferation, and upregulated expression of osteogenic genes and BMAL1. In addition, expression of the osteogenic genes BMP2, RUNX2, ALP and OC were upregulated by BMAL1 overexpression. Furthermore, we confirmed that BMAL1 deficiency suppressed osteogenic differentiation in BMSCs. Finally, ARS staining of BMAL1­/­ BMSCs revealed that BMAL1 was an essential intermediary in matrix mineralization during osteogenic differentiation. In conclusion, these results demonstrated that icariin promoted osteogenic differentiation through BMAL1­BMP2 signaling in BMSCs. The present study thus described a novel target of icariin that has potential applications in the treatment of osteogenic disorders.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 1-6, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027244

RESUMO

OBJECTIVE: To investigate the efficacy and safety of arsenic trioxide combined with ATRA and chemo- therapy for treatment of relapsed acute promyelocytic leukemia (APL) patients. METHODS: The clinic data of 25 patients with relapse APL treated in our hospital from 1996 to 2013 were collected and analyzed. Among the 25 patients, 15 patients suffered first-time hematological relapse (HR), and the other 10 patients showed first-time molecular relapse (MR). The patients with first-time replase were treated with ATO+ATRA+Anthracycline re-induction chemotherapy. The clinical features, complete remission (CR) rate, overall survival (OS), disease-free survival (DFS) and adverse events after re-induction therapy were analyzed. RESULTS: Fourteen of 15 hematological relapsed patients achieved the second-time hematological complete remission (CR2) after re-induction therapy except one patient died of bleeding complication during the re-induction. 8 of 14 patient showed molecular complete remission (CRm) after two cycles of therapy with this regimen. Totally, eleven out of the 14 HR patients were alive without disease till the last follow-up, and 3 of the 14 HR patients died because of bleeding complications. All of the 10 molecular relapsed patients received the second CRm after treated by the regimen. Among these 10 patients, 6 patients suffered only once relapse and continued with the molecular CR2 status, and for the other 4 patients with more than two-relapses, only 1 survived untill 89.3 months after achieved second-time CRm, and other 3 patients died because of bleeding complications. CONCLUSION: For relapsed APL patients, the treatment with ATO+ATRA+chemotherapy regimen after relapse still shows encouraging efficacy, no matter whether or not the application of ATO in the previous regimens. In addition, patients with more than two molecular relapses show a poor prognosis.


Assuntos
Arsenicais , Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos , Indução de Remissão , Resultado do Tratamento , Tretinoína
10.
Sci Rep ; 10(1): 2604, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054869

RESUMO

Although postoperative cholangioscopy (POC) guided electrohydraulic lithotripsy (EHL) is considered to be a conventional technique for residual biliary calculi, its efficacy still needs to be improved to fit in the managemet of refractory calculi. This study evaluated the efficacy and safety of combined lithotripsy of mechanical clamping and electrohydraulics in fragmentation and removal of refractory calculi. Totally, 281 patients, who suffered from residual biliary calculi after hepatectomy and underwnet POC from August 2016 to June 2018 were involved. The first 128 patients were subjected to conventional EHL, and later consective 153 to combined lithotripsyof mechanical clamping and EHL. Perioperative data, technical information, treatment outcomes and follow-up results were collected. Clinical characteristics were statistically comparable (P > 0.05). The overall POC interventional sessions (2.0 ± 0.65 vs. 2.9 ± 1.21 sessions), average operating time (99.1 ± 34.88 vs. 128.6 ± 72.87 minutes), incidence of intraoperative hemobilia (4.58% vs. 10.93%), cholangitis (6.54% vs. 14.06%), postoperative complications (10.45% vs. 21.87%), T-tube retaining time after first POC (20.7 ± 5.35 vs. 28.1 ± 8.28 days), and treatment costs ($2375 ± 661.72 vs. $3456.7 ± 638.07) were significantly lower in the combined lithotripsy group than those in the EHL group (P < 0.05). There were no differences between the two groups in calculi recurrence at half-a year, or one year follow-up. In conclusion, combined lithotripsy of mechanical clamping and electrohydraulics can safely and effectively benefit postoperative patients along with refractory residual biliary calculi.

12.
Neurotherapeutics ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32096091

RESUMO

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease for which there are limited therapeutic strategies. Protein phosphatase 2A (PP2A) activity is decreased in AD brains, which promotes the hyperphosphorylation of Tau and APP, thus participate in the formation of neurofibrillary tangles (NFTs) and ß-amyloid (Aß) overproduction. In this study, the effect of synthetic tricyclic sulfonamide PP2A activators (aka SMAPs) on reducing AD-like pathogenesis was evaluated in AD cell models and AD-like hyperhomocysteinemia (HHcy) rat models. SMAPs effectively increased PP2A activity, and decreased tau phosphorylation and Aß40/42 levels in AD cell models. In HHcy-AD rat models, cognitive impairments induced by HHcy were rescued by SMAP administration. HHcy-induced tau hyperphosphorylation and Aß overproduction were ameliorated through increasing PP2A activity on compound treatment. Importantly, SMAP therapy also prevented neuronal cell spine loss and neuronal synapse impairment in the hippocampus of HHcy-AD rats. In summary, our data reveal that pharmacological PP2A reactivation may be a novel therapeutic strategy for AD treatment, and that the tricyclic sulfonamides constitute a novel candidate class of AD therapeutic.

13.
Structure ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32027819

RESUMO

Metazoan retromer (VPS26/VPS35/VPS29) associates with sorting nexins on endosomal tubules to sort proteins to the trans-Golgi network or plasma membrane. Mechanisms of metazoan retromer assembly remain undefined. We combine single-particle cryoelectron microscopy with biophysical methods to uncover multiple oligomer structures. 2D class averages reveal mammalian heterotrimers; dimers of trimers; tetramers of trimers; and flat chains. These species are further supported by biophysical solution studies. We provide reconstructions of all species, including key sub-structures (∼5 Å resolution). Local resolution variation suggests that heterotrimers and dimers adopt multiple conformations. Our structures identify a flexible, highly conserved electrostatic dimeric interface formed by VPS35 subunits. We generate structure-based mutants to disrupt this interface in vitro. Equivalent mutations in yeast demonstrate a mild cargo-sorting defect. Our data suggest the metazoan retromer is an adaptable and plastic scaffold that accommodates interactions with different sorting nexins to sort multiple cargoes from endosomes their final destinations.

14.
Clin Cancer Res ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029439

RESUMO

PURPOSE: Cytarabine, 100-200 mg/mE+2/d, is commonly-used in induction therapy of acute myeloid leukaemia (AML). Whether a higher dose of cytarabine would be more effective is unknown. Also, there is controversy whether high-dose cytarabine is better than an intermediate-dose combined with other drugs for post-remission therapy. In this open-label, randomized, parallel controlled group study, roles of intermediate-dose cytarabine were investigated. SUBJECTS AND METHODS: Subjects with AML age 15-55 years were randomized to receive daunorubicin, omacetaxine mepesuccinate and conventional- or intermediate-dose cytarabine. Subjects achieving complete remission were randomized to receive 3 courses of high-dose cytarabine or 2 courses of intermediate-dose cytarabine with daunorubicin in the 1st and mitoxantrone in the 2nd course. The primary endpoint was disease-free survival (DFS). RESULTS: 591 subjects were randomized to intermediate- (N=295) or conventional-dose (N=296) cytarabine group. Three-year DFSs were 67% (95% confidence interval [CI], 61-73) in the intermediate-dose cohort compared with 54% (95%CI, 48-61) in the conventional-dose cohort (Hazard Ratio [HR]=0.67; 95%CI, 0.51-0.89; P=0.005). Three-year survivals were 68% (95%CI, 63-74) and 59% (95%CI, 53-65; HR=0.720 95%CI, 0.56-0.94; P=0.014). Two course of intermediate-dose cytarabine with daunorubicin or mitoxantrone resulted in similar DFS and survival as three course of high-dose cytarabine when used for post-remission therapy. CONCLUSIONS: Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML age 15-55 years compared with conventional-dose cytarabine.

15.
Plant Sci ; 292: 110379, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32005384

RESUMO

Plant defensins have been implicated in the plant defense system, but their role in poplar immunity is still unclear. In the present study, we present evidence that PtDefensin, a putative plant defensin, participates in the defense of poplar plants against Septotis populiperda infection. After the construction of recombinant plasmid PET-32a-PtDefensin, PtDefensin protein was expressed in Escherichia coli strain BL21 (DE3) and purified through Ni-IDA resin affinity chromatography. The Trx-PtDefensin fusion protein displayed no cytotoxic activity against RAW264.7 cells but had cytotoxic activity against E. coli K12D31 cells. Analyses of PtDefensin transcript abundance showed that the expression levels of PtDefensin responded to abiotic and biotic stresses. Overexpression of PtDefensin in 'Nanlin 895' poplars (Populus × euramericana cv 'Nanlin895') increased resistance to Septotis populiperda, coupled with upregulation of MYC2 (basic helix-loop-helix (bHLH) transcription factor) related to jasmonic acid (JA) signal transduction pathways and downregulation of Jasmonate-zim domain (JAZ), an inhibitor in the JA signal transduction pathway. We speculate that systemic acquired resistance (SAR) was activated in non-transgenic poplars after S. populiperda incubation, and that induced systemic resistance (ISR) was activated more obviously in transgenic poplars after S. populiperda incubation. Hence, overexpression of PtDefensin may improve the resistance of poplar plants to pathogens.

16.
Medicine (Baltimore) ; 99(8): e19189, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080102

RESUMO

Studies on the relationship between ABCB1 3435C>T polymorphism (rs1045642) and colorectal cancer (CRC)susceptibility have yielded inconclusive results. To clarify this issue, we undertook a meta-analysis to investigate the relationship between rs1045642 and CRC risk.Three electronic scientific publication databases (Cochrane Library, Pubmed, Embase) were screened using specific search terms. Relevant literature was identified using literature traceability methods. Selected publications were evaluated according to the inclusion and exclusion criteria. Effect size information (odds ratio and the corresponding 95% confidence interval [CI]) was obtained following quality assessment and data extraction from the included publications, and a meta-analysis conducted. Statistical analysis was performed with the Stata sofz (Version 13.0) software.Overall, 17 case-control studies involving 7129 CRC patients and 7710 healthy control subjects satisfied the criteria for inclusion in the meta-analysis. There was no significant association between ABCB1 3435C>T polymorphism and CRC risk in any of the genetic models. In the CC versus CT model (I = 20.9%, Pheterogeneity = .276), CC versus CT + TT model (I = 45.6%, Pheterogeneity = .102) and CT versus CC + TT model (I = 17.8%, Pheterogeneity = .298) analyses, between-study heterogeneities were detected as significant in Asian populations. In the CT versus TT model (I = 24%, Pheterogeneity = .254) and CC + CT versus TT model (I = 0, Pheterogeneity = .55), between-study heterogeneities were found to be significant in groups of different populations.The meta-analysis described here suggests that the ABCB1 3435C>T polymorphism is not related to CRC susceptibility.


Assuntos
Neoplasias Colorretais/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
17.
Sci Total Environ ; 713: 136600, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31958726

RESUMO

Acid rain has been one of the major environmental problems in industrial countries. While it may affect the litter decomposition, a highly important microbial-driven biogeochemical process, knowledge about the impact of acid rain on litter-decomposing microbial communities and their functions remains unclear. Therefore, this experiment was conducted to investigate how acid rain treatments would alter microbial communities and their functions during litter decomposition of three major commodity crops (maize, rice, and soybean) for six months from June to December 2018. We used litterbag method to determine litter decomposition,while the phospholipid fatty acid (PLFA) and fluorometric methods were used to reveal changes in the litter-adhering microbial community parameters and activities of enzymes involved in the litter decomposition and nutrient release (including carbon [C], nitrogen [N], and phosphorus [P]), respectively. Our results showed that microbial community composition and functions were significantly different among litter types, but not significantly altered by acid rain treatments during the experimental period. The enzyme activities significantly correlated with each other, thus suggesting that microbial requirements for C, N, and P were coupled together during litter decomposition. Moreover, the enzyme activities, at large, did not correlate to microbial community composition, thus indicating the asymmetric relationship between microbial community structure and functions. Our results imply that crop litter type and substrate availability determined the microbial community composition and functions, while litter-inhabiting microbial communities demonstrated substantial resilience under acid rain pressure throughout the experimental period. These results also predict that litter (crop residues) decomposition may not be altered by acid rains in the subtropical agroecosystem, due to relatively high resilience of litter-decomposing microbial communities.


Assuntos
Chuva Ácida , Microbiota , Florestas , Nitrogênio , Folhas de Planta , Solo , Microbiologia do Solo
18.
J Magn Reson Imaging ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31975534

RESUMO

BACKGROUND: Right ventricular dilation and dysfunction is a common long-term complication in patients with repaired pulmonary stenosis (rPS). Additionally, abnormal right and left ventricular interactions have been reported in right-sided heart defect after intervention, including in pulmonary stenosis. PURPOSE: To analyze ventricular strain, remodeling, and left and right ventricular interactions in rPS patients with preserved right ventricular ejection fraction (RVEF) compared with healthy children using cardiac magnetic resonance. STUDY TYPE: A cross-sectional study. POPULATION: In all, 34 rPS patients and 10 healthy children volunteers (controls). FIELD STRENGTH/SEQUENCE: 3.0T/2D balanced steady-state free precession (2D b-SSFP) cine, late gadolinium enhancement (LGE), and 2D phase contrast (2D-PC). ASSESSMENT: Pulmonary regurgitation (PR) fractions of the main pulmonary artery, biventricular volumes, masses, function, and cardiac strain. STATISTICAL TESTS: Mann-Whitney U-test, t-test, Pearson correlation coefficients, Spearman's correlation coefficients, and intraclass correlation coefficients analysis were performed. RESULTS: For group analysis, the right ventricular (RV) global circumferential strain and radial strain were significantly increased in patients when compared with controls (-13.57 ± 2.69 vs. -5.91 ± 3.16, P < 0.001; 25.31 ± 8.12 vs. 9.87 ± 5.32, P < 0.001, respectively). The fraction of PR displayed moderate correlation with right ventricular end-diastolic volume index (RVEDVi) (r = 0.452, P = 0.022). RVEDVi and mass index were larger in patients vs. control (104.92 ± 27.46 vs. 85.15 ± 11.98, P = 0.016; 18.28 ± 4.95g/m2 vs. 11.67 ± 2.14 g/m2 , P < 0.001, respectively). Patients presented with preserved left ventricular ejection function, but was lower than healthy controls (60.89% ± 4.89% vs. 65.95% ± 4.56%, P = 0.006). Regional circumferential strain of segment 3 of left ventricle (LV) were significantly decreased in patients (-7.79 ± 6.52 vs. -13.56 ± 3.22, P = 0.003). DATA CONCLUSION: Compensated increased RV strain, myocardial remodeling of RV, and adverse right and left ventricular interactions occur in rPS patients with preserved RVEF. The decreased interventricular septum strain may lead to impaired LV function due to RV dilation as a result of PR. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020.

19.
Neurosci Lett ; 716: 134630, 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31790718

RESUMO

BACKGROUND: The aim of this study was to investigate the effects of aquaporin 1 (AQP1) knockdown on allodynia in rats with chronic compression of the dorsal root ganglia (DRG) and the role of TRPV4 in these effects. METHODS: Adult male Wistar rats were subjected to chronic compression of the dorsal root ganglia (CCD) via surgery. Behavioral tests were performed to calculate the paw withdrawal mechanical threshold (PWMT). Gene silence was induced by injecting rats with lentivirus expressing AQP1 short hairpin RNA (shRNA, Lv-shAQP1). Western blot analyses were performed to examine AQP1 and TRPV4 protein expression. The concentration of cyclic guanosine monophosphate (cGMP) was determined via enzyme-linked immunosorbent assay. RESULTS: AQP1 protein levels in DRG neurons were significantly increased in CCD rats and were accompanied by a decrease in the PWMT. Lentivirus-mediated RNA interference of AQP1 decreased AQP1 protein expression in CCD rats and normalized their PWMT, but not in rats infected with lentivirus-expressing negative control short hairpin RNA. Furthermore, AQP1 was identified as a cGMP-gated channel. cGMP concentration was upregulated in CCD rats. This effect was attenuated by treatment with a cGMP inhibitor. Additionally, the cGMP inhibitor decreased the mechanical allodynia and AQP1 protein expression in CCD rats. Finally, levels of TRPV4 expression were upregulated in DRG neurons and the L4/L5 spinal cord following surgery, and these effects were reversed by treatment with Lv-shAQP1 or a cGMP inhibitor. CONCLUSION: AQP1 plays a vital role in CCD-induced allodynia as Lv-shAQP1 significantly reduced the allodynia in CCD rats by inhibiting TRPV4 expression.

20.
Nature ; 577(7790): 426-431, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31775157

RESUMO

The organization of genomic DNA into nucleosomes profoundly affects all DNA-related processes in eukaryotes. The histone chaperone known as 'facilitates chromatin transcription' (FACT1) (consisting of subunits SPT16 and SSRP1) promotes both disassembly and reassembly of nucleosomes during gene transcription, DNA replication and DNA repair2. However, the mechanism by which FACT causes these opposing outcomes is unknown. Here we report two cryo-electron-microscopic structures of human FACT in complex with partially assembled subnucleosomes, with supporting biochemical and hydrogen-deuterium exchange data. We find that FACT is engaged in extensive interactions with nucleosomal DNA and all histone variants. The large DNA-binding surface on FACT appears to be protected by the carboxy-terminal domains of both of its subunits, and this inhibition is released by interaction with H2A-H2B, allowing FACT-H2A-H2B to dock onto a complex containing DNA and histones H3 and H4 (ref. 3). SPT16 binds nucleosomal DNA and tethers H2A-H2B through its carboxy-terminal domain by acting as a placeholder for DNA. SSRP1 also contributes to DNA binding, and can assume two conformations, depending on whether a second H2A-H2B dimer is present. Our data suggest a compelling mechanism for how FACT maintains chromatin integrity during polymerase passage, by facilitating removal of the H2A-H2B dimer, stabilizing intermediate subnucleosomal states and promoting nucleosome reassembly. Our findings reconcile discrepancies regarding the many roles of FACT and underscore the dynamic interactions between histone chaperones and nucleosomes.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA