Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.133
Filtrar
1.
Mol Med Rep ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922235

RESUMO

Bromodomain­containing 4 (BRD4) is a histone modification reader and transcriptional regulator that has been reported to interact with acetylated lysine histone motifs transcription factors (TFs), transcription co­activators and RNA polymerase II. The selective small molecule inhibitor JQ1, which binds competitively to bromodomains, has been reported to exhibit anti­proliferative effects in various types of cancer. Previous studies on the mechanism of action of JQ1 mostly focused on a specific tumor type or disease; however, the general mechanism through which JQ1 affects various tumors remains to be determined. In the present study, chromatin immunoprecipitation sequencing data for BRD4 and its expression profiles in six cancer cell lines were integrated and analyzed systematically. The results indicated that BRD4 binds to enhancers with histone H3 acetylated at lysine 27 (H3K27Ac) and mediator complex subunit 1 in a cell type­specific manner, as well as binds to promoter regions with the oncogenic TFs MYC and E2F1 in a cell type­common manner. The cell type­common sites across the six cell types investigated were found to be functionally important for tumorigenesis, whereas the cell type­specific sites were functionally enriched with the cell identity, all of which were sensitive to JQ1 treatment. Furthermore, a core set of JQ1­regulated BRD4 binding genes were obtained, which were significantly inhibited by JQ1 in various cancer cell lines and contributed to hallmarks of cancer. These results implied a common mechanism underlying the therapeutic effects of JQ1 and suggested its potential suitability as an anti­cancer drug targeting BRD4­mediated transcriptional regulation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31922385

RESUMO

Lithium metal is among the most promising anode candidate of the high-energy battery. However, the formed dendrites result in low Coulombic efficiency and serious security issues. Designing lithiophilic sites is one of the effective strategies to control Li deposition. Herein, we propose a three-dimensional lithiophilic N-rich carbon nanofibers with the decoration of ZnO granules as a protective layer for dendrite-free lithium metal anode. Theoretical evaluation indicates the synergistic effects of lithiophilic ZnO and N-containing functional groups enhance the lithium adsorption and trigger the uniform deposition. With the lithiophilic interlayer, lithium deposition overpotential is only ~20, 50, and 74 mV at 1, 3, and 6 mA cm-2, respectively, which are much lower than these without the functional interlayer (~55, 130, and 238 mV). The Coulombic efficiency of lithium stripping and plating is up to ∼98.0% (92.5% for that without interlayer) after 120 cycles at 0.5 mA cm-2. Meanwhile, the Li|LiFePO4 full cell with the superlithiophilic interlayer demonstrates a high capacity retention rate of 99.6% (91.0% for that without interlayer) over 200 cycles at 1 C. The introduction of lithiophilic interphase could provide a convenient strategy and guidance to design the configuration for the practical application of Li metal batteries.

3.
BMC Psychol ; 8(1): 2, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910907

RESUMO

BACKGROUND: Response inhibition can be classified into stimulus-driven inhibition and intentional inhibition based on the degree of endogenous volition involved. In the past decades, abundant research efforts to study the effects of alcohol on inhibition have focused exclusively on stimulus-driven inhibition. The novel Chasing Memo task measures stimulus-driven and intentional inhibition within the same paradigm. Combined with the stop-signal task, we investigated how alcohol use affects behavioral and psychophysiological correlates of intentional inhibition, as well as stimulus-driven inhibition. METHODS: Experiment I focused on intentional inhibition and stimulus-driven inhibition in relation to past-year alcohol use. The Chasing Memo task, the stop-signal task, and questionnaires related to substance use and impulsivity were administered to 60 undergraduate students (18-25 years old). Experiment II focused on behavioral and neural correlates acute alcohol use on performance on the Chasing Memo task by means of electroencephalography (EEG). Sixteen young male adults (21-28 years old) performed the Chasing Memo task once under placebo and once under the influence of alcohol (blood alcohol concentration around 0.05%), while EEG was recorded. RESULTS: In experiment I, AUDIT (Alcohol Use Disorder Identification Test) total score did not significantly predict stimulus-driven inhibition or intentional inhibition performance. In experiment II, the placebo condition and the alcohol condition were comparable in terms of behavioral indices of stimulus-driven inhibition and intentional inhibition as well as task-related EEG patterns. Interestingly, a slow negative readiness potential (RP) was observed with an onset of about 1.2 s, exclusively before participants stopped intentionally. CONCLUSIONS: These findings suggest that both past-year increases in risky alcohol consumption and moderate acute alcohol use have limited effects on stimulus-driven inhibition and intentional inhibition. These conclusions cannot be generalized to alcohol use disorder and high intoxication levels. The RP might reflect processes involved in the formation of an intention in general.

4.
Neuropharmacology ; : 107934, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926216

RESUMO

The occurrence of major depressive disorder (MDD) has been linked to an increased vulnerability to stress. The basolateral amygdala (BLA) is one of the critical brain areas that involved in the regulation of pathological reactivity to stress. Increasing evidence indicates that the EphB2 receptor (EphB2) plays a critical role in neuropsychiatric disorders, such as Alzheimer's disease, pain and anxiety. However, whether the EphB2 in the BLA is involved in stress vulnerability is unclear. Here, we identified EphB2 in the BLA as a key regulator contributed to the modulation of stress vulnerability in adult mice. We found that the expression of EphB2 in the BLA was significantly increased in the animal model induced by chronic social stress. Knockdown of EphB2 in the BLA produced antidepressant-like behavioral effects, whereas activation of EphB2 in the BLA increased the susceptibility to subthreshold social defeat stress. Furthermore, we demonstrated that the role of EphB2 in the stress vulnerability was mediated by modulating NMDA receptors, since the knockdown of EphB2 in the BLA prevented not only the increase in the amplitudes of both the miniature and the evoked NMDAR-mediated EPSC, but also the enhancement of surface expression of NMDARs in the defeated mice. Taken together, these results suggest that EphB2 in the BLA is a critical factor contributes to the vulnerability to stress, which may be a potential target for the treatment of depression.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31927742

RESUMO

Mesoporous ZSM-5 zeolite (MZ) was used as support for Cu and Ce species, and the effects of structure and physical-chemical properties on selective catalytic reduction of NO with NH3 (NH3-SCR) were investigated. The characterization and experimental results show that the high activity of the Cu-Ce/MZ catalyst could be due to its high surface area, more and uniformly distributed active sites, and abundant oxidative species. Compared with the conventional ZSM-5 and SBA-15, the Cu-Ce/MZ possesses large amount of mesopores, and more accessible active sites, which are beneficial to accelerate the diffusion and improve the internal mass transfer in the denitration process. The Cu-Ce/MZ catalyst shows higher activity than Cu-Ce/ZSM-5 and Cu-Ce/SBA-15 at 200 °C.

6.
Endocrine ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927749

RESUMO

OBJECTIVES: To assess the efficacy and safety of once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) dulaglutide for the treatment of type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We searched PubMed, Embase, and Cochrane Library from inception to August 18, 2019. Revman5.3 and Stata13.0 software were used for meta-analysis. RESULTS: Twenty-one trials including 20,367 patients were analyzed. Compared with control group, hemoglobin A1c (HbA1c) in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group were reduced by 0.29% and 0.55%, respectively. More patients treated with 0.75 mg dulaglutide [RR 1.24, 95% CI (1.08, 1.42), p = 0.002] and 1.5 mg dulaglutide [RR 1.66, 95% CI (1.40, 1.99), p < 0.00001] had reached the target of HbA1c 7.0%. In patients with T2DM, 0.75 mg dulaglutide and 1.5 mg dulaglutide had a statistically higher adverse events (AEs) incidence than control, whereas the risk of hypoglycaemia was lower in 0.75 mg dulaglutide group and 1.5 mg dulaglutide group than in control group. CONCLUSIONS: Based on the current evidence, 0.75 and 1.5 mg dulaglutide are associated with better glycemic control and lower rate of hypoglycemia in patients with T2DM.

7.
Dalton Trans ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895364

RESUMO

With the increasing energy demand, it is very urgent to develop new anode materials for lithium ion batteries (LIBs). Designing nanostructures and constructing multicomponent metal sulfides are vital for enhancing the electrochemical performance. This study reports a new synthetic method to construct MoS2/CoMo2S4/Co3S4 nanostructures supported by graphene. A key step in the process, high temperature annealing, promotes the interdiffusion of metal sulfides to form multicomponent metal sulfides and establishes a strong C-S bond between the MoS2/CoMo2S4/Co3S4 nanostructure and graphene. The unique nanostructure and synergistic effects between the conductive graphene and the MoS2/CoMo2S4/Co3S4 nanostructure endows the material with good lithium storage. As a result, it exhibits a good rate performance (360 mA h g-1 at 10 A g-1) and a high specific capacity (770 mA h g-1 at 0.2 A g-1). This study provides a unique method to construct promising anode materials for the application of LIBs.

8.
Sci Total Environ ; 704: 135413, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31896227

RESUMO

Mountain glaciers retreat at an increased rate under global warming, resulting in exposed barren surfaces for primary succession. Soil microbes are an important driver of ecosystem processes. Although variations in soil microbes after deglaciation have been studied extensively, the roles of rhizosphere soil microbes in the biogeochemistry cycle during primary succession are less understood. In this study, Populus purdomii was present throughout the 123-year chronosequence as a representative tree species. We therefore investigated variations in the rhizosphere enzyme activity, microbial community structure, and ecoenzymatic stoichiometry of P. purdomii along Hailuogou Glacier chronosequences. The objective was to determinechanges in rhizosphere enzyme activities and microbial communities, as well as the effects of nutrient limitation on rhizosphere microbes. According to the results, the enzyme activities and microbial group biomass in rhizosphere soil all showed a bimodal trend and were highest at the 43rd or 123rd year, and enzyme activity varied with succession time but not microbial community structure. The rhizosphere soil bacterial community was the dominant community during the 123-year chronosequence. Ecoenzymatic stoichiometry indicated nitrogen restrictions on microbial activity throughout primary succession, with early succession stages (5-15 years) showing greater carbon restriction than late succession stages. Moreover, redundancy and correlation analyses demonstrated that soil microbial phospholipid fatty acid biomass was an important factor for increases in enzyme activities and that enzyme activities in turn played important roles in carbon, nitrogen and phosphorus cycling in rhizosphere soil. Additionally, rhizosphere soil microbial development significantly affected soil organic carbon, total nitrogen and dissolved organic carbon accumulation. Overall, our study links the rhizosphere microbial community and activity to successional chronosequences, providing a deeper understanding of the dynamics of ecosystem succession.

9.
Nanoscale ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899466

RESUMO

Fluorescence quantum dots (QDs) are promising functional nanomaterials in chemical biology and environmental applications, where an analyte-induced responsive system is beneficial for detecting numerous life-related molecules and pollutants. Here, fluorescent Ti3C2 MXene quantum dots (MQDs) with the size of 1.75 nm were synthesized by a simple method of hydrofluoric acid etching and dimethyl sulfoxide exfoliation to form nanosheets followed by a one-step ultrasound method. The as-synthesized MQDs showed excitation-dependent behaviour along with a fluorescence quantum yield value of 7.7%. In addition, the fluorescence of the MQDs can be significantly suppressed by Fe3+. The mechanism for the fluorescence quenching of the MQDs was systematically investigated, which was attributed to the oxidation-reduction reaction between the MQDs and Fe3+ and the inner filter effect (IFE), different from the reported Förster resonant energy transfer (FRET) mechanism for MXene nanosheets. Based on this trait, a fluorescence method for Fe3+ detection based on MQDs was demonstrated with high sensitivity and selectivity, and the limit of detection was 310 nM. The proposed method was successfully used for the sensitive detection of Fe3+ in serum and sea water. This work will not only help to understand the selectivity mechanisms of MQDs as fluorescent probes for metal ions, but also provide a smart sensing platform in biological and environmental detection.

10.
Nanotechnology ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899897

RESUMO

Core-shell CeO2:Er,Yb@W18O49heterojunction is successfully synthesized via facile solvothermal method. The octahedral CeO2:Er,Yb nanocrystals core exhibit green (2H11/2,4S3/2-4I15/2), red (4F9/2-4I15/2) and NIR (4I11/2-4I15/2and4I13/2-4I15/2) emission under 980 nm laser diode excitation, and the multiband emissions are absorbed by the W18O49nanowires shell to re-excited its higher energy localized surface plasmon resonances (LSPR). With the excitation of 980 nm, the photocatalytic property of CeO2:Er,Yb@W18O49for hydrogen (H2) evolution from ammonia borane (BH3NH3) is researched, which is 3 times increased compared to W18O49. Besides, the application of natural sunlight for H2producing is provided, an obvious H2production enhancement compared to the W18O49(2 times) is also observed. This remarkable enhancement in catalytic activity of CeO2:Er,Yb@W18O49heterostructures is ascribed to re-excitation of LSPR by multiband emissions of CeO2:Er,Yb.

11.
J Neural Eng ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899901

RESUMO

Objective- It is of great value to accurately localize innervation zones (IZs) for better diagnosing and treating neuromuscular diseases, but it is challenging to do so noninvasively from surface electromyography (sEMG) recordings because of the blurring/ distorting effect of the low conductive fat tissues. This study aimed to develop an innovative transcutaneous IZ imaging (TIZI) technique to precisely and efficiently localize the IZ distribution directly over the muscle surface in vivo from high-density sEMG recordings (HD-sEMG). Approach- The TIZI technique was implemented by incorporating HD-sEMG recording, signal decomposition, finite element analysis and inverse calculation. The performance of TIZI was evaluated on the flexor digitorum superficialis (FDS) muscle with simulated sEMG signal and experimental signal recorded from both healthy (n=3) and stroke participants (n=4). The accuracy of imaging was validated by both of the Pearson correlation coefficient (PCC) and localization error (LE) between the TIZI results and the 'true' IZ distribution. Main Results- In the simulation study, results have shown PCCs of 99.85±0.11%, 99.79±0.08%, 99.63±0.22% and 99.31±0.54% at the depth of 10, 15, 20 and 25 mm and SNR of 25 dB. PCCs of 98.74±1.78% and 97.82±1.20% were respectively obtained for experimental signals acquired from the healthy and spastic FDS muscles. The TIZI provided smaller LEs of 1.4±0.92 mm and 2.02 ± 1.3 mm, compared to LEs of 7.42±2.29 mm and 7.8±1.77 mm from skin observations in healthy and spastic FDS, respectively. Significance- Results have demonstrated the high performance of the proposed TIZI technique in transcutaneously imaging the IZ distribution of the skeletal muscles. The performance improvement can be attributed to the elimination of blurring/ distorting effect caused by the low conductive fat and high conductive skin tissues. TIZI may provide an advanced neurological tool for the clinical treatment of neuromuscular diseases, such as guiding botulinum neurotoxin injections in spasticity management.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31904318

RESUMO

A Gram-stain-negative, strictly aerobic, rod-shaped and non-motile bacterial strain, designated D-2Q-5-6T, was isolated from a soil sample collected from the Arctic region. Strain D-2Q-5-6T was found to grow at 10-43 °C (optimum, 28 °C), at pH 6.0-9.0 (pH 7.0) and in 0-5 % (w/v) NaCl (0-1 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D-2Q-5-6T fell into the genus Sphingorhabdus and shared less than 95.8 % identity with all type strains of recognized species of this genus. The major cellular fatty acids of strain D-2Q-5-6T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c; 31.4 %), summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 26.8 %) and C14 : 0 2OH (11.7 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and sphingoglycolipid. The predominant quinone was identified as Q10. The DNA G+C content of strain D-2Q-5-6T was 64.5 mol%. Based on the results of phylogenetic analysis and distinctive phenotypic characteristics, strain D-2Q-5-6T is concluded to represent a novel species of the genus Sphingorhabdus, for which the name Sphingorhabdus soli sp. nov. is proposed. The type strain of the species is D-2Q-5-6T (=MCCC 1A06070T=KCTC 52311T).

14.
Artigo em Inglês | MEDLINE | ID: mdl-31912322

RESUMO

Development and application of advanced mechanical models of soft tissues and their growth represent one of the main directions in modern mechanics of solids. Such models are increasingly used to deal with complex biomedical problems. Prediction of in-stent restenosis for patients treated with coronary stents remains a highly challenging task. Using a finite element method, this paper presents a mechanistic approach to evaluate the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by such intervention. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Narrowing of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. It is demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The larger the artery expansion achieved during balloon inflation, the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. In addition, the development of in-stent restenosis is directly correlated with the artery expansion during the stent deployment. The correlation is further used to predict the effect of a complex clinical procedure, such as stent overlapping, on the level of in-stent restenosis developed after percutaneous coronary intervention.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31913014

RESUMO

Effective ultraviolet light-emitting diodes (LEDs) were fabricated by clamping the n-ZnO films on the top of p-hBN/p-GaN/sapphire substrates. An ultraviolet emission originating from ZnO was measured from the diode under forward bias, the electroluminescence (EL) spectra of which show a peak wavelength of ~376 nm with a narrow full-width at half maximum of ~12 nm. Compared with the reference diode fabricated by directly growing n-ZnO on the p-hBN substrates using metal-organic chemical vapor deposition, the proposed diode showed a dramatic increment of the EL intensity, meanwhile its emission onset lowered down considerably. The improved optical property of the proposed LED is mainly ascribed to suppressing the formation of the BNO-related layer at the n-ZnO/p-hBN interface. The present work provides a simple and feasible approach for developing advanced ZnO-based optoelectronic devices.

16.
Theranostics ; 10(2): 797-815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903151

RESUMO

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs. Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress. Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.

17.
Mol Nutr Food Res ; : e1900535, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31914235

RESUMO

SCOPE: Recent findings indicate that ketogenic diet is neuroprotective and electrical stimulation can improve functional recovery from peripheral nerve injury. However, it is not clear whether ketogenic diet and electrical stimulation play synergistical role in the peripheral nerve recovery following injury. METHODS AND RESULTS: We used ketogenic diet consisting of 3:1 ratio of fat to carbohydrate+protein and coupled it with electrical stimulation treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery was evaluated by electromyography, and axonal regeneration and myelination by histological methods. We also investigated the effects on IGF-1 and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury. Combination of ketogenic diet and electrical stimulation synergistically increased muscle force in biceps femoris and gluteus maximus and prevented development of hypersensitivity in biceps femoris. It promoted peripheral nerve regeneration by increasing total axons, axons density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects were due to modulation of IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. CONCLUSION: Our results establish that ketogenic diet and electrical stimulation promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach. This article is protected by copyright. All rights reserved.

18.
Carcinogenesis ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31917403

RESUMO

The repurposing of existing drugs has emerged as an attractive additional strategy to the development of novel compounds in the fight against cancerous diseases. Inhibition of Phosphodiesterase 5 has been claimed as a potential approach to target various cancer subtypes in recent years. However, data on the treatment of tumors with PDE5 inhibitors as well as the underlying mechanisms are as yet very scarce. Here we report that treatment of tumor cells with low concentrations of Sildenafil was associated with decreased cancer cell proliferation and augmented apoptosis in vitro and resulted in impaired tumor growth in vivo. Notably, incubation of cancer cells with Sildenafil was associated with altered expression of HSP90 chaperone followed by degradation of PKD2, a client protein previously reported to be involved in tumor growth. Furthermore, the involvement of low doses of PU-H71, an HSP90-inhibitor currently under clinical evaluation, in combination with low concentrations of Sildenafil, synergistically and negatively impacted on the viability of cancer cells in vivo. Taken together, our study suggests that repurposing of already approved drugs, alone or in combination with oncology-dedicated compounds, may represent a novel cancer therapeutic strategy.

19.
Pediatr Res ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896126

RESUMO

BACKGROUND: Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. METHODS: Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. RESULTS: The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-ß/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. CONCLUSIONS: The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-ß/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.

20.
Nat Commun ; 11(1): 32, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31896744

RESUMO

Many intracellular pathogens, such as mammalian reovirus, mimic extracellular matrix motifs to specifically interact with the host membrane. Whether and how cell-matrix interactions influence virus particle uptake is unknown, as it is usually studied from the dorsal side. Here we show that the forces exerted at the ventral side of adherent cells during reovirus uptake exceed the binding strength of biotin-neutravidin anchoring viruses to a biofunctionalized substrate. Analysis of virus dissociation kinetics using the Bell model revealed mean forces higher than 30 pN per virus, preferentially applied in the cell periphery where close matrix contacts form. Utilizing 100 nm-sized nanoparticles decorated with integrin adhesion motifs, we demonstrate that the uptake forces scale with the adhesion energy, while actin/myosin inhibitions strongly reduce the uptake frequency, but not uptake kinetics. We hypothesize that particle adhesion and the push by the substrate provide the main driving forces for uptake.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA