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1.
Dig Dis ; 42(4): 292-298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599188

RESUMO

INTRODUCTION: Clarithromycin resistance is a crucial factor in the eradication of Helicobacter pylori. This study aimed to evaluate the performance of MmaxSure™ H. pylori & ClaR Assay (MmaxSure™) in the diagnosis and detection of clarithromycin resistance in H. pylori. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and October 2022 were enrolled. The diagnostic performances of MmaxSure™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with the rapid urease test and culture. Secondary gene sequencing analysis was performed in discordant cases of PCR tests. RESULTS: A total of 156 gastric biopsy samples were analyzed. In H. pylori detection, MmaxSure™ showed a 95.9% sensitivity (95% CI: 90.6-98.6), a 42.7% specificity (95% CI: 26.3-60.7), and a kappa value of 0.457. For the detection of A2143G mutation samples, MmaxSure™ showed a 91.2% sensitivity (95% CI: 76.3-98.1), a 93.4% specificity (95% CI: 87.5-97.1), and a kappa value of 0.804. There were a total of 10 discordant cases compared to gene sequencing in A2143G mutation detection for MmaxSure™. CONCLUSION: In this study, MmaxSure™ showed comparable diagnostic performance to DPO-PCR in the detection of the H. pylori and A2143G mutation. Further research is needed to confirm the clinical effectiveness of the MmaxSure™ assay in H. pylori eradication.


Assuntos
Antibacterianos , Claritromicina , Farmacorresistência Bacteriana , Infecções por Helicobacter , Helicobacter pylori , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Humanos , Farmacorresistência Bacteriana/genética , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Feminino , Masculino , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Adulto , Sensibilidade e Especificidade , Idoso , Reação em Cadeia da Polimerase Multiplex/métodos
2.
J Clin Neurol ; 20(2): 201-207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171499

RESUMO

BACKGROUND AND PURPOSE: Falls are not uncommon even in patients with early stages of Parkinson's disease (PD). The aims of this study were to determine the relationships between gait parameters and falls and identify crucial gait parameters for predicting future falls in patients with de novo PD. METHODS: We prospectively recruited patients with de novo PD, and evaluated their baseline demographics, global cognitive function on the Montreal Cognitive Assessment test, and parkinsonian motor symptoms including their subtypes. Both forward gait (FG) and backward gait (BG) were measured using the GAITRite system. The history of falls in consecutive patients with de novo PD was examined along with 1 year of follow-up data. RESULTS: Among the 76 patients with de novo PD finally included in the study, 16 (21.1%) were classified as fallers. Fallers had slower gait and shorter stride for FG and BG parameters than did non-fallers, while stride-time variability was greater in fallers but only for BG. Multivariable logistic regression analysis revealed that slow gait was an independent risk factor in BG. CONCLUSIONS: Among the patients with de novo PD, gait speed and stride length were more impaired for both FG and BG in fallers than in non-fallers. It was particularly notable that slow BG was significantly associated with future fall risk, indicating that BG speed is a potential biomarker for predicting future falls in patients with early-stage PD.

4.
BMC Microbiol ; 23(1): 155, 2023 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-37237357

RESUMO

BACKGROUND: Identifying clarithromycin resistance is essential for eradicating Helicobacter pylori (HP). Therefore, we evaluated the performance of Allplex™ H.pylori & ClariR Assay (Allplex™) for diagnosing and detecting clarithromycin resistance in HP. METHODS: Subjects who underwent esophagogastroduodenoscopy between April 2020 and August 2021 at Incheon St. Mary's hospital were enrolled in this study. The diagnostic performances of Allplex™ and dual priming oligonucleotide (DPO)-based multiplex polymerase chain reaction (PCR) were compared with sequencing as the gold standard. RESULTS: A total of 142 gastric biopsy samples were analyzed. Gene sequencing revealed 124 HP infections, 42 A2143G mutations, 2 A2142G mutations, one dual mutation, and no A2142C mutation. DPO-PCR showed 96.0% sensitivity and 100.0% specificity for HP detection; the corresponding rates for Allplex™ were 99.2% and 100.0%. DPO-PCR showed 88.3% sensitivity and 82.0% specificity for A2143G mutation, and Allplex™ showed 97.6% and 96.0%. The Cohen's Kappa coefficient for overall test results was 0.56 for DPO-PCR and 0.95 for Allplex™. CONCLUSION: Allplex™ showed comparable diagnostic performance with direct gene sequencing and non-inferior diagnostic performance to DPO-PCR. Further research is required to confirm whether Allplex™ is an effective diagnostic tool for the eradication of HP.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Claritromicina/farmacologia , Helicobacter pylori/genética , Reação em Cadeia da Polimerase em Tempo Real , Infecções por Helicobacter/diagnóstico , Reação em Cadeia da Polimerase Multiplex/métodos , Oligonucleotídeos , Farmacorresistência Bacteriana/genética , RNA Ribossômico 23S/genética , Antibacterianos/farmacologia
5.
Toxics ; 11(3)2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36977054

RESUMO

The sustained growth of the market for ophthalmic medical devices has increased the demand for alternatives to animal testing for the evaluation of eye irritation. The International Organization for Standardization has acknowledged the need to develop novel in vitro tests to replace animal testing. Here, we evaluated the applicability of an alternative method based on a human corneal model to test the safety of ophthalmic medical devices. 2-Hydroxyethyl methacrylate (HEMA) and Polymethyl methacrylate (PMMA), which are used to fabricate contact lenses, were used as base materials. These materials were blended with eye irritant and non-irritant chemicals specified in the OECD Test Guideline (TG) 492 and Globally Harmonized System (GHS) classification. Then, three GLP-certified laboratories performed three replicates using the developed method using 3D reconstructed human cornea epithelium, MCTT HCETM. OECD TG 492 describes the procedure used to evaluate the eye hazard potential of the test chemical based on its ability to induce cytotoxicity in a reconstructed human cornea-like epithelium (RhCE) tissue. Results: The within-laboratory reproducibility (WLR) and between-laboratory reproducibility (BLR) were both 100%. When a polar extraction solvent was used, the sensitivity, specificity, and accuracy were all 100% in each laboratory. When a non-polar extraction solvent was used, the sensitivity was 80%, the specificity was 100%, and the accuracy was 90%. The proposed method exhibited excellent reproducibility and predictive capacity within and between laboratories. Therefore, the proposed method using the MCTT HCETM model could be used to evaluate eye irritation caused by ophthalmic medical devices.

6.
Nanoscale Adv ; 5(4): 1079-1085, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36798504

RESUMO

Recently, high-efficiency III-nitride photonic emitters (PEs) for next-generation displays have been studied. Although micro-light-emitting diodes (µ-LEDs), one of the III-nitride PEs, have attracted considerable attention because of their high efficiency and size flexibility, they have encountered technical limitations such as high defect rate, high processing cost, and low yield. To overcome these drawbacks of µ-LEDs, a lot of research on PEs using one-dimensional (1D) gallium nitride-related nanorods (GNRs) capable of horizontally self-positioning on the electrodes has been carried out. The degree of array of GNRs on the interdigitated electrodes (IDEs) is an important factor in the efficiency of the PEs using GNRs to obtain excellent single-pixel characteristics. Therefore, in this study, we demonstrate that the improved performance of self-arrayed GNRs was realized using the dielectrophoresis technique by changing the thickness of IDEs. In addition, the shape and size of vertically aligned GNRs were controlled by the wet process, and GNR-integrated PEs (GIPEs) were driven by perfectly horizontally self-arrayed GNRs on IDEs. The electroluminescence (EL) intensity of the GIPEs was measured at 4-20 V and showed a maximum intensity value at 15 V. Over the injection voltage at 20 V, the EL intensity decreased due to the high current density of GIPEs. The external quantum efficiency (EQE) property of the GIPEs showed a similar efficiency droop as that of conventional III-nitride PEs.

7.
Korean J Intern Med ; 37(5): 969-978, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35872626

RESUMO

BACKGROUND/AIMS: Recent epidemiologic studies have shown a continued increase in colorectal cancer incidence among younger adults. Little is known about the factors that contribute to the development of young-onset colorectal neoplasia (CRN). METHODS: A cross-sectional analysis was performed for individuals younger than 40 years who underwent colonoscopy in Seoul St. Mary's Hospital and its affiliated health screening center. High-risk CRN was defined as adenoma or sessile serrated lesion ≥ 10 mm, with three or more adenomas, villous histology, high grade dysplasia, or carcinoma. RESULTS: Of these 13,621 included participants, 2,023 (14.9%) had one and more CRN. Young patients with CRN tended to be elderly, male, obese, smoker, having a habit of drinking, and having comorbidities such as hypertension, dyslipidemia, diabetes, and chronic kidney disease. In a multivariate analysis adjusted for age, sex, obesity, smoking status, and alcohol intake, old age (odds ratio [OR], 1.086; 95% confidence interval [CI], 1.054 to 1.119), male sex (OR, 1.748; 95% CI, 1.247 to 2.451), obesity (OR, 1.439; 95% CI, 1.133 to 1.828), and smoking (OR, 1.654; 95% CI, 1.287 to 2.127) were independent risk factors for overall CRN. Obesity and smoking as two modifiable factors increased the risk for high-risk CRN even more than for overall CRN (OR, 1.734; 95% CI, 1.168 to 2.575 and OR, 1.797; 95% CI, 1.172 to 2.753, respectively). CONCLUSION: Obesity and smoking were modifiable risk factors for CRN in young adults. They increased the risk for highrisk CRN even more than for overall CRN. A colonoscopy might be beneficial for young individuals with these factors.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/diagnóstico , Adulto , Fatores Etários , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Estudos Transversais , Humanos , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
8.
Nat Commun ; 13(1): 1862, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-35387996

RESUMO

Near-eye display technology is a rapidly growing field owing to the recent emergence of augmented and mixed reality. Ultrafast response time, high resolution, high luminance, and a dynamic range for outdoor use are all important for non-pixelated, pupil-forming optics. The current mainstream technologies using liquid crystals and organic materials cannot satisfy all these conditions. Thus, finely patterned light-emissive solid-state devices with integrated circuits are often proposed to meet these requirements. In this study, we integrated several advanced technologies to design a prototype microscale light-emitting diode (LED) arrays using quantum dot (QD)-based color conversion. Wafer-scale epilayer transfer and the bond-before-pattern technique were used to directly integrate 5-µm-scale GaN LED arrays on a foreign silicon substrate. Notably, the lithography-level alignment with the bottom wafer opens up the possibility for ultrafast operation with circuit integration. Spectrally pure color conversion and solvent-free QD patterning were also achieved using an elastomeric topographical mask. Self-assembled monolayers were applied to selectively alter the surface wettability for a completely dry process. The final emissive-type LED array integrating QD, GaN, and silicon technology resulted in a 1270 PPI resolution that is far beyond the retinal limit.


Assuntos
Pontos Quânticos , Silício/química
9.
Eur Radiol ; 32(5): 3597-3608, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35064313

RESUMO

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.


Assuntos
Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Imageamento por Ressonância Magnética/métodos , Transtornos Parkinsonianos/diagnóstico por imagem , Estudos Prospectivos , Substância Negra/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
10.
J Mov Disord ; 15(1): 53-57, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34724780

RESUMO

OBJECTIVE: The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period. METHODS: This was a single-arm study in which 12 subjects with Parkinson's disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months. RESULTS: Dance intervention decreased motor scale (Unified Parkinson's Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL. CONCLUSION: Our findings suggest that dance intervention can be a complementary management method for PD patients.

11.
Parkinsonism Relat Disord ; 87: 135-136, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34034154

RESUMO

We report a novel variant of DHDDS mutation in a patient with progressive adult-onset myoclonus ataxia. The mutation in our patient was different from previous reports of denovo mutations in DHDDS in 6 patients who showed tremor-like myoclonus and generalized epilepsy.


Assuntos
Alquil e Aril Transferases/genética , Epilepsias Mioclônicas Progressivas/genética , Epilepsias Mioclônicas Progressivas/fisiopatologia , Idade de Início , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Epilepsias Mioclônicas Progressivas/diagnóstico
12.
J Mov Disord ; 14(3): 208-213, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34030434

RESUMO

OBJECTIVE: The Four Square Step Test (FSST) is a tool that assesses dynamic balance during obstacle step-over. To date, few studies have used the FSST to measure balance in patients with Parkinson's disease (PD). This study aimed to verify that patients with PD, even at the de novo early stage, take more time to perform the FSST and identify which factors, cognitive status or cardinal motor symptoms, are related most to FSST scores. METHODS: Thirty-five newly diagnosed drug-naïve patients with PD and 17 controls completed the FSST. The Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) stage, spatiotemporal gait parameters, and neuropsychological test battery were also assessed in the PD group. RESULTS: Mean FSST performance time was 8.20 ± 1.61 seconds in patients with PD, which was significantly more than the control group (7.13 ± 1.10 seconds, p = 0.018). UPDRS part III total score and H&Y stage were not significantly associated with FSST, but among the UPDRS subscores, only the postural instability/gait disturbance subscore showed a significant association. Regarding the association between FSST and cognition, the Trail Making Test-B and the Color Word Stroop Test showed strongly inverse correlations with FSST (rho = -0.598 and -0.590, respectively). With respect to gait parameters, double support time was significantly associated with FSST score (rho = 0.342, p = 0.044); however, other parameters, including velocity and step length, were not associated with the FSST. CONCLUSION: The FSST can be used in the clinic to assess dynamic balance with cognitive demands even in the early stages of PD.

13.
Cancers (Basel) ; 12(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050643

RESUMO

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer.

14.
Lab Anim Res ; 35: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31463223

RESUMO

BACKGROUND: Although Eriobotrya japonica leaves have been studied as a raw material for various cosmetic products, little is known about the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of Eriobotrya japonica leaf ethanol extract (EJEE). METHODS: This study was conducted to evaluate the anti-oxidant, anti-inflammatory, and anti-melanogenic activities of EJEE using different in vitro models. In addition, we investigated the potential irritation of EJEE to skin and eye using animal alternative tests. RESULTS: The total content of polyphenols, one of the active constituents of EJEE, was analyzed by high-performance liquid chromatography and found to contain 88.68 mg tannic acid equivalent/g. EJEE showed a concentration-dependent 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging activity, and a superoxide dismutase-like activity. The anti-inflammatory effect of 0.5% (w/v) EJEE was demonstrated by a reduction in lipopolysaccharide-induced nitric oxide and tumor necrosis factor-alpha levels in RAW 264.7 cells. EJEE also significantly inhibited melanogenesis in melanocyte stimulating hormone-induced B16F1 cells. EJEE did not show any irritation in skin and eye in animal alternative test. CONCLUSIONS: These results indicate that the EJEE possesses anti-oxidant, anti-inflammatory, and anti-melanogenic activities, while it did not induce toxicity or irritation in neither skin nor eye. Therefore, EJEE can be used as a cosmetic ingredient for skin improvement.

15.
Nanoscale Res Lett ; 11(1): 341, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27448026

RESUMO

In this study, HIV-1 Rev response element (RRE) RNA was detected via an Au-coated vertical silicon nanowire electrode array (VSNEA). The VSNEA was fabricated by combining bottom-up and top-down approaches and then immobilized by artificial peptides for the recognition of HIV-1 RRE. Differential pulse voltammetry (DPV) analysis was used to measure the electrochemical response of the peptide-immobilized VSNEA to the concentration and types of HIV-1 RRE RNA. DPV peaks showed linearity to the concentration of RNA with a detection limit down to 1.513 fM. It also showed the clear different peaks to the mutated HIV-1 RRE RNA. The high sensitivity and selectivity of VSNEA for the detection of HIV-1 RRE RNA may be attributed to the high surface-to-volume ratio and total overlap diffusion mode of ions of the one-dimensional nanowire electrodes.

16.
Proc Natl Acad Sci U S A ; 113(28): 7810-5, 2016 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-27357681

RESUMO

Measurements of voltage changes in response to charge separation within membrane proteins can offer fundamental information on spectroscopically "invisible" steps. For example, results from studies of voltage changes associated with electron and proton transfer in cytochrome c oxidase could, in principle, be used to discriminate between different theoretical models describing the molecular mechanism of proton pumping. Earlier analyses of data from these measurements have been based on macroscopic considerations that may not allow for exploring the actual molecular mechanisms. Here, we have used a coarse-grained model describing the relation between observed voltage changes and specific charge-transfer reactions, which includes an explicit description of the membrane, the electrolytes, and the electrodes. The results from these calculations offer mechanistic insights at the molecular level. Our main conclusion is that previously assumed mechanistic evidence that was based on electrogenic measurements is not unique. However, the ability of our calculations to obtain reliable voltage changes means that we have a tool that can be used to describe a wide range of electrogenic charge transfers in channels and transporters, by combining voltage measurements with other experiments and simulations to analyze new mechanistic proposals.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/química , Modelos Químicos , Transporte de Elétrons
17.
J Chem Theory Comput ; 12(3): 1000-10, 2016 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-26799775

RESUMO

Nonequilibrium pulling simulations have been a useful approach for investigating a variety of physical and biological problems. The major target in the simulations is to reconstruct reliable potentials of mean force (PMFs) or unperturbed free-energy profiles for quantitatively addressing both equilibrium mechanistic properties and contributions from nonequilibrium processes. While several current nonequilibrium methods were shown to be accurate in computing free-energy profiles in systems with relatively simple dynamics, they have proved to be unsuitable in more complicated systems. To extend the applicability of nonequilibrium sampling, we demonstrate a novel method that combines Minh-Adib's bidirectional estimator with nonlinear WHAM equations to reconstruct and assess PMFs from relatively fast pulling trajectories. We test the method in a one-dimensional model system and in a system of an antibiotic gramicidin-A (gA) channel, which is considered a significant challenge for nonequilibrium sampling. We identify key parameters for efficiently performing pulling simulations to improve and ensure the convergence and accuracy of estimated PMFs. We show that a few pulling trajectories of a relatively fast pulling speed v = 10 Å/ns can return a fair estimate of the PMF of a single potassium ion in gA.


Assuntos
Antibacterianos/química , Gramicidina/química , Bicamadas Lipídicas/química , Termodinâmica
18.
J Phys Chem B ; 120(3): 418-32, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26716721

RESUMO

The voltage sensitivity of membrane proteins is reflected in the response of the voltage sensing domains (VSDs) to the changes in membrane potential. This response is implicated in the displacement of positively charged residues, associated with the conformational changes of VSDs. The displaced charges generate nonlinear (i.e., voltage-dependent) capacitance current called the gating current (and its corresponding gating charge), which is a key experimental quantity that characterizes voltage activation in VSMP. However, the relevant theoretical/computational approaches, aimed to correlate the structural information on VSMP to electrophysiological measurements, have been rather limited, posing a broad challenge in computer simulations of VSMP. Concomitant with the development of our coarse-graining (CG) model of voltage coupling, we apply our theoretical framework for the treatments of voltage effects in membrane proteins to modeling the VSMP activation, taking the VSDs (Ci-VSD) derived from the Ciona intestinalis voltage sensitive phosphatase (Ci-VSP) as a model system. Our CG model reproduces the observed gating charge of Ci-VSD activation in several different perspectives. In particular, a new closed-form expression of the gating charge is evaluated in both nonequilibrium and equilibrium ways, while considering the fluctuation-dissipation relation that connects a nonequilibrium measurement of the gating charge to an equilibrium measurement of charge fluctuations (i.e., the voltage-independent linear component of membrane capacitance). In turn, the expression uncovers a novel link that connects an equilibrium measurement of the voltage-independent linear capacitance to a nonequilibrium measurement of the voltage-dependent nonlinear capacitance (whose integral over voltage is equal to the gating charge). In addition, our CG model yields capacitor-like voltage dependent free energy parabolas, resulting in the free energy difference and the free energy barrier for the Ci-VSD activation at "zero" (depolarization) membrane potential. Significantly, the resultant voltage dependent energetics enables a direct evaluation of capacitance-voltage relationship (C-V curve) as well as charge-voltage relationship (Q-V curve) that is in a good agreement with the observed measurement of Ci-VSD voltage activation. Importantly, an extension of our kinetic/thermodynamic model of voltage dependent activation in VSMP allows for novel derivations of voltage-dependent rate constants, whose parameters are expressed by the intrinsic properties of VSMP. These novel closed-form expressions offer a physicochemical foundation for the semiempirical Eyring-type voltage dependent rate equations that have been the cornerstone for the phenomenological (kinetic) descriptions of gating and membrane currents in the mechanistic study of ion channels and transporters. Our extended theoretical framework developed in the present study has potential implications on the roles played by gating charge fluctuations for the spike generations in nerve cells within the framework of the Hodgkin-Huxley-type model.


Assuntos
Ativação do Canal Iônico , Proteínas de Membrana/química , Cinética , Potenciais da Membrana , Termodinâmica
19.
Proteins ; 84(1): 92-117, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26531155

RESUMO

Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several ß-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data.


Assuntos
Proteínas de Membrana/química , Aminoácidos/química , Proteínas da Membrana Bacteriana Externa/química , Bases de Dados de Proteínas , Escherichia coli/química , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Fosfolipases A1/química , Dobramento de Proteína , Estabilidade Proteica , Estrutura Secundária de Proteína , Eletricidade Estática , Termodinâmica
20.
Nanoscale Res Lett ; 10(1): 429, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26518028

RESUMO

The two-dimensional (2D) growth of cubic-structured (silicon) Si nanosheets (SiNSs) was investigated. Freestanding, single-crystalline SiNSs with a thickness of 5-20 nm were grown on various Si substrates under an atmospheric chemical vapor deposition process. Systematic investigation indicated that a diffusion-limited aggregation (DLA) environment that leads to dendritic growth in <110> directions at the initial stage is essential for 2D growth. The kinetic aspects under DLA environments that ascribe to the dendritic and 2D growth were discussed. Under the more dilute conditions made by addition of Ar to the flow of H2, the SiNSs grew epitaxially on the substrates with periodic arrangement at a specific angle depending on the orientation of the substrate. It reveals that SiNSs always grew two dimensionally with exposing (111) surfaces. That is thermodynamically favorable.

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