Scaling and Alpha-Helix Regulation of Protein Relaxation in a Lipid Bilayer

Protein conformation and orientation in the lipid membrane plays a key role in many cellular processes. Here we use molecular dynamics simulation to investigate the relaxation and C-terminus diffusion of a model helical peptide: beta-amyloid (Aβ) in a lipid membrane.We observed that after the helical peptide was initially half-embedded in the extracelluar leaflet of phosphatidylcholine (PC) or PC/cholesterol (PC/CHOL) membrane, the C-terminus diffused across the membrane and anchored to PC headgroups of the cytofacial lipid leaflet. In some cases, the membrane insertion domain of the Aβ was observed to partially unfold. Applying a sigmoidal fit to the process, we found that the characteristic velocity of the C-terminus, as it moved to its anchor site, scaled with θu −4/3, where θu is the fraction of the original helix that was lost during a helix to coil transition. Comparing this scaling with that of bead-spring models of polymer relaxation suggests that the C-terminus velocity is highly regulated by the peptide helical content, but that it is independent of the amino acid type. The Aβ was stabilized by the attachment of the positive Lys28 side chain to the negative phosphate of PC or 3β oxygen of CHOL in the extracellular lipid leaflet and of the C-terminus to its anchor site in the cytofacial lipid leaflet

Evolution of Interlayer Coupling in Twisted MoS2 Bilayers

Van der Waals (vdW) coupling is emerging as a powerful method to engineer and tailor physical properties of atomically thin two-dimensional (2D) materials. In graphene/graphene and graphene/boron-nitride structures it leads to interesting physical phenomena ranging from new van Hove singularities1-4 and Fermi velocity renormalization5, 6 to unconventional quantum Hall effects7 and Hofstadter's butterfly pattern8-12. 2D transition metal dichalcogenides (TMDCs), another system of predominantly vdW-coupled atomically thin layers13, 14, can also exhibit interesting but different coupling phenomena because TMDCs can be direct or indirect bandgap semiconductors15, 16. Here, we present the first study on the evolution of interlayer coupling with twist angles in as-grown MoS2 bilayers. We find that an indirect bandgap emerges in bilayers with any stacking configuration, but the bandgap size varies appreciably with the twist angle: it shows the largest redshift for AA- and AB-stacked bilayers, and a significantly smaller but constant redshift for all other twist angles. The vibration frequency of the out-of-plane phonon in MoS2 shows similar twist angle dependence. Our observations, together with ab initio calculations, reveal that this evolution of interlayer coupling originates from the repulsive steric effects, which leads to different interlayer separations between the two MoS2 layers in different stacking configurations

Molecular Dynamics Simulations Reveal the Protective Role of Cholesterol in β-Amyloid Protein-Induced Membrane Disruptions in Neuronal Membrane Mimics

Interactions of β-amyloid (Aβ) peptides with neuronal membranes have been associated with the pathogenesis of Alzheimer\u27s disease (AD); however, the molecular details remain unclear. We used atomistic molecular dynamics (MD) simulations to study the interactions of Aβ40 and Aβ42 with model neuronal membranes. The differences between cholesterol-enriched and depleted lipid domains were investigated by the use of model phosphatidylcholine (PC) lipid bilayers with and without 40 mol % cholesterol. A total of 16 independent 200 ns simulation replicates were investigated. The surface area per lipid, bilayer thickness, water permeability barrier, and lipid order parameter, which are sensitive indicators of membrane disruption, were significantly altered by the inserted state of the protein. We conclude that cholesterol protects Aβ-induced membrane disruption and inhibits β-sheet formation of Aβ on the lipid bilayer. The latter could represent a two-dimensional (2D) seeding template for the formation of toxic oligomeric Aβ in the pathogenesis of AD

Response law and indicator selection of seismic wave velocity for coal seam outburst risk

The accurate detection of coal seam stress field effectively prevents coal and gas outbursts. This study uses wave velocity, wave velocity anomaly coefficient, and wave velocity gradient as indicators to identify stress anomalies in coal seam. The results show that these three indicators of wave velocity are all positively correlated with load, while changes in the wave velocity anomaly coefficient and wave velocity gradient are more gentle than those of wave velocity. The degree of damage of coal can be judged by the wave velocity anomaly coefficient, while the transition between high and low stress zones can be identified by the wave velocity gradient. In areas affected by geological structures such as valleys and mountain tops, the coal seam wave velocity and wave velocity anomaly coefficient may exhibit anomalies. The comparative analysis of wave velocity and its derived indicators can reveal the stress state and coal structure of coal seam with higher accuracy, identify the areas affected by geological structures such as valleys and mountain tops, and determine the boundary of the stress relief zone after hydraulic fracturing. Combined with the actual geological structure characteristics of coal seam, it can accurately identify the stress disturbance region of coal seam and achieve the purpose of predicting coal and gas outbursts.Document Type: Original articleCited as: Qiu, L., Zhu, Y., Liu, Q., Guo, M., Song, D., Wang, A. Response law and indicator selection of seismic wave velocity for coal seam outburst risk. Advances in Geo-Energy Research, 2023, 9(3): 198-210. https://doi.org/10.46690/ager.2023.09.0

Case report: Clinical and histopathological characteristics of psoriasiform erythema and de novo IL-17A cytokines expression on lesioned skin in atopic dermatitis children treated with dupilumab

BackgroundAtopic dermatitis (AD) is a chronic recurrent inflammatory disease, and dupilumab, a human monoclonal antibody, is the firstly approved biological drug for AD. Psoriasiform erythema (PE) during dupilumab treatment in adults has been reported. This study describes the risk of PE in children after initiation of dupilumab treatment.ObjectivesTo evaluate the de novo cytokines gene expression in the transition of atopic dermatitis symptoms to psoriasiform erythema during dupilumab treatment in children.MethodsTwo 17-year-old teenage twin patients with AD were included in this study who developed psoriasiform erythema after initiation of dupilumab. The lesional skin biopsy specimens were obtained for the histopathological investigation and RNA Fluorescence In Situ Hybridization (RNA-FISH). Dermoscopy, cytometry (cytokine detection in the blood), and blood investigations were completed for the pedigree and the lesioned descriptions.ResultsTwo twin patients with AD presented with erythematic scaly plaques on the back, scalp, abdomen, and extensor extremities after 20 weeks of dupilumab treatment. The transitional change of AD to psoriasiform erythema treated with dupilumab was observed. Our subjects' dermoscopy showed pinpoint bleeding and white scales on pink background. Histopathology features showed psoriasiform hyperplasia, epidermal hyperplasia (acanthosis), ectatic capillaries, perivascular lymphocytes infiltration, and parakeratosis, with the absence of the granular cell layer. mRNA (RNA-FISH) cytokines gene expression showed a significantly high concentration of IL-17A. Blood investigation results showed a high concentration of (Immunoglobulin E) IgE and Eosinophils, and cytokines detection in blood showed IL-5,6 and IL-17 in one patient; however, only IL-5 in another patient. The dupilumab was discontinued and initiated with Baricitinib. Baricitinib showed a significant reduction in skin lesions.ConclusionPsoriasiform erythema can appear during dupilumab treatment in atopic dermatitis children. Potently, by suppressing skewed Th2 activation in patients with AD, the balance might shift toward Th1/Th17 predominance, and psoriasis develops. Baricitinib is a potential drug for psoriasiform erythema with significant therapeutic effects

A tight binding and k.p study of monolayer stanene

Stanene is a single layer of tin atoms which has been discovered as an emerging material for quantum spin Hall related applications. In this paper, we present an accurate tight-binding model for single layer stanene near the Fermi level. We parameterized the onsite and hopping energies for the nearest, second nearest, and third nearest neighbor tight-binding method, both without and with spin orbital coupling. We derived the analytical solution for the →Γ and .→K points and numerically investigated the buckling effect on the material electronic properties. In these points of the reciprocal space, we also discuss a corresponding →k . →p description, obtaining the value of the →k . →p parameters both analytically from the tight-binding ones, and numerically, fitting the ab-initio dispersion relations. Our models provide a foundation for large scale atomistic device transport calculations

The method of coal and gas outburst risk zones division based on quantitative coupling of gas and stress

In order to realize the accurate division of coal and gas outburst risk zones, taking Juji Coal Mine as the case study, the method of coal and gas outburst risk zones division based on quantitative coupling of gas and stress is proposed. The results show that the high gas pressure zones are concentrated in the eastern of No.23 mining area, and most of No.26 and No.27 mining area. The vertical stress in the mine ranges from 6 MPa to 36 MPa. The comprehensive weights of gas pressure and stress are determined by AHP-entropy weight method, and the outburst risk comprehensive index Q is calculated accordingly. According to the range of Q, the mine is divided into low risk zone (Q \u3c 0.5), medium risk zone (0.5 ≤ Q ≤ 0.75) and high risk zone (Q \u3e 0.75). It has been verified that the drilling cuttings S value in No.26 mining area (high risk zone), No.27 mining area (medium risk zone) and No.211 mining area (low risk zone) is 3.6~4.8 kg/m, 3.2~4.6 kg/m and 3.0~4.4 kg/m, and the initial gas emission velocity q value ranged from 0 to 3.7 L/min, 0 to 0.46 L/min and 0 L/min, respectively

Determination of six fluoroquinolones in aquatic products by QuEChERS-ultra performance liquid chromatography-tandem mass spectrometry

Objective To establish a method for the determination of norfloxacin, ciprofloxacin, lomefloxacin, enrofloxacin, ofloxacin and pefloxacin in aquatic products by QuEChERS with ultra performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS). Methods Six fluoroquinolones in aquatic products were extracted by 1% formic acid acetonitrile solution, purified by QuEChERS, separated by C18 column (2.1 mm×100 mm, 1.7 μm) using 0.1% formic acid and methanol-acetonitrile (4∶6, V/V) as mobile phases, then identified and quantified by UPLC-MS/MS. Results Norfloxacin, ciprofloxacin, lomefloxacin, enrofloxacin, ofloxacin and pefloxacin had good linear relationships in a certain concentration range with correlation coefficients (r) above 0.999. The limits of detection of six fluoroquinolones were 0.30-0.80 μg/kg, and limits of quantification were 1.0-2.5 μg/kg. The average recoveries of the method were between 86.6% and 120%, and the relative standard deviations were between 0.59% and 7.6%. Conclusion The method was rapid and accurate, and was suitable for rapid screening and analysis of the six fluoroquinolones in aquatic products