Interaction between single molecules of Mac-1 and ICAM-1 in living cells: an atomic force microscopy study

The interaction between integrin macrophage differentiation antigen associated with complement three receptor function (Mac-1) and intercellular adhesion molecule-1 (ICAM-1), which is controlled tightly by the ligand-binding activity of Mac-1, is central to the regulation of neutrophil adhesion in host defense. Several "inside-out" signals and extracellular metal ions or antibodies have been found to activate Mac-1, resulting in an increased adhesiveness of Mac-1 to its ligands. However, the molecular basis for Mac-1 activation is not well understood yet. In this work, we have carried out a single-molecule study of Mac-1/ICAM-1 interaction force in living cells by atomic force microscopy (AFM). Our results showed that the binding probability and adhesion force of Mac-1 with ICAM-1 increased upon Mac-1 activation. Moreover, by comparing the dynamic force spectra of different Mac-1 mutants, we expected that Mac-1 activation is governed by the downward movement of its alpha7 helix.     

Dynamic domains and geometrical properties of HIV-1 gp120 during conformational changes induced by CD4 binding

The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry. Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen 17b, and the SIV gp120 core pre-bound by the CD4 are known. We have performed dynamic domain studies on the homology models of the CD4-bound and unliganded HIV-1 gp120 with modeled V3 and V4 loops to explore details of conformational changes, hinge axes, and hinge bending regions in the gp120 structures upon CD4 binding. Four dynamic domains were clustered and intricately motional modes for domain pairs were discovered. Together with the detailed comparative analyses of geometrical properties between the unliganded and liganded gp120 models, an induced fit model was proposed to explain events accompanying the CD4 engagement to the gp120, which provided new insight into the dynamics of the molecular induced binding mechanism that complements the molecular dynamics and crystallographic studies.     

Age-related fatigability in knee extensors and knee flexors during dynamic fatiguing contractions

This study investigated the effects of dynamic knee extension and flexion fatiguing task on torque and neuromuscular responses in young and older individuals. Eighteen young (8 males; 25.1 ± 3.2 years) and 17 older (8 males; 69.7 ± 3.7 years) volunteered. Following a maximal voluntary isometric contraction test, participants performed a fatiguing task involving 22 maximal isokinetic (concentric) knee extension and flexion contractions at 60°/s, while surface EMG was recorded simultaneously from the knee extensors (KE) and flexors (KF). Fatigue-induced relative torque reductions were similar between age groups for KE (peak torque decrease: 25.15% vs 26.81%); however, KF torque was less affected in older individuals (young vs older peak torque decrease: 27.6% vs 11.5%; p < 0.001) and this was associated with greater increase in hamstring EMG amplitude (p < 0.001) and hamstrings/quadriceps peak torque ratio (p < 0.01). Furthermore, KE was more fatigable than KF only among older individuals (peak torque decrease: 26.8% vs 11.5%; p < 0.001). These findings showed that the age-related fatigue induced by a dynamic task was greater for the KE, with greater age-related decline in KE compared to KF.     

Predicted threshold against forward and backward loss of balance for perturbed walking

The biomechanical mechanisms of loss of balance have been studied before for slip condition but have not been investigated for arbitrary perturbation profiles under non-slip conditions in sagittal plane. This study aimed to determine the thresholds of center of mass (COM) velocity and position relative to the base of support (BOS) that predict forward and backward loss of balance during walking with a range of BOS perturbations. Perturbations were modeled as sinusoidal BOS motions in the vertical or anterior-posterior direction or as sagittal rotation. The human body was modeled using a seven-link model. Forward dynamics alongside with dynamic optimization were used to find the thresholds of initial COM velocity for each initial COM position that would predict forward or backward loss of balance. The effects of perturbation frequency and amplitude on these thresholds were modeled based on the simulation data. Experimental data were collected from 15 able-bodied individuals and three individuals with disability during perturbed walking. The simulation results showed similarity with the stability region reported for slip and non-slip conditions. The feasible stability region shrank when the perturbation frequency and amplitude increased, especially for larger initial COM velocities. 89.5% (70.9%) and 82.4% (68.2%) of the measured COM position and velocity combinations during low (high) perturbations were located inside the simulated limits of the stability region, for able-bodied and disabled individuals, respectively. The simulation results demonstrated the effects of different perturbation levels on the stability region. The obtained stability region can be used for developing rehabilitative programs in interactive environments.     

Two-year changes in corneal stiffness parameters after accelerated corneal cross-linking

The objective of this non-randomized trial was comparison of two-year changes in dynamic corneal response (DCR) between 18 mW/cm² (5- min) and 9 mW/cm² (10-min) cross-linking (CXL) protocols, using novel stiffness parameters and correlating them to clinical indices. The two groups were evaluated before and 2 years after the procedure using Corvis ST (Oculus Optikgeräte GmbH, Germany) and DCR parameters such as deformation amplitude ratio at 1 mm and 2 mm (DA ratio-1 mm and DA ratio-2 mm) and integrated radius and stiffness parameters at A1 (SP-A1). Two-year follow-up was completed for 16 of the 30 eyes in the 5-min group and 21 of the 25 eyes in the 10-min group; data from those who were lost to follow-up was not included in the analyses. Mean age at baseline was 21.7 ± 4.9 and 21.5 ± 5.2 years in the 5- and 10-min groups, respectively (P = 0.895). At 2 years after CXL, in the 5-min group, the reduction in integrated radius (−1.12 ± 1.27 mm, P = 0.003) was significant, and the increase in SP-A1 (7.11 ± 14.86 mmHg/mm, P = 0.075) was borderline, while in the 10-min group, the decrease in DA ratio-2 mm (−0.43 ± 0.58, P = 0.003) and integrated radius (−1.89 ± 1.72 mm, P < 0.001), and increase in SP-A1 (7.67 ± 10.92 mmHg/mm, P = 0.004) were significant. In both groups, the strongest and significant correlation was observed between DCR parameters and changes in radius of curvature. In conclusion, results indicated corneal strengthening with both protocols especially with the 9 mW/cm². Corvis ST indices can provide “in vivo” biomechanical evidence on the efficacy of CXL that may occur prior to clinical indices.     

Investigation of left heart flow using a numerical correlation to model heart wall motion

A three-dimensional computational fluid dynamics (CFD) method has been developed to model the flow in the left heart including atrium and ventricle. Since time resolution of the medical scans does not fit the requirements of the CFD calculations, the main challenge in a numerical simulation of heart chambers is wall motion modeling. This study employs a novel three-dimensional approximation scheme to correlate the wall boundary and grid movement in systole and diastole. It uses a geometry extracted from medical images in the literature and deformed based on the reported flow rates. The opening and closing of the mitral (MV) and the aortic valve (AV) considered as simultaneous events. Unstructured tetragonal grids were used for the meshing of the domain. The calculation was performed by a Navier–Stokes solver using the arbitrary Lagrange–Euler (ALE) formulation. Results show that the proposed correlation for the wall motion could predict the main features of heart flows.     

Quantifying personal exposure to air pollution from smartphone‐based location data

Personal exposure assessment is a challenging task that requires both measurements of the state of the environment as well as the individual's movements. In this paper, we show how location data collected by smartphone applications can be exploited to quantify the personal exposure of a large group of people to air pollution. A Bayesian approach that blends air quality monitoring data with individual location data is proposed to assess the individual exposure over time, under uncertainty of both the pollutant level and the individual location. A comparison with personal exposure obtained assuming fixed locations for the individuals is also provided. Location data collected by the Earthquake Network research project are employed to quantify the dynamic personal exposure to fine particulate matter of around 2500 people living in Santiago (Chile) over a 4‐month period. For around 30% of individuals, the personal exposure based on people movements emerges significantly different over the static exposure. On the basis of this result and thanks to a simulation study, we claim that even when the individual location is known with nonnegligible error, this helps to better assess personal exposure to air pollution. The approach is flexible and can be adopted to quantify the personal exposure based on any location‐aware smartphone application.     

近年来乌梁素海疣鼻天鹅种群数量变化及原因分析

为查清内蒙古乌梁素海湖泊湿地疣鼻天鹅(Cygnus olor)繁殖期和秋季迁徙前期种群数量,2014至2017年采用路线统计法和样点统计法对其进行精确计数统计,结合近十余年来的文献数据和监测记录,探讨了种群数量的变化及原因。结果显示,2015至2017年春季繁殖成鸟数量依次为84只、92只、80只,基本稳定;2014至2017年,秋季种群数量依次为411只、302只、281只、153只,逐年减少;近几年适宜繁殖地和觅食地面积不断缩小、天敌偷袭、捡蛋和投毒等因素影响亚成鸟和幼鸟的生存。根据文献和保护区监测数据,1996至2004年种群数量逐年增多,与自然保护区的建立、严禁捡蛋和没收猎枪有关,而2005至2013年因干旱缺水、水域被开发利用、芦苇(Phragmites australis)和宽叶香蒲(Typhalatifolia)面积扩增、水质恶化、富营养化加重等原因种群数量下降。研究表明,近几年乌梁素海被过度开发利用,人为干扰频繁,影响疣鼻天鹅正常繁殖栖息;栖息地的科学管理和严禁捡蛋及投毒行为,对该种群的生存及增长至关重要。     

Predicting CO2 adsorption and reactivity on transition metal surfaces using popular density functional theory methods

ABSTRACT

In this work, with Ni (110) as a model catalyst surface and CO₂ as an adsorbate, a performance study of Density Functional Theory methods (functionals) is performed. CO being a possible intermediate in CO₂ conversion reactions, binding energies of both, CO₂ and CO, are calculated on the Ni surface and are compared with experimental data. OptPBE-vdW functional correctly predicts CO₂ binding energy on Ni (?62?kJ/mol), whereas CO binding energy is correctly predicted by the rPBE-vdW functional (?138?kJ/mol). The difference in computed adsorption energies by different functionals is attributed to the calculation of gas phase CO₂. Three alternate reaction systems based on a different number of C=O double bonds present in the gas phase molecule are considered to replace CO₂. The error in computed adsorption energy is directly proportional to the number of C=O double bonds present in the gas phase molecule. Additionally, both functionals predict similar carbon–oxygen activation barrier (40?kJ/mol) and equivalent C1s shifts for probe species (?2.6?eV for CCH₃ and +1.5?eV CO₃^?), with respect to adsorbed CO₂. Thus, by including a correction factor of 28?kJ/mol for the computed CO₂ gas phase energy, we suggest using rPBE-vdW functional to investigate CO₂ conversion reactions on different metals.