Monitoring of the Variation in Pore Sizes of Woven Geotextiles with Uniaxial Tensile Strain

Characteristic pore-opening size O95 or O90 has been widely used in the filter design of woven geotextiles. These manufactured products have different pore size proportions of large pore diameters, medium pore diameters, and small pore diameters, respectively. Therefore, uncertainties still exist regarding the prediction of geotextile pore diameter variations under the uniaxial tensile strain. This paper investigates the variations in five characteristic pore-opening sizes O95, O80, O50, O30, and O10, with uniaxial tensile strain by using the image analysis method. The large pore diameters, medium pore diameters, and small pore diameters show different variation behaviors as the uniaxial tensile strain increases. Fifteen specific pores are selected and then their pore diameter variations are monitored under each tensile strain of 1%. The colorful pore size distribution diagram is a visual way to identify the variation of pores arranged in the tension direction (warp direction) and the direction perpendicular to tensile loads (weft direction). The various pore diameters are proved to agree well with the bell-shaped Gaussian distribution. The results exhibit an accurate prediction of the variation in large pore sizes, medium pore sizes, and small pore sizes, respectively, for all tested woven geotextiles with uniaxial tensile strain.

TRAP1 and cyclophilin D compete at OSCP subunit to regulate enzymatic activity and permeability transition pore opening by F-ATP synthase

Binding of the mitochondrial chaperone TRAP1 to client proteins shapes cell bioenergetic and proteostatic adaptations, but the panel of TRAP1 clients is only partially defined. Here we show that TRAP1 interacts with F-ATP synthase, the protein complex that provides most cellular ATP. TRAP1 competes with the peptidyl-prolyl cis-trans isomerase cyclophilin D (CyPD) for binding to the oligomycin sensitivity-conferring protein (OSCP) subunit of F-ATP synthase, increasing its catalytic activity and counteracting the inhibitory effect of CyPD. Moreover, TRAP1 inhibits opening of the permeability transition pore (PTP) formed by F-ATP synthase and effectively antagonizes the PTP-inducing effect of CyPD, which elicits mitochondrial depolarization and cell death. Consistently, electrophysiological measurements indicate that TRAP1 and CyPD compete in the modulation of channel activity of purified F-ATP synthase, resulting in PTP inhibition and activation, respectively, and outcompeting each other effect on the channel. Moreover, TRAP1 counteracts PTP induction by CyPD, whereas CyPD reverses TRAP1-mediated PTP inhibition. Our data identify TRAP1 as a F-ATP synthase regulator that can influence cell bioenergetics and survival and can be targeted in pathological conditions where these processes are dysregulated, such as cancer.

Use of Nanoparticles as Nanoelectrodes in Contact-Less Cell Membrane Permeabilization by Time-Varying Magnetic Field: A Computational Study

This paper describes a computational approach for the assessment of electric field enhancement by using highly conductive gold nanoparticles (Au NPs) in time-varying electromagnetic fields cell membrane permeabilization, estimating the influence of the presence of Au NPs on transmembrane potential and on the pore opening dynamics. To account for variability and uncertainty about geometries and relative placement and aggregations of the Au NPs, three different NP configurations were considered: spherical Au NPs equally spaced around the cell; cubic Au NPs, for accounting for the possible edge effect, equally spaced around the cell; and spherical Au NPs grouped in clusters. The results show that the combined use of Au NPs and a time-varying magnetic field can significantly improve the permeabilization of cell membranes. The variability of NPs’ geometries and configurations in proximity of the cell membrane showed to have a strong influence on the pore opening mechanism. The study offers a better comprehension of the mechanisms, still not completely understood, underlying cell membrane permeabilization by time-varying magnetic fields.

Molecular structure of an open human KATP channel

KATP channels are metabolic sensors that translate intracellular ATP/ADP balance into membrane excitability. The molecular composition of KATP includes an inward-rectifier potassium channel (Kir) and an ABC transporter–like sulfonylurea receptor (SUR). Although structures of KATP have been determined in many conformations, in all cases, the pore in Kir is closed. Here, we describe human pancreatic KATP (hKATP) structures with an open pore at 3.1- to 4.0-Å resolution using single-particle cryo-electron microscopy (cryo-EM). Pore opening is associated with coordinated structural changes within the ATP-binding site and the channel gate in Kir. Conformational changes in SUR are also observed, resulting in an area reduction of contact surfaces between SUR and Kir. We also observe that pancreatic hKATP exhibits the unique (among inward-rectifier channels) property of PIP2-independent opening, which appears to be correlated with a docked cytoplasmic domain in the absence of PIP2.

AVE0991 Promotes Neuroprotection via Mas/ERK/mPTP Pathway in α-Synuclein A53T Transgenic Mice

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement diseases featured by selective loss of dopaminergic (DA) neurons within the striatum and substantia nigra (SN). Accumulating evidence have indicated that angiotensin-(1-7) (Ang-(1-7)) prevents neuronal damage by binding to its specific receptor Mas in PD. To date, the underlying mechanisms is not known thus far. In the present study, by using α-synuclein A53T transgenic mice (A53T mice), we showed that the neuronal apoptosis in the SN of A53T mice may be attributed to a decrease in Ang-(1-7) levels. Additionally, we revealed that AVE0991, a recently found non-peptide analogue of Ang-(1−7), ameliorated neuronal apoptosis via Mas/ERK pathway in primary DA neurons. More importantly, we provided novel evidence that this beneficial impact was dependent on the suppression of mitochondrial permeability transition pore opening. In conclusion, these findings disclose the neuroprotective impact of Ang-(1−7) in the etiology of PD, and support the application of its nonpeptide analogue AVE0991 in the therapies of this neurodegenerative disease.

Hierarchically 3-D Porous Structure of Silk Fibroin-Based Biocomposite Adsorbent for Water Pollutant Removal

This study explored the tunability of a 3-D porous network in a freeze-dried silk fibroin/soursop seed (SF:SS) polymer composite bioadsorbent. Morphological, physical, electronic, and thermal properties were assessed using scanning electron microscopy, the BET N2 adsorption-desorption test, Fourier transform infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA). A control mechanism of pore opening–closing by tuning the SS fraction in SF:SS composite was found. The porous formation is apparently due to the amount of phytic acid as a natural cross-linker in SS. The result reveals that a large pore radius is formed using only 20% wt of SS in the composite, i.e., SF:SS (4:1), and the fibrous network closes the pore when the SS fraction increases up to 50%, i.e., SF:SS (1:1). The SF:SS (4:1) with the best physical and thermal properties shows an average pore diameter of 39.19 nm, specific surface area of 19.47 m2·g−1, and thermal stability up to ~450 °C. The removal of the organic molecule and the heavy metal was assessed using crystal violet (CV) dye and the Cu2+ adsorption test, respectively. The adsorption isotherm of both CV and Cu2+ on SF:SS (4:1) follows the Freundlich model, and the adsorption kinetic of CV follows the pseudo-first-order model. The adsorption test indicates that physisorption dominates the adsorption of either CV or Cu2+ on the SF:SS composites.

Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

Ligand binding to membrane proteins is critical for many biological signaling processes. However, individual binding events are rarely directly observed, and their asynchronous dynamics are occluded in ensemble-averaged measures. For membrane proteins, single-molecule approaches that resolve these dynamics are challenged by dysfunction in non-native lipid environments, lack of access to intracellular sites, and costly sample preparation. Here, we introduce an approach combining cell-derived nanovesicles, microfluidics, and single-molecule fluorescence colocalization microscopy to track individual binding events at a cyclic nucleotide-gated TAX-4 ion channel critical for sensory transduction. Our observations reveal dynamics of both nucleotide binding and a subsequent conformational change likely preceding pore opening. Kinetic modeling suggests that binding of the second ligand is either independent of the first ligand or exhibits up to ~10-fold positive binding cooperativity. This approach is broadly applicable to studies of binding dynamics for proteins with extracellular or intracellular domains in native cell membrane.