Activity

In direct patch-clamp experiments, gossypol inhibited the volume-sensitive outwardly rectifying (VSOR) chloride channel in thymocytes and in human HCT116 and HeLa cells, possibly by a mechanism when gossypol molecule with a radius close to the size of channel pore plugs into the narrowest portion of the native VSOR chloride channel. Micromolar gossypol suppressed proliferation of thymocytes, HCT116 and HeLa cells. VSOR blockage may represent new mechanism of anticancer activity of gossypol in addition to its action as a BH3-mimetic.Human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier (BBB) models established to date lack expression of key adhesion molecules involved in immune cell migration across the BBB in vivo. Here, we introduce the extended endothelial cell culture method (EECM), which differentiates hiPSC-derived endothelial progenitor cells to brain microvascular endothelial cell (BMEC)-like cells with good barrier properties and mature tight junctions. Importantly, EECM-BMEC-like cells exhibited constitutive cell surface expression of ICAM-1, ICAM-2, and E-selectin. Pro-inflammatory cytokine stimulation increased the cell surface expression of ICAM-1 and induced cell surface expression of P-selectin and VCAM-1. Co-culture of EECM-BMEC-like cells with hiPSC-derived smooth muscle-like cells or their conditioned medium further increased the induction of VCAM-1. Functional expression of endothelial ICAM-1 and VCAM-1 was confirmed by T-cell interaction with EECM-BMEC-like cells. Taken together, we introduce the first hiPSC-derived BBB model that displays an adhesion molecule phenotype that is suitable for the study of immune cell interactions.The discovery of alternative signaling pathways that regulate cell death has revealed multiple strategies for promoting cell death with diverse consequences at the tissue and organism level. Despite the divergence in the molecular components involved, membrane permeabilization is a common theme in the execution of regulated cell death. In apoptosis, the permeabilization of the outer mitochondrial membrane by BAX and BAK releases apoptotic factors that initiate the caspase cascade and is considered the point of no return in cell death commitment. read more Pyroptosis and necroptosis also require the perforation of the plasma membrane at the execution step, which involves Gasdermins in pyroptosis, and MLKL in the case of necroptosis. Although BAX/BAK, Gasdermins and MLKL share certain molecular features like oligomerization, they form pores in different cellular membranes via distinct mechanisms. Here, we compare and contrast how BAX/BAK, Gasdermins, and MLKL alter membrane permeability from a structural and biophysical perspective and discuss the general principles of membrane permeabilization in the execution of regulated cell death.

Dixon cardiac magnetic resonance fingerprinting (MRF) has been recently introduced to simultaneously provide water T

, water T

, and fat fraction (FF) maps.

To assess Dixon cardiac MRF repeatability in healthy subjects and its clinical feasibility in a cohort of patients with cardiovascular disease.

T1MES phantom, water-fat phantom, 11 healthy subjects and 19 patients with suspected cardiovascular disease.

Prospective.

1.5T, inversion recovery spin echo (IRSE), multiecho spin echo (MESE), modified Look-Locker inversion recovery (MOLLI), T

gradient spin echo (T

-GRASE), 6-echo gradient rewound echo (GRE), and Dixon cardiac MRF.

Dixon cardiac MRF precision was assessed through repeated scans against conventional MOLLI, T

-GRASE, and PDFF in phantom and 11 healthy subjects. Dixon cardiac MRF native T

, T

, FF, postcontrast T

and synthetic extracellular volume (ECV) maps were assessed in 19 patients in comparison to conventional sequences. Measurements in patients were performed in theity than conventional methods in patients.

2.

2.

2.Bistable and stimuli-responsive molecule-based materials are promising candidates for the development of molecular switches and sensors for future technologies. The CN-bridged NH4 [Ni(cyclam)][Fe(CN)6 ]⋅5 H2 On chain exists in two valence states NiII -FeIII (1HT ) and NiIII -FeII (1LT ) and shows unique multiresponsivity under ambient conditions to various stimuli, including temperature, pressure, light, and humidity, which generate measurable response in the form of significant changes in magnetic susceptibility and color. The electron-transfer phase transition 1LT ↔1HT shows room-temperature thermal hysteresis, can be induced by irradiation, and shows high sensitivity to small applied pressure, which shifts it to higher temperatures. Additionally, it can be reversibly turned off by dehydration to the NH4 [NiII (cyclam)][FeIII (CN)6 ]n (1 d) phase, which features the NiII -FeIII valence state over the whole temperature range, but responds to pressure by yielding NiIII -FeII above 1.06 GPa.

For patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer.

A multi-target MLC tracking algorithm was developed that consisted of three steps (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods single-target tracking and no tracking. Treatment simulations of six risk.Biological market theory provides a conceptual framework to analyse trade strategies in symbiotic partnerships. A key prediction of biological market theory is that individuals can influence resource value – meaning the amount a partner is willing to pay for it – by mediating where and when it is traded. The arbuscular mycorrhizal symbiosis, characterised by roots and fungi trading phosphorus and carbon, shows many features of a biological market. However, it is unknown if or how fungi can control phosphorus value when exposed to abrupt changes in their trade environment. We mimicked an economic ‘crash’, manually severing part of the fungal network (Rhizophagus irregularis) to restrict resource access, and an economic ‘boom’ through phosphorus additions. We quantified trading strategies over a 3-wk period using a recently developed technique that allowed us to tag rock phosphate with fluorescing quantum dots of three different colours. We found that the fungus compensated for resource loss in the ‘crash’ treatment by transferring phosphorus from alternative pools closer to the host root (Daucus carota); and stored the surplus nutrients in the ‘boom’ treatment until root demand increased.