Transmembrane receptor proteins are located in the plasma membranes of biological cells where they exert important functions. Archaerhodopsin (Arch) proteins belong to a class of transmembrane receptor proteins called photoreceptors that react to light. Although the light sensitivity of proteins has been intensely investigated in recent decades, the electrophysiological properties of pore-forming Archaerhodopsin (Arch), as studied in vitro, have remained largely unknown. Here, we formed unsupported bilayers between two channels of a microfluidic chip which enabled the simultaneous optical and electrical assessment of the bilayer in real time. Using a cell-free expression system, we recombinantly produced a GFP (green fluorescent protein) labelled as a variant of Arch-3. The label enabled us to follow the synthesis of Arch-3 and its incorporation into the bilayer by fluorescence microscopy when excited by blue light. Applying a green laser for excitation, we studied the electrophysiological properties of Arch-3 in the bilayer. The current signal obtained during excitation revealed distinct steps upwards and downwards, which we interpreted as the opening or closing of Arch-3 pores. From these steps, we estimated the pore radius to be 0.3 nm. In the cell-free extract, proteins can be modified simply by changing the DNA. In the future, this will enable us to study the photoelectrical properties of modified transmembrane protein constructs with ease. Our work, thus, represents a first step in studying signaling cascades in conjunction with coupled receptor proteins.
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http://dx.doi.org/10.3390/ijms222111981 | DOI Listing |
Anticancer Drugs
August 2024
Department of Thoracic Surgery, Peking University Cancer Hospital Inner Mongolia Hospital.
This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro, investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis.
View Article and Find Full Text PDFNeurology
January 2025
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Background And Objectives: Blood-based biomarkers of amyloid and tau have been shown to predict Alzheimer disease (AD) dementia. Much less is known about their ability to predict risk of mild cognitive impairment (MCI), an earlier disease stage. This study examined whether levels of blood biomarkers of amyloid (Aβ/Aβ ratio), tau (p-tau), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI.
View Article and Find Full Text PDFUrolithiasis
December 2024
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
The early stages of kidney crystal formation involve inflammation and hypoxia-induced cell injury; however, the role of the hypoxic response in kidney crystal formation remains unclear. This study investigated the effects of a prolyl hydroxylase domain inhibitor (roxadustat) on renal calcium oxalate (CaOx) crystal formation through in vitro and in vivo approaches. In the in vitro experiment, murine renal tubular cells (RTCs) were exposed to varying roxadustat concentrations and CaOx crystals.
View Article and Find Full Text PDFChembiochem
December 2024
Hunan University, College of Chemistry and Chemical Engineering, Yuelu, 410082, Changsha, CHINA.
Adeno-associated virus (AAV) has emerged as a powerful and effective tool for the delivery of exogenous genes into various cells or tissues. To improve the gene delivery efficiency, as well as the safety and specificity of AAV's cell-targeting capabilities, extensive investigations have been conducted into its molecular biological characteristics, including capsid structure, cellular tropism, and the mechanisms underlying its entry, replication, DNA packaging, and capsid assembly. Significant differences exist between human and non-human primate AAVs regarding tissue targeting and transduction efficiency.
View Article and Find Full Text PDFPituitary
December 2024
Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS San Raffaele Hospital, Milan, Italy.
Introduction: First-generation somatostatin receptor ligands (fg-SRLs) are the cornerstone of acromegaly treatment. Additional benefits were shown using high dose (HD) or high frequency (HF), relatively short-term regimens. Although several predictors of response to standard dose (SD)-fg-SRLs were reported, outcome biomarkers for HF administration are not yet available.
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