Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 2Citation - Scopus: 1Gliflozins, Sucrose and Flavonoids Are Allosteric Activators of Lecithin-Cholesterol Acyltransferase(Nature Portfolio, 2024) Niemela, Akseli; Giorgi, Laura; Nouri, Sirine; Yurttas, Betul; Rauniyar, Khushbu; Jeltsch, Michael; Koivuniemi, ArtturiLecithin-cholesterol acyltransferase (LCAT) serves as a pivotal enzyme in preserving cholesterol homeostasis via reverse cholesterol transport, a process closely associated with the onset of atherosclerosis. Impaired LCAT function can lead to severe LCAT deficiency disorders for which no pharmacological treatment exists. LCAT-based therapies, such as small molecule positive allosteric modulators (PAMs), against LCAT deficiencies and atherosclerosis hold promise, although their efficacy against atherosclerosis remains challenging. Herein we utilized a quantitative in silico metric to predict the activity of novel PAMs and tested their potencies with in vitro enzymatic assays. As predicted, sodium-glucose cotransporter 2 (SGLT2) inhibitors (gliflozins), sucrose and flavonoids activate LCAT. This has intriguing implications for the mechanism of action of gliflozins, which are commonly used in the treatment of type 2 diabetes, and for the endogenous activation of LCAT. Our results underscore the potential of molecular dynamics simulations in rational drug design.Article Citation - WoS: 9Citation - Scopus: 6Fluorescence Lifetime Multiplexing With Fluorogen Activating Protein Fast Variants(Nature Portfolio, 2024) Bogdanova, Yulia A.; Solovyev, Ilya D.; Baleeva, Nadezhda S.; Myasnyanko, Ivan N.; Gorshkova, Anastasia A.; Gorbachev, Dmitriy A.; Baranov, Mikhail S.In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling. A genetically encoded labeling system uses smallest-in-class fluorogen-activating protein tags for time-resolved fluorescence multiplexed cellular imaging, offering monoexponential decay and potential for sophisticated fluorescence lifetime analysis.Article Citation - WoS: 6Citation - Scopus: 6Tumour-Intrinsic Endomembrane Trafficking by Arf6 Shapes an Immunosuppressive Microenvironment That Drives Melanomagenesis and Response To Checkpoint Blockade Therapy(Nature Portfolio, 2024) Wee, Yinshen; Wang, Junhua; Wilson, Emily C.; Rich, Coulson P.; Rogers, Aaron; Tong, Zongzhong; Grossmann, Allie H.Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy. The small GTPase ARF6 is known to regulate endocytosis and recycling of plasma membrane proteins. Here the authors show that tumourintrinsic ARF6 promotes an immunosuppressive microenvironment that accelerates melanoma progression but that is vulnerable to immune checkpoint blockade, mechanistically linked to ARF6-dependent recycling of interferon-gamma receptors in tumour cells.Article Citation - WoS: 13Citation - Scopus: 13The Influence of Nano Filter Elements on Pressure Drop and Pollutant Elimination Efficiency in Town Border Stations(Nature Portfolio, 2023) Ebadiyan, Hamed; Heris, Saeed Zeinali; Mousavi, Seyed Borhan; Nami, Shamin Hosseini; Mohammadpourfard, MousaNatural gas stands as the most ecologically sustainable fossil fuel, constituting nearly 25% of worldwide primary energy utilization and experiencing rapid expansion. This article offers an extensive comparative analysis of nano filter elements, focusing on pressure drop and pollutant removal efficiency. The primary goal was to assess the superior performance of nano filter elements and their suitability as an alternative for Town Border Station (TBS). The research encompassed a six-month examination period, involving routine pressure assessments, structural examinations, and particle characterization of the filter elements. The results revealed that nano filters showed better performance in adsorbing aluminum than conventional filters, possibly due to their cartridge composition. Nano filters contained phosphorus, sulfur, and copper, while conventional filters lacked these elements. The disparity can be attributed to the finer mesh of the nano filter, capturing smaller pollutants. Although the nano filter had minimal silicon, the conventional filter showed some, posing concerns. Despite having 19 extra pleats, the nano filter maintained gas flow pressure while capturing more particles than the conventional filter.Article Citation - WoS: 75Citation - Scopus: 73Proton Transport Through Nanoscale Corrugations in Two-Dimensional Crystals(Nature Portfolio, 2023) Wahab, O. J.; Daviddi, E.; Xin, B.; Sun, P. Z.; Griffin, E.; Colburn, A. W.; Unwin, P. R.Defect-free graphene is impermeable to all atoms(1-5) and ions(6,7) under ambient conditions. Experiments that can resolve gas flows of a few atoms per hour through micrometre-sized membranes found that monocrystalline graphene is completely impermeable to helium, the smallest atom(2,5). Such membranes were also shown to be impermeable to all ions, including the smallest one, lithium(6,7). By contrast, graphene was reported to be highly permeable to protons, nuclei of hydrogen atoms(8,9). There is no consensus, however, either on the mechanism behind the unexpectedly high proton permeability(10-14) or even on whether it requires defects in graphene's crystal lattice(6,8,15-17). Here, using high-resolution scanning electrochemical cell microscopy, we show that, although proton permeation through mechanically exfoliated monolayers of graphene and hexagonal boron nitride cannot be attributed to any structural defects, nanoscale non-flatness of two-dimensional membranes greatly facilitates proton transport. The spatial distribution of proton currents visualized by scanning electrochemical cell microscopy reveals marked inhomogeneities that are strongly correlated with nanoscale wrinkles and other features where strain is accumulated. Our results highlight nanoscale morphology as an important parameter enabling proton transport through two-dimensional crystals, mostly considered and modelled as flat, and indicate that strain and curvature can be used as additional degrees of freedom to control the proton permeability of two-dimensional materials. A study using high-resolution scanning electrochemical cell microscopy attributes proton permeation through defect-free graphene and hexagonal boron nitride to transport across areas of the structure that are under strain.