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Nature Cell Biology Jul 2024α-Synuclein (α-Syn) aggregation is closely associated with Parkinson's disease neuropathology. Physiologically, α-Syn promotes synaptic vesicle (SV) clustering and...
α-Synuclein (α-Syn) aggregation is closely associated with Parkinson's disease neuropathology. Physiologically, α-Syn promotes synaptic vesicle (SV) clustering and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly. However, the underlying structural and molecular mechanisms are uncertain and it is not known whether this function affects the pathological aggregation of α-Syn. Here we show that the juxtamembrane region of vesicle-associated membrane protein 2 (VAMP2)-a component of the SNARE complex that resides on SVs-directly interacts with the carboxy-terminal region of α-Syn through charged residues to regulate α-Syn's function in clustering SVs and promoting SNARE complex assembly by inducing a multi-component condensed phase of SVs, α-Syn and other components. Moreover, VAMP2 binding protects α-Syn against forming aggregation-prone oligomers and fibrils in these condensates. Our results suggest a molecular mechanism that maintains α-Syn's function and prevents its pathological amyloid aggregation, the failure of which may lead to Parkinson's disease.
PubMed: 38951706
DOI: 10.1038/s41556-024-01456-1 -
Nature Reviews. Molecular Cell Biology Jul 2024
PubMed: 38951704
DOI: 10.1038/s41580-024-00759-3 -
Nature Materials Jul 2024The voltage penalty driving water dissociation (WD) at high current density is a major obstacle in the commercialization of bipolar membrane (BPM) technology for energy...
The voltage penalty driving water dissociation (WD) at high current density is a major obstacle in the commercialization of bipolar membrane (BPM) technology for energy devices. Here we show that three materials descriptors, that is, electrical conductivity, microscopic surface area and (nominal) surface-hydroxyl coverage, effectively control the kinetics of WD in BPMs. Using these descriptors and optimizing mass loading, we design new earth-abundant WD catalysts based on nanoparticle SnO synthesized at low temperature with high conductivity and hydroxyl coverage. These catalysts exhibit exceptional performance in a BPM electrolyser with low WD overvoltage (η) of 100 ± 20 mV at 1.0 A cm. The new catalyst works equivalently well with hydrocarbon proton-exchange layers as it does with fluorocarbon-based Nafion, thus providing pathways to commercializing advanced BPMs for a broad array of electrolysis, fuel-cell and electrodialysis applications.
PubMed: 38951650
DOI: 10.1038/s41563-024-01943-8 -
Communications Biology Jul 2024The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological...
The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.
Topics: Animals; Mice; Mice, Knockout; Integrin beta3; Cell Membrane; Regeneration; Myocytes, Cardiac; Male; Plasmalogens; Signal Transduction; Myocardium; Mice, Inbred C57BL; Heart Injuries; Cell Proliferation; Membrane Proteins
PubMed: 38951640
DOI: 10.1038/s42003-024-06483-0 -
Scientific Reports Jul 2024Acoustic metamaterials are growing in popularity for sound applications including noise control. Despite this, there remain significant challenges associated with the...
Acoustic metamaterials are growing in popularity for sound applications including noise control. Despite this, there remain significant challenges associated with the fabrication of these materials for the sub-100 Hz regime, because acoustic metamaterials for such frequencies typically require sub-mm scale features to control sound waves. Advances in additive manufacturing technologies have provided practical methods for rapid fabrication of acoustic metamaterials. However, there is a relatively high sensitivity of their resonant characteristics to sub-mm deviations in geometry, pushing the limits of additive manufacturing. One way of overcoming this is via active control of device resonance. Here, an acoustic metamaterial cell with adjustable resonance is demonstrated for the sub-100 Hz regime. A functionally superparamagnetic membrane-devised to facilitate the fabrication process by eliminating magnetic poling requirements-is engineered using stereolithography, and its mechanical and acoustic properties are experimentally measured using laser Doppler vibrometry and electret microphone testing, with a mathematical model developed to predict the cell response. It is demonstrated that an adjustable magnetic acoustic metamaterial can be fabricated at ultra-subwavelength dimensions ( /77.5), exhibiting adjustable resonance from 88.73 to 86.63 Hz. It is anticipated that this research will drive new innovations in adjustable metamaterials, including wider frequency ranges.
PubMed: 38951634
DOI: 10.1038/s41598-024-65819-2 -
Communications Biology Jun 2024According to single-molecule localisation microscopy almost all plasma membrane proteins are clustered. We demonstrate that clusters can arise from variations in...
According to single-molecule localisation microscopy almost all plasma membrane proteins are clustered. We demonstrate that clusters can arise from variations in membrane topography where the local density of a randomly distributed membrane molecule to a degree matches the variations in the local amount of membrane. Further, we demonstrate that this false clustering can be differentiated from genuine clustering by using a membrane marker to report on local variations in the amount of membrane. In dual colour live cell single molecule localisation microscopy using the membrane probe DiI alongside either the transferrin receptor or the GPI-anchored protein CD59, we found that pair correlation analysis reported both proteins and DiI as being clustered, as did its derivative pair correlation-photoactivation localisation microscopy and nearest neighbour analyses. After converting the localisations into images and using the DiI image to factor out topography variations, no CD59 clusters were visible, suggesting that the clustering reported by the other methods is an artefact. However, the TfR clusters persisted after topography variations were factored out. We demonstrate that membrane topography variations can make membrane molecules appear clustered and present a straightforward remedy suitable as the first step in the cluster analysis pipeline.
Topics: Single Molecule Imaging; Cell Membrane; CD59 Antigens; Receptors, Transferrin; Humans; Membrane Proteins; Cluster Analysis; Microscopy, Fluorescence
PubMed: 38951588
DOI: 10.1038/s42003-024-06472-3 -
Scientific Reports Jul 2024In this study, composite electrodes with metal-organic framework (MOF) for brackish water desalination via capacitive deionization (CDI) were developed. The electrodes...
In this study, composite electrodes with metal-organic framework (MOF) for brackish water desalination via capacitive deionization (CDI) were developed. The electrodes contained activated carbon (AC), polyvinylidene fluoride (PVDF), and zinc-benzene tricarboxylic acid (Zn-BTC) MOF in varying proportions, improving their electrochemical performance. Among them, the E4 electrode with 6% Zn-BTC MOF exhibited the best performance in terms of CV and EIS analyses, with a specific capacity of 88 F g and low ion charge transfer resistance of 4.9 Ω. The E4 electrode showed a 46.7% increase in specific capacitance compared to the E1 electrode, which did not include the MOF. Physicochemical analyses, including XRD, FTIR, FESEM, BET, EDS, elemental mapping, and contact angle measurements, verified the superior properties of the E4 electrode compared to E1, showcasing successful MOF synthesis, desirable pore size, elemental and particle-size distribution of materials, and the superior hydrophilicity enhancement. By evaluating salt removal capacity (SRC) in various setups using an initially 100.0 mg L NaCl feed solution, the asymmetric arrangement of E1 and E4 electrodes outperformed symmetric arrangements, achieving a 21.1% increase in SRC to 6.3 mg g. This study demonstrates the potential of MOF-incorporated electrodes for efficient CDI desalination processes.
PubMed: 38951566
DOI: 10.1038/s41598-024-66023-y -
Molecular and Cellular Biochemistry Jun 2024Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid...
Despite the implementation of novel therapeutic regimens and extensive research efforts, chemoresistance remains a formidable challenge in the treatment of acute myeloid leukemia (AML). Notably, the involvement of lysosomes in chemoresistance has sparked interest in developing lysosome-targeted therapies to sensitize tumor cells to currently approved chemotherapy or as innovative pharmacological approaches. Moreover, as ion channels on the lysosomal membrane are critical regulators of lysosomal function, they present potential as novel targets for enhancing chemosensitivity. Here, we discovered that the expression of a lysosomal cation channel, namely transient receptor potential mucolipin 1 (TRPML1), was elevated in AML cells. Inhibiting TRPML1 individually does not impact the proliferation and apoptosis of AML cells. Importantly, inhibition of TRPML1 demonstrated the potential to modulate the sensitivity of AML cells to chemotherapeutic agents. Exploration of the underlying mechanisms revealed that suppression of TRPML1 impaired autophagy while concurrently increasing the production of reactive oxygen species (ROS) and ROS-mediated lipid peroxidation (Lipid-ROS) in AML cells. Finally, the knockdown of TRPML1 significantly reduced OCI-AML3 tumor growth following chemotherapy in a mouse model of human leukemia. In summary, targeting TRPML1 represents a promising approach for combination therapy aimed at enhancing chemosensitivity in treating AML.
PubMed: 38951379
DOI: 10.1007/s11010-024-05054-5 -
Archives of Microbiology Jul 2024Ionic liquids (ILs) are interesting chemical compounds that have a wide range of industrial and scientific applications. They have extraordinary properties, such as the...
Ionic liquids (ILs) are interesting chemical compounds that have a wide range of industrial and scientific applications. They have extraordinary properties, such as the tunability of many of their physical properties and, accordingly, their activities; and the ease of synthesis methods. Hence, they became important building blocks in catalysis, extraction, electrochemistry, analytics, biotechnology, etc. This study determined antifungal activities of various imidazolium-based ionic liquids against yeast Saccharomyces cerevisiae via minimum inhibitory concentration (MIC) estimation method. Increasing the length of the alkyl group attached to the imidazolium cation, enhanced the antifungal activity of the ILs, as well as their ability of the disruption of the cell membrane integrity. FTIR studies performed on the S. cerevisiae cells treated with the ILs revealed alterations in the biochemical composition of these cells. Interestingly, the alterations in fatty acid content occurred in parallel with the increase in the activity of the molecules upon the increase in the length of the attached alkyl group. This trend was confirmed by statistical analysis and machine learning methodology. The classification of antifungal activities based on FTIR spectra of S. cerevisiae cells yielded a prediction accuracy of 83%, indicating the pharmacy and medicine industries could benefit from machine learning methodology. Furthermore, synthesized ionic compounds exhibit significant potential for pharmaceutical and medical applications.
Topics: Saccharomyces cerevisiae; Ionic Liquids; Imidazoles; Antifungal Agents; Cell Membrane; Microbial Sensitivity Tests; Spectroscopy, Fourier Transform Infrared
PubMed: 38951200
DOI: 10.1007/s00203-024-04043-y -
Communications Biology Jul 2024The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace...
The highly complex structure of the brain requires an approach that can unravel its connectivity. Using volume electron microscopy and a dedicated software we can trace and measure all nerve fibers present within different samples of brain tissue. With this software tool, individual dendrites and axons are traced, obtaining a simplified "skeleton" of each fiber, which is linked to its corresponding synaptic contacts. The result is an intricate meshwork of axons and dendrites interconnected by a cloud of synaptic junctions. To test this methodology, we apply it to the stratum radiatum of the hippocampus and layers 1 and 3 of the somatosensory cortex of the mouse. We find that nerve fibers are densely packed in the neuropil, reaching up to 9 kilometers per cubic mm. We obtain the number of synapses, the number and lengths of dendrites and axons, the linear densities of synapses established by dendrites and axons, and their location on dendritic spines and shafts. The quantitative data obtained through this method enable us to identify subtle traits and differences in the synaptic organization of the samples, which might have been overlooked in a qualitative analysis.
Topics: Animals; Mice; Microscopy, Electron; Nerve Fibers; Synapses; Axons; Dendrites; Brain; Somatosensory Cortex; Mice, Inbred C57BL; Male; Software; Hippocampus; Volume Electron Microscopy
PubMed: 38951162
DOI: 10.1038/s42003-024-06491-0