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Communications Biology May 2024Two mammalian homologs of systemic RNA interference defective protein 1 (SID-1) (SIDT1/2) are suggested to function as double-stranded RNA (dsRNA) transporters for...
Two mammalian homologs of systemic RNA interference defective protein 1 (SID-1) (SIDT1/2) are suggested to function as double-stranded RNA (dsRNA) transporters for extracellular dsRNA uptake or for release of incorporated dsRNA from lysosome to cytoplasm. SIDT1/2 is also suggested to be involved in cholesterol transport and lipid metabolism. Here, we determine the cryo-electron microscopy structures of human SIDT1, homodimer in a side-by-side arrangement, with two distinct conformations, the cholesterol-bound form and the unbound form. Our structures reveal that the membrane-spanning region of SIDT1 harbors conserved histidine and aspartate residues coordinating to putative zinc ion, in a structurally similar manner to alkaline ceramidases or adiponectin receptors that require zinc for ceramidase activity. We identify that SIDT1 has a ceramidase activity that is attenuated by cholesterol binding. Observations from two structures suggest that cholesterol molecules serve as allosteric regulator that binds the transmembrane region of SIDT1 and induces the conformation change and the reorientation of the catalytic residues. This study represents a contribution to the elucidation of the cholesterol-mediated mechanisms of lipid hydrolytic activity and RNA transport in the SID-1 family proteins.
Topics: Humans; Cryoelectron Microscopy; Hydrolysis; Cholesterol; Lipid Metabolism; Protein Conformation; Models, Molecular; Protein Binding
PubMed: 38811802
DOI: 10.1038/s42003-024-06346-8 -
RSC Advances May 2024Nanopore technology, re-fueled by two-dimensional (2D) materials such as graphene and MoS, controls mass transport by allowing certain species while denying others at...
Nanopore technology, re-fueled by two-dimensional (2D) materials such as graphene and MoS, controls mass transport by allowing certain species while denying others at the nanoscale and has a wide application range in DNA sequencing, nano-power generation, and others. With their low transmembrane transport resistance and high permeability stemming from their ultrathin nature, crystalline 2D materials do not possess nanoscale holes naturally, thus requiring additional fabrication to create nanopores. Herein, we demonstrate that nanopores exist in amorphous monolayer carbon (AMC) grown at low temperatures. The size and density of nanopores can be tuned by the growth temperature, which was experimentally verified by atomic images and further corroborated by kinetic Monte Carlo simulation. Furthermore, AMC films with varied degrees of disorder (DOD) exhibit tunable transmembrane ionic conductance over two orders of magnitude when serving as nanopore membranes. This work demonstrates the DOD-tuned property in amorphous monolayer carbon and provides a new candidate for modern membrane science and technology.
PubMed: 38808236
DOI: 10.1039/d4ra01523a -
Frontiers in Cell and Developmental... 2024The biophysics of water, has been debated over more than a century. Although its importance is still underestimated, significant breakthroughs occurred in recent years....
The biophysics of water, has been debated over more than a century. Although its importance is still underestimated, significant breakthroughs occurred in recent years. The influence of protein condensation on water availability control was documented, new findings on water-transport proteins emerged, and the way water molecules rearrange to minimize free energy at interfaces was deciphered, influencing membrane thermodynamics. The state of knowledge continued to progress in the field of deep-sea marine biology, highlighting unknown effects of high hydrostatic pressure and/or temperature on interactions between proteins and ligands in extreme environments, and membrane structure adaptations. The role of osmolytes in protein stability control under stress is also discussed here in relation to fish egg hydration/buoyancy. The complexity of water movements within the cell is updated, all these findings leading to a better view of their impact on many cellular processes. The way water flow and osmotic gradients generated by ion transport work together to produce the driving force behind cell migration is also relevant to both marine biology and cancer research. Additional common points concern water dynamic changes during the neoplastic transformation of cells and tissues, or embryo development. This could improve imaging techniques, early cancer diagnosis, and understanding of the molecular and physiological basis of buoyancy for many marine species.
PubMed: 38803391
DOI: 10.3389/fcell.2024.1403037 -
Nature Communications May 2024The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive...
The emergence of glioblastoma in cortical tissue initiates early and persistent neural hyperexcitability with signs ranging from mild cognitive impairment to convulsive seizures. The influence of peritumoral synaptic density, expansion dynamics, and spatial contours of excess glutamate upon higher order neuronal network modularity is unknown. We combined cellular and widefield imaging of calcium and glutamate fluorescent reporters in two glioblastoma mouse models with distinct synaptic microenvironments and infiltration profiles. Functional metrics of neural ensembles are dysregulated during tumor invasion depending on the stage of malignant progression and tumor cell proximity. Neural activity is differentially modulated during periods of accelerated and inhibited tumor expansion. Abnormal glutamate accumulation precedes and outpaces the spatial extent of baseline neuronal calcium signaling, indicating these processes are uncoupled in tumor cortex. Distinctive excitability homeostasis patterns and functional connectivity of local and remote neuronal populations support the promise of precision genetic diagnosis and management of this devastating brain disease.
Topics: Glioblastoma; Animals; Brain Neoplasms; Mice; Humans; Nerve Net; Glutamic Acid; Neurons; Cerebral Cortex; Calcium Signaling; Disease Models, Animal; Male; Calcium; Female
PubMed: 38802334
DOI: 10.1038/s41467-024-48757-5 -
Nature Communications May 2024Solid-state lithium-based batteries offer higher energy density than their Li-ion counterparts. Yet they are limited in terms of negative electrode discharge performance...
Solid-state lithium-based batteries offer higher energy density than their Li-ion counterparts. Yet they are limited in terms of negative electrode discharge performance and require high stack pressure during operation. To circumvent these issues, we propose the use of lithium-rich magnesium alloys as suitable negative electrodes in combination with LiPSCl solid-state electrolyte. We synthesise and characterise lithium-rich magnesium alloys, quantifying the changes in mechanical properties, transport, and surface chemistry that impact electrochemical performance. Increases in hardness, stiffness, adhesion, and resistance to creep are quantified by nanoindentation as a function of magnesium content. A decrease in diffusivity is quantified with Li pulsed field gradient nuclear magnetic resonance, and only a small increase in interfacial impedance due to the presence of magnesium is identified by electrochemical impedance spectroscopy which is correlated with x-ray photoelectron spectroscopy. The addition of magnesium aids contact retention on discharge, but this must be balanced against a decrease in lithium diffusivity. We demonstrate via electrochemical testing of symmetric cells at 2.5 MPa and 30C that 1% magnesium content in the alloy increases the stripping capacity compared to both pure lithium and higher magnesium content alloys by balancing these effects.
PubMed: 38802332
DOI: 10.1038/s41467-024-48071-0 -
Revista Medica de Chile Jun 2023Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium... (Review)
Review
Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.
Topics: Humans; Hypertension, Pulmonary; Calcium Channels; Animals; Calcium Signaling; Calcium Channel Blockers; Signal Transduction; Pulmonary Artery; Vasoconstriction
PubMed: 38801384
DOI: 10.4067/s0034-98872023000600753 -
ACS Omega May 2024This study presents the in situ synthesis of CNT@SrTiO nanocomposite films for the development of high-performance flexible supercapacitors. The synthesis process...
This study presents the in situ synthesis of CNT@SrTiO nanocomposite films for the development of high-performance flexible supercapacitors. The synthesis process involved the use of organic-inorganic hybrid polymers containing metal elements as precursors for thermal decomposition reaction under a reducing atmosphere. Due to the formation of chemical bonding between Ti elements and the CNTs, the interface between STO and CNT surface could provide additional active sites for ion transport and storage. Thereby, the incorporation of SrTiO nanoparticles into CNTs enhanced the electrochemical performance of the resulting nanocomposite membranes. To further investigate the influence of STO content and synthesis temperature, we conducted a detailed analysis. The findings indicated that the CNT@STO film with 25% STO content, synthesized at 700 °C, and possessed optimal performance with an areal capacitance of 6682 mF·cm at 5 mV·s. Furthermore, a symmetrical flexible supercapacitor assembled by two CNT@STO-25 electrodes demonstrated strong application potential in wearable devices, owing to its long cycle life, excellent flexibility, and high energy density of 430.2 μWh·cm (corresponding power density of 4.5 mW·cm). Based on these results, we believe that this study provides a fresh idea for the development of novel flexible energy storage materials.
PubMed: 38799353
DOI: 10.1021/acsomega.4c01890 -
ACS Omega May 20242D material-based membranes have emerged as promising candidates for next-generation separation technology due to their exceptional permeability and selectivity....
2D material-based membranes have emerged as promising candidates for next-generation separation technology due to their exceptional permeability and selectivity. Integration of these membranes into microfluidic devices has offered significant potential for improving the efficiency, throughput, and precision. However, designing compact and reliable microfluidic devices with membranes has many challenges, including complexities in membrane integration, analyte measurement, and contamination issues. Addressing these challenges is critical for unlocking the full potential of membrane-integrated devices. This paper proposes a systematic procedure for integrating membranes into a microfluidic device by creating a pore in the middle layer. Furthermore, an ion transport experiment is carried out across various stacked graphene and poly carbonate track etch membranes in an Ostemer-based device. The resulting device is capable of facilitating the concurrent measurement, a task that is cumbersome in standard macroscopic diffusion cells. The transparency and compactness of the microfluidic device allowed for the in situ and real-time optical characterization of analytes. The integration of microfluidic devices with 2D nanoporous membranes has enabled the incorporation of several analytical modalities, resulting in a highly versatile platform with numerous applications.
PubMed: 38799317
DOI: 10.1021/acsomega.4c01688 -
The Plant Genome May 2024Nitrogen (N) as an inorganic macronutrient is inevitable for plant growth, development, and biomass production. Many external factors and stresses, such as acidity,... (Review)
Review
Nitrogen (N) as an inorganic macronutrient is inevitable for plant growth, development, and biomass production. Many external factors and stresses, such as acidity, alkalinity, salinity, temperature, oxygen, and rainfall, affect N uptake and metabolism in plants. The uptake of ammonium (NH ) and nitrate (NO ) in plants mainly depends on soil properties. Under the sufficient availability of NO (>1 mM), low-affinity transport system is activated by gene network NRT1, and under low NO availability (<1 mM), high-affinity transport system starts functioning encoded by NRT2 family of genes. Further, under limited N supply due to edaphic and climatic factors, higher expression of the AtNRT2.4 and AtNRT2.5T genes of the NRT2 family occur and are considered as N remobilizing genes. The NH ion is the final form of N assimilated by cells mediated through the key enzymes glutamine synthetase and glutamate synthase. The WRKY1 is a major transcription factor of the N regulation network in plants. However, the transcriptome and metabolite profiles show variations in N assimilation metabolites, including glycine, glutamine, and aspartate, under abiotic stresses. The overexpression of NO transporters (OsNRT2.3a and OsNRT1.1b) can significantly improve the biomass and yield of various crops. Altering the expression levels of genes could be a valuable tool to improve N metabolism under the challenging conditions of soil and environment, such as unfavorable temperature, drought, salinity, heavy metals, and nutrient stress.
PubMed: 38797919
DOI: 10.1002/tpg2.20461 -
Asia Pacific Journal of Clinical... Jun 2024This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese...
BACKGROUND AND OBJECTIVES
This study aimed to assess the associations of maternal iron status and placental iron transport proteins expression with the risk of pre-eclampsia (PE) in Chinese pregnant women.
METHODS AND STUDY DESIGN
A total of 94 subjects with PE and 112 healthy pregnant women were enrolled. Fasting blood samples were collected to detect maternal iron status. The placenta samples were collected at delivery to detect the mRNA and protein expression of divalent metal transporter 1 (DMT1) and ferroportin-1 (FPN1). Logistic analysis was used to explore the associations of maternal iron status with PE risk. The associations of placental iron transport proteins with maternal iron status were explored.
RESULTS
After adjusting for covariates, dietary total iron, non-heme iron intake and serum hepcidin were negatively associated with PE, with adjusted ORs (95%CIs) were 0.40 (0.17, 0.91), 0.42 (0.18, 0.94) and 0.02 (0.002, 0.13) for the highest versus lowest tertile, respectively. For the highest tertile versus lowest tertile, serum iron (4.08 (1.58, 10.57)) and ferritin (5.61 (2.36, 13.31)) were positively associated with PE. The mRNA expressions and protein levels of DMT1 and FPN1 in placenta were up-regulated in the PE group (p < 0.05). The mRNA expressions of DMT1 and FPN1 in placenta showed a negative correlation with the serum hepcidin (r = -0.71, p < 0.001; r = -0.49, p < 0.05).
CONCLUSIONS
In conclusion, the maternal iron status were closely associated with PE risk, placental DMT1 and FPN1 were upregulated in PE which may be a promising target for the prevention of PE.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Case-Control Studies; Adult; Iron; Placenta; Cation Transport Proteins; Hepcidins; Risk Factors; China; Nutritional Status
PubMed: 38794978
DOI: 10.6133/apjcn.202406_33(2).0005