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Fly Dec 2024Adenosine-to-inosine (A-to-I) RNA editing recodes the genome and confers flexibility for the organisms to adapt to the environment. It is believed that RNA recoding...
Adenosine-to-inosine (A-to-I) RNA editing recodes the genome and confers flexibility for the organisms to adapt to the environment. It is believed that RNA recoding sites are well suited for facilitating adaptive evolution by increasing the proteomic diversity in a temporal-spatial manner. The function and essentiality of a few conserved recoding sites are recognized. However, the experimentally discovered functional sites only make up a small corner of the total sites, and there is still the need to expand the repertoire of such functional sites with bioinformatic approaches. In this study, we define a new category of RNA editing sites termed 'conserved editing with non-conserved recoding' and systematically identify such sites in editomes, figuring out their selection pressure and signals of adaptation at inter-species and intra-species levels. Surprisingly, conserved editing sites with non-conserved recoding are not suppressed and are even slightly overrepresented in . DNA mutations leading to such cases are also favoured during evolution, suggesting that the function of those recoding events in different species might be diverged, specialized, and maintained. Finally, structural prediction suggests that such recoding in potassium channel Shab might increase ion permeability and compensate the effect of low temperature. In conclusion, conserved editing with non-conserved recoding might be functional as well. Our study provides novel aspects in considering the adaptive evolution of RNA editing sites and meanwhile expands the candidates of functional recoding sites for future validation.
Topics: Animals; RNA Editing; Inosine; Drosophila; Adenosine; Drosophila melanogaster; Evolution, Molecular; Drosophila Proteins
PubMed: 38889318
DOI: 10.1080/19336934.2024.2367359 -
PloS One 2024The purpose of this work was to investigate the degree of agreement between two distinct approaches for measuring a set of blood values and to compare comfort levels...
The purpose of this work was to investigate the degree of agreement between two distinct approaches for measuring a set of blood values and to compare comfort levels reported by participants when utilizing these two disparate measurement methods. Radial arterial blood was collected for the comparator analysis using the Abbott i-STAT® POCT device. In contrast, the non-invasive proprietary DBC methodology is used to calculate sodium, potassium, chloride, ionized calcium, total carbon dioxide, pH, bicarbonate, and oxygen saturation using four input parameters (temperature, hemoglobin, pO2, and pCO2). Agreement between the measurement for a set of blood values obtained using i-STAT and DBC methodology was compared using intraclass correlation coefficients, Passing and Bablok regression analyses, and Bland Altman plots. A p-value of <0.05 was considered statistically significant. A total of 37 participants were included in this study. The mean age of the participants was 42.4 ± 13 years, most were male (65%), predominantly Caucasian/White (75%), and of Hispanic ethnicity (40%). The Intraclass Correlation Coefficients (ICC) analyses indicated agreement levels ranging from poor to moderate between i-STAT and the DBC's algorithm for Hb, pCO2, HCO3, TCO2, and Na, and weak agreement for pO2, HSO2, pH, K, Ca, and Cl. The Passing and Bablok regression analyses demonstrated that values for Hb, pO2, pCO2, TCO2, Cl, and Na obtained from the i-STAT did not differ significantly from that of the DBC's algorithm suggesting good agreement. The values for Hb, K, and Na measured by the DBC algorithm were slightly higher than those obtained by the i-STAT, indicating some systematic differences between these two methods on Bland Altman Plots. The non-invasive DBC methodology was found to be reliable and robust for most of the measured blood values compared to invasive POCT i-STAT device in healthy participants. These findings need further validation in larger samples and among individuals afflicted with various medical conditions.
Topics: Humans; Male; Female; Adult; Point-of-Care Systems; Middle Aged; Blood Gas Analysis; Oxygen; Bicarbonates; Hydrogen-Ion Concentration; Hemoglobins; Algorithms; Carbon Dioxide
PubMed: 38889168
DOI: 10.1371/journal.pone.0304706 -
Scientific Reports Jun 2024Iron in the leaching solution with high K and Na concentrations was usually precipitated as the typical hazardous and toxic jarosite residues. However, this method of...
Iron in the leaching solution with high K and Na concentrations was usually precipitated as the typical hazardous and toxic jarosite residues. However, this method of treatment has been greatly restricted by increasingly strict environmental regulations. Here we propose that iron can be precipitated from the solution with high K and Na concentrations as recyclable hematite products by adjusting the concentration ratio of sodium and potassium ions in the solution. The transformation behavior of jarosite into hematite in high concentration potassium ion and sodium ion solution was explained based on collision theory. The results indicated that in instances where the concentration ratio of Na/K is ≥ 4:1, the iron present in the solution can be effectively precipitated as a recyclable hematite product, as opposed to forming the conventional hazardous jarosite residue, even under conditions where the potassium ion concentration reaches levels as high as 4 g/L. On the other hand, thermodynamic and molecular dynamics simulations indicate that at a temperature of 185 °C, the decomposition transformation of Na-jarosite (32.64 kJ and 7.25 eV) is more energetically advantageous compared to that of K-jarosite (61.07 kJ and 15.31 eV). The results were verified by the leaching solution from smelting industry. The iron content in the residues is above 58%, the sulfur content is below 4%, the zinc content is below 1%, and the total iron concentration in the supernatant is about 4 g/L, reaching the production index of the smelting industry. The green, environmentally friendly, and recyclable separation of iron in a solution with high concentrations of potassium and sodium ions is achieved, which is of great significance for the treatment of iron-containing solution and wastewater in the chemical industry and metallurgy fields.
PubMed: 38886494
DOI: 10.1038/s41598-024-64502-w -
Nature Communications Jun 2024The renal epithelium is sensitive to changes in blood potassium (K). We identify the basolateral K channel, Kir4.2, as a mediator of the proximal tubule response to K...
The renal epithelium is sensitive to changes in blood potassium (K). We identify the basolateral K channel, Kir4.2, as a mediator of the proximal tubule response to K deficiency. Mice lacking Kir4.2 have a compensated baseline phenotype whereby they increase their distal transport burden to maintain homeostasis. Upon dietary K depletion, knockout animals decompensate as evidenced by increased urinary K excretion and development of a proximal renal tubular acidosis. Potassium wasting is not proximal in origin but is caused by higher ENaC activity and depends upon increased distal sodium delivery. Three-dimensional imaging reveals Kir4.2 knockouts fail to undergo proximal tubule expansion, while the distal convoluted tubule response is exaggerated. AKT signaling mediates the dietary K response, which is blunted in Kir4.2 knockouts. Lastly, we demonstrate in isolated tubules that AKT phosphorylation in response to low K depends upon mTORC2 activation by secondary changes in Cl transport. Data support a proximal role for cell Cl which, as it does along the distal nephron, responds to K changes to activate kinase signaling.
Topics: Animals; Proto-Oncogene Proteins c-akt; Potassium Channels, Inwardly Rectifying; TOR Serine-Threonine Kinases; Signal Transduction; Mice, Knockout; Potassium; Kidney Tubules, Proximal; Mice; Mechanistic Target of Rapamycin Complex 2; Phosphorylation; Male; Chlorides; Mice, Inbred C57BL
PubMed: 38886379
DOI: 10.1038/s41467-024-49562-w -
ENeuro Jun 2024Persistent activity in excitatory pyramidal cells is a putative mechanism for maintaining memory traces during working memory. We recently demonstrated persistent...
Persistent activity in excitatory pyramidal cells is a putative mechanism for maintaining memory traces during working memory. We recently demonstrated persistent interruption of firing in fast-spiking parvalbumin-expressing interneurons (PV-INs), a phenomenon which could serve as a substrate for persistent activity in pyramidal cells through disinhibition lasting hundreds of milliseconds. Here, we find that hippocampal CA1 PV-INs exhibit type 2 excitability, like striatal and neocortical PV-INs. Modelling and mathematical analysis showed that the slowly inactivating potassium current K1 contributes to type 2 excitability, enables the multiple firing regimes observed experimentally in PV-INs, and provides a mechanism for robust persistent interruption of firing. Using a fast/slow separation of times scales approach with the K1 inactivation variable as a bifurcation parameter shows that the initial inhibitory stimulus stops repetitive firing by moving the membrane potential trajectory onto a co-existing stable fixed point corresponding to a non-spiking quiescent state. As K1 inactivation decays, the trajectory follows the branch of stable fixed points until it crosses a subcritical Hopf bifurcation then spirals out into repetitive firing. In a model describing entorhinal cortical PV-INs without K1, interruption of firing could be achieved by taking advantage of the bistability inherent in type 2 excitability based on a subcritical Hopf bifurcation, but the interruption was not robust to noise. Persistent interruption of firing is therefore broadly applicable to PV-INs in different brain regions but is only made robust to noise in the presence of a slow variable, K1 inactivation. Persistent activity in neuronal networks is thought to provide a substrate for multiple forms of memory. The architecture of neuronal networks across many brain regions involves a small number of locally-projecting inhibitory neurons that control many excitatory pyramidal neurons which provide the output of the region. We propose that persistent silencing of fast-spiking parvalbumin-expressing inhibitory interneurons (PV-INs) can result in persistent activity of pyramidal neurons. We use a mathematical approach and computer simulations to show how a slowly changing state of a particular ion channel controls the long-lasting silence imposed by persistent interruption. Overall, our results provide a conceptual framework that positions the persistent interruption of PV-INs firing as a potential mechanism for persistent activity in pyramidal cells.
PubMed: 38886063
DOI: 10.1523/ENEURO.0190-24.2024 -
ACS Omega Jun 2024Transition-metal dichalcogenides (TMDs) and their alloys are vital for the development of sustainable and economical energy storage alternatives due to their large...
Transition-metal dichalcogenides (TMDs) and their alloys are vital for the development of sustainable and economical energy storage alternatives due to their large interlayer spacing and hosting ability for alkali-metal ions. Although the Li-ion chemically correlates with the Na-ion and K-ion, research on batteries with TMD anodes for K is still in its infancy. This research explores TMDs such as molybdenum disulfide (MoS) and tungsten disulfide (WS) and TMD alloys such as molybdenum tungsten disulfide (MoWS) for both sodium-ion batteries (NIBs) and potassium-ion batteries (KIBs). The cyclic stability test analysis indicates that in the initial cycle, the MoS NIB demonstrates exceptional performance, with a peak charge capacity of 1056 mAh g, while retaining high Coulombic efficiency. However, the WS KIB underperforms, with the least charge capacity of 130 mAh g in the first cycle and exceptionally low retention at a current density of 100 mA g. The MoWS TMD alloy exhibits a moderate charge capacity and cyclic efficiency for both NIBs and KIBs. This comparison study shows that decreasing sizes of alkali-metal ions and constituent elements in TMDs or TMD alloys leads to decreased resistance and slower degradation processes as indicated by cyclic voltammetry and electrochemical impedance spectroscopy after 10 cycles. Furthermore, the study of probable electrochemical intercalation and removal processes of Na-ions and K-ions demonstrates that large geometrically shaped TMD flakes are more responsive to intercalation for Na-ions than K-ions. These performance comparisons of different TMD materials for NIBs and KIBs may promote the future development of these batteries.
PubMed: 38882118
DOI: 10.1021/acsomega.4c01966 -
Ecotoxicology and Environmental Safety Jul 2024The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have...
The combined cadmium (Cd) and acid rain pollution poses a significant threat to the global ecological environment. Previous studies on the combined adverse effects have predominantly focused on the aboveground plant physiological responses, with limited reports on the microbial response in the rhizosphere soil. This study employed Populus beijingensis seedlings and potting experiments to simulate the impacts of combined mild acid rain (pH=4.5, MA) or highly strong acid rain (pH=3.0, HA), and soil Cd pollution on the composition and diversity of microbial communities, as well as the physiochemical properties in the rhizosphere soil. The results showed that Cd decreased the content of inorganic nitrogen, resulting in an overall decrease of 49.10 % and 46.67 % in ammonium nitrogen and nitrate nitrogen, respectively. Conversely, acid rain was found to elevate the content of total potassium and soil organic carbon by 4.68 %-6.18 % and 8.64-19.16 %, respectively. Additionally, simulated acid rain was observed to decrease the pH level by 0.29-0.35, while Cd increased the pH level by 0.11. Moreover, Cd alone reduced the rhizosphere bacterial diversity, however, when combined with acid rain, regardless of its intensity, Cd was observed to increase the diversity. Fungal diversity was not influenced by the acid rain, but Cd increased fungal diversity to some extend under HA as observed in bacterial diversity. In addition, composition of the rhizosphere bacterial community was primarily influenced by the inorganic nitrogen components, while the fungal community was driven mainly by soil pH. Furthermore, "Metabolism" was emerged as the most significant bacterial function, which was markedly affected by the combined pollution, while Cd pollution led to a shift from symbiotroph to other trophic types for fungi. These findings suggest that simulated acid rain has a mitigating effect on the diversity of rhizosphere bacteria affected by Cd pollution, and also alters the trophic type of these microorganisms. This can be attributed to the acid rain-induced direct acidic environment, as well as the indirect changes in the availability or sources of carbon, nitrogen, or potassium.
Topics: Cadmium; Soil Microbiology; Populus; Acid Rain; Soil Pollutants; Seedlings; Rhizosphere; Nitrogen; Soil; Microbiota; Hydrogen-Ion Concentration; Bacteria; Fungi
PubMed: 38878333
DOI: 10.1016/j.ecoenv.2024.116583 -
Scientific Reports Jun 2024Neuronal activity is accompanied by a net outflow of potassium ions (K) from the intra- to the extracellular space. While extracellular [K] changes during neuronal...
Neuronal activity is accompanied by a net outflow of potassium ions (K) from the intra- to the extracellular space. While extracellular [K] changes during neuronal activity are well characterized, intracellular dynamics have been less well investigated due to lack of respective probes. In the current study we characterized the FRET-based K biosensor lc-LysM GEPII 1.0 for its capacity to measure intracellular [K] changes in primary cultured neurons and in mouse cortical neurons in vivo. We found that lc-LysM GEPII 1.0 can resolve neuronal [K] decreases in vitro during seizure-like and intense optogenetically evoked activity. [K] changes during single action potentials could not be recorded. We confirmed these findings in vivo by expressing lc-LysM GEPII 1.0 in mouse cortical neurons and performing 2-photon fluorescence lifetime imaging. We observed an increase in the fluorescence lifetime of lc-LysM GEPII 1.0 during periinfarct depolarizations, which indicates a decrease in intracellular neuronal [K]. Our findings suggest that lc-LysM GEPII 1.0 can be used to measure large changes in [K] in neurons in vitro and in vivo but requires optimization to resolve smaller changes as observed during single action potentials.
Topics: Animals; Potassium; Neurons; Mice; Biosensing Techniques; Action Potentials; Cells, Cultured; Fluorescence Resonance Energy Transfer; Optogenetics
PubMed: 38877089
DOI: 10.1038/s41598-024-62993-1 -
The Journal of Biological Chemistry Jun 2024The voltage-gated potassium ion channel K11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause Long QT Syndrome...
The voltage-gated potassium ion channel K11.1 plays a critical role in cardiac repolarization. Genetic variants that render Kv11.1 dysfunctional cause Long QT Syndrome (LQTS), which is associated with fatal arrhythmias. Approximately 90% of LQTS-associated variants cause intracellular protein transport (trafficking) dysfunction, which pharmacological chaperones like E-4031 can rescue. Protein folding and trafficking decisions are regulated by chaperones, protein quality control factors, and trafficking machinery comprising the cellular proteostasis network. Here, we test whether trafficking dysfunction is associated with alterations in the proteostasis network of pathogenic Kv11.1 variants and whether pharmacological chaperones can normalize the proteostasis network of responsive variants. We used affinity-purification coupled with tandem mass tag-based quantitative mass spectrometry to assess protein interaction changes of wild-type (WT) K11.1 or trafficking-deficient channel variants in the presence or absence of E4031. We identified 572 core K11.1 protein interactors. Trafficking-deficient variants K11.1-G601S and K11.1-G601S-G965* had significantly increased interactions with proteins responsible for folding, trafficking, and degradation compared to WT. We confirmed previous findings that the proteasome is critical for K11.1 degradation. Our report provides the first comprehensive characterization of protein quality control mechanisms of K11.1. We find extensive interactome remodeling associated with trafficking-deficient K11.1 variants, and with pharmacological chaperone rescue of K11.1 cell surface expression. The identified protein interactions could be targeted therapeutically to improve K11.1 trafficking and treat Long QT Syndrome.
PubMed: 38876300
DOI: 10.1016/j.jbc.2024.107465 -
MBio Jun 2024Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the family of the order. LCMV is associated with...
Lymphocytic choriomeningitis virus (LCMV) is an enveloped and segmented negative-sense RNA virus classified within the family of the order. LCMV is associated with fatal disease in immunocompromised populations and, as the prototypical arenavirus member, acts as a model for the many highly pathogenic members of the family, such as Junín, Lassa, and Lujo viruses, all of which are associated with devastating hemorrhagic fevers. To enter cells, the LCMV envelope fuses with late endosomal membranes, for which two established requirements are low pH and interaction between the LCMV glycoprotein (GP) spike and secondary receptor CD164. LCMV subsequently uncoats, where the RNA genome-associated nucleoprotein (NP) separates from the Z protein matrix layer, releasing the viral genome into the cytosol. To further examine LCMV endosome escape, we performed an siRNA screen which identified host cell potassium ion (K) channels as important for LCMV infection, with pharmacological inhibition confirming K channel involvement during the LCMV entry phase completely abrogating productive infection. To better understand the K-mediated block in infection, we tracked incoming virions along their entry pathway under physiological conditions, where uncoating was signified by separation of NP and Z proteins. In contrast, K channel blockade prevented uncoating, trapping virions within Rab7 and CD164-positive endosomes, identifying K as a third LCMV entry requirement. K did not increase GP-CD164 binding or alter GP-CD164-dependent fusion. Thus, we propose that K mediates uncoating by modulating NP-Z interactions within the virion interior. These results suggest K channels represent a potential anti-arenaviral target.IMPORTANCEArenaviruses can cause fatal human disease for which approved preventative or therapeutic options are not available. Here, using the prototypical LCMV, we identified K channels as critical for arenavirus infection, playing a vital role during the entry phase of the infection cycle. We showed that blocking K channel function resulted in entrapment of LCMV particles within late endosomal compartments, thus preventing productive replication. Our data suggest K is required for LCMV uncoating and genome release by modulating interactions between the viral nucleoprotein and the matrix protein layer inside the virus particle.
PubMed: 38874413
DOI: 10.1128/mbio.01684-23