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Monovalent cation perm-selective membrane (MCPMs) allow fast and selective transport of monovalent cations, and they are promisingly required for extraction of special ions, such as lithium extraction, acid recovery and sea salt production. Herein, we report a novel strategy to design the critical functional layers of MCPMs with both space charge repulsion and cross-linked dense screenability. The in-situ deposition polymerization of pyrrole was carried out on the surface of sulfonated polyphenyl sulfone (SPPSU) substrate membrane followed by cross-linking quaternization of the polypyrrole (PPy) layer with diiodinated functional molecules, thus, the membrane obtained more excellent selective permeability and stable transport properties of monovalent cations. It confirms that the designed PPy layers with charged surface and cross-linking structure improved the hydrophilicity, facilitated cation transport and increased ion flux. Meanwhile, for the dense PPy layer, the charged cross-linked structure endowed the functional layer with the synergistic characteristics of Donnan exclusion and pore size sieving for positively charged ions, which improved the monovalent cation perm-selectivity of the membranes. At a constant current density of 5.1 mA/cm2, the optimal membrane exhibited superior perm-selectivity ( P Mg Na = 2.07 ) and monovalent cation flux (JNa+ = 2.80 × 10 −8 (mol cm−2 s−1)) during electrodialysis.

A number of artificial cation ionophores (or transporters) have been developed for basic research and biomedical applications. However, their mechanisms of action and the putative correlations between changes in intracellular cation concentrations and induced cell death remain poorly understood. Here we show that three hemispherand-strapped calix[4]pyrrole based ion pair receptors act as efficient Na+/K+ exchangers in the presence of Cl- in liposomal models, and promote Na+ influx and K+ efflux (Na+/K+ exchange) in cancer cells to induce apoptosis. Mechanistic studies reveal that these cation exchangers induce endoplasmic reticulum (ER) stress in cancer cells by perturbing intracellular cation homeostasis, promote generation of reactive oxygen species, and eventually enhance mitochondria-mediated apoptosis. However, they neither induce osmotic stress nor affect autophagy. The present study provides support for the notion that synthetic receptors which perturb cellular cation homeostasis may provide a new approach to generating agents with potentially useful apoptotic activity.

We report a single-phase Na4Mn4Ti5O18 oxide prepared via ceramic processing route. Rietveld refinement of X-ray diffraction results indicated orthorhombic unit cell indexed with Pbam space group. Further, structural analysis using X-ray diffraction, transmission electron microscopy and Raman spectroscopy suggested crystal structure comprising two distinct tunnel pathway, polygonal and Z-shaped tunnels with void dimensions ~ 4.07 A and ~ 3.01 A, respectively, suitable for reversible cation transport desirable for energy storage applications. X-ray photoelectron spectroscopy confirmed presence of Mn2+, Mn3+, Mn4+ and Ti4+ in Na4Mn4Ti5O18. Surface morphology in field emission scanning electron microscopy exhibited inhomogenously distributed micro-bead grains separated by well-defined boundaries in good agreement with complex impedance spectrum results. Estimated dc conductivity and surface area is ~ 1.745 × 10− 6 S cm− 1 and ~ 0.66 m2g− 1 respectively. Electrochemical energy storage performance with cell; Na || 1 M NaFSI (EC : DMC, 1:1 v/v%) || Na4Mn4Ti5O18 in voltage range 2.0–3.8 V indicated reversible redox action. Identical cell in voltage range 0.01–2.5 V, exhibited pseudo-capacitive behaviour. Results suggest energy storage possibility with Na4Mn4Ti5O18 electrode.

Despite the progress in modeling complex molecular systems of ever-increasing complexity, a quantitatively accurate computational treatment of ion permeation through narrow membrane channels remains challenging. An important factor to reach this goal is induced electronic polarization, which is likely to impact the permeation rate of small ions through narrow molecular pores. In this work, we extended the recently developed polarizable force field based on the classical Drude oscillators to assess the role of induced polarization effects on the energetics of sodium and potassium ion transport across the gramicidin A (gA) ion channel. The inclusion of induced polarization lowers barriers present in 1D potential of mean force (PMF) for cation permeation by ∼50% compared to those obtained with the additive force field. Conductance properties calculated with 1D PMFs from Drude simulations are in better agreement with experimental results. Polarization of single-file water molecules and protein atoms forming the narrow pore has a direct impact on the free-energy barriers and cation-specific solid-state NMR chemical shifts. Sensitivity analysis indicates that small changes to water–channel interactions can alter the free energy barrier for ion permeation. These results, illustrating polarization effects present in the complex electrostatic environment of the gA channel, have broad implications for revising proposed mechanisms of ion permeation and selectivity in a variety of ion channels.

Recovery and transport of thorium(IV) from HNO3 medium using a polymer inclusion membrane (PIM) containing di (2-ethylhexyl) phosphoric acid (D2EHPA) as the carrier, and polyvinyl chloride (PVC) as polymer were studied. Taguchi L-16 orthogonal array was used to evaluate the effects of the membrane’s carrier content, pH, strip phase type and concentration, and initial concentration of Th(IV) on the cation transport. Using a 45% (m/m) D2EHPA-55% (m/m) PVC PIM, Th(IV) is completely separated from a number of common metal cations. Studies on the transport kinetics and the stability of the membranes were also performed. The results showed that the PIM has excellent stability.

The rechargeable aqueous Zn battery is promising for next-generation wearable energy storage devices, due to its outstanding safety and low cost. Herein, we report a high-performance dual-ion Zn battery with both cations and anions hosted in the polyaniline (PANI) cathode. Of special interest is that a polyzwitterionic hydrogel electrolyte is specifically designed to regulate both the anion and cation transport, which originates from the strong electrostatic interaction between polyzwitterions with counter free ions. The ion-conducting and mechanical properties are then optimized by adjusting the polyzwitterionic content in the hydrogel networks. The intrinsic regulated anion/cation transport channels result in stable and uniform plating/stripping behaviors of the Zn metal anode, and meanwhile promote the cation/anion hosting reaction in the PANI cathode. These synergistic effects provide the Zn/PANI battery with excellent electrochemical performances, achieving a capacity of 102.5 mA h g−1 and a high retention rate of 87.5% after 600 cycles at 5 A g−1. Furthermore, a solid-state pouch cell is prepared for wearable devices with demonstrated excellent electrochemical performances, high flexibility and safety.

Controlling ion transport in nanofluidics is fundamental to water purification, bio-sensing, energy storage, energy conversion, and numerous other applications. For any of these, it is essential to design nanofluidic channels that are stable in the liquid phase and enable specific ions to pass. A human neuron is one such system, where electrical signals are transmitted by cation transport for high-speed communication related to neuromorphic computing. Here, we present a concept of neuro-inspired energy harvesting that uses confined van der Waals crystal and demonstrate a method to maximise the ion diffusion flux to generate an electromotive force. The confined nanochannel is robust in liquids as in neuron cells, enabling steady-state ion diffusion for hundred of hours and exhibiting ion selectivity of 95.8%, energy conversion efficiency of 41.4%, and power density of 5.26 W/m2. This fundamental understanding and rational design strategy can enable previously unrealisable applications of passive-type large-scale power generation., Controlling ion transport in nanofluidics is fundamental to numerous material applications but designing a material for ion selection is challenging. Here the authors report a confined van der Waals graphene oxide membrane as cation selective channel for energy generation inspired by neuron electromotive force.

Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain (TMD), in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal, or multiple metals, from the cytoplasm, and it is not known if the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.

Summary Salt stress has detrimental effects on crop growth and yield, and the area of salt‐affected land is increasing. Soybean is a major source of vegetable protein, oil and feed, but considered as a salt‐sensitive crop. Cultivated soybean (Glycine max) is domesticated from wild soybean (G. soja) but lost considerable amount of genetic diversity during the artificial selection. Therefore, it is important to exploit the gene pool of wild soybean. In this study, we identified 34 salt‐tolerant accessions from wild soybean germplasm and found that a 7‐bp insertion/deletion (InDel) in the promoter of GsERD15B (early responsive to dehydration 15B) significantly affects the salt tolerance of soybean. GsERD15B encodes a protein with transcriptional activation function and contains a PAM2 domain to mediate its interaction with poly(A)‐binding (PAB) proteins. The 7‐bp deletion in GsERD15B promoter enhanced the salt tolerance of soybean, with increased up‐regulation of GsERD15B, two GmPAB genes, the known stress‐related genes including GmABI1, GmABI2, GmbZIP1, GmP5CS, GmCAT4, GmPIP1:6, GmMYB84 and GmSOS1 in response to salt stress. We propose that natural variation in GsERD15B promoter affects soybean salt tolerance, and overexpression of GsERD15B enhanced salt tolerance probably by increasing the expression levels of genes related to ABA‐signalling, proline content, catalase peroxidase, dehydration response and cation transport.

Plant CaCA superfamily genes with higher tendency to retain after WGD are more gene expression and function differentiated in ion-response. Plants and animals face different environmental stresses but share conserved Ca2+ signaling pathways, such as Ca2+/Cation transport. The Ca2+/cation antiporters superfamily (CaCAs) is an ancient and widespread family of ion-coupled cation transporters found in all kingdoms of life. We analyzed the molecular evolution progress of the family through comparative genomics and phylogenetics of CaCAs genes from plants and animals, grouping these genes into several families and clades, and identified multiple gene duplication retention events, particularly in the CAX (H+/cation exchanger), CCX (cation/Ca2+ exchanger), and NCL (Na+/Ca2+ exchanger-like) families. The tendency of duplication retention differs between families and gene clades. The gene duplication events were probably the result of whole-genome duplication (WGD) in plants and might have led to functional divergence. Tissue and ion-response expression analyses revealed that CaCAs genes with more highly differentiated expression patterns are more likely to be retained as duplicates than those with more conserved expression profiles. Phenotype of Arabidopsis thaliana mutants showed that loss of genes with a greater tendency to be retained after duplication resulted in more severe growth deficiency. CaCAs genes in salt-tolerant species tended to inherit the expression characteristics of their most recent common ancestral genes, with conservative ion-response expression. This study indicates a possible evolutionary scheme for cation transport and illustrates distinct fates and a mechanism for the evolution of gene duplicates. The increased copy numbers of genes and divergences in expression might have contributed to the divergent functions of CaCAs protein, allowing plants to cope with environmental stresses and adapt to a larger number of ecological niches.

The phosphorylation state of two serine residues within the C-terminal domain of AtPIP2;1 (S280, S283) regulates its plasma membrane localization in response to salt and osmotic stress. Here, we investigated whether the phosphorylation state of S280 and S283 also influence AtPIP2;1 facilitated water and cation transport. A series of single and double S280 and S283 phosphomimic and phosphonull AtPIP2;1 mutants were tested in heterologous systems. In Xenopus laevis oocytes, phosphomimic mutants AtPIP2;1 S280D, S283D, and S280D/S283D had significantly greater ion conductance for Na+ and K+ , whereas the S280A single phosphonull mutant had greater water permeability. We observed a phosphorylation-dependent inverse relationship between AtPIP2;1 water and ion transport with a 10-fold change in both. The results revealed that phosphorylation of S280 and S283 influences the preferential facilitation of ion or water transport by AtPIP2;1. The results also hint that other regulatory sites play roles that are yet to be elucidated. Expression of the AtPIP2;1 phosphorylation mutants in Saccharomyces cerevisiae confirmed that phosphorylation influences plasma membrane localization, and revealed higher Na+ accumulation for S280A and S283D mutants. Collectively, the results show that phosphorylation in the C-terminal domain of AtPIP2;1 influences its subcellular localization and cation transport capacity.

Ionic liquid (IL) properties, such as high ionic conductivity under ambient conditions combined with nontoxicity and nonflammability, make them important materials for future technologies. Despite high ion conductivity desired for battery applications, cation transport numbers in ILs are not sufficient enough to attain high power density batteries. Thus, developing novel approaches directed toward improvement of cation transport properties is required for the application of ILs in energy-storing devices. In this effort, we used various experimental techniques to demonstrate that the strategy of mixing ILs with ultrasmall (1.8 nm) nanoparticles (NPs) resulted in melt-processable composites with improved transport numbers for cations at room temperature. This significant enhancement in the transport number was attributed to the specific chemistry of NPs exhibiting a weaker cation and stronger anion coordination at ambient temperature. At high temperature, significantly weakened NP–anion associations promoted a liquid-like behavior of composites, highlighting the melt-processability of these composites. These results show that designing a reversible dynamic noncovalent NP–anion association controlled by the temperature may constitute an effective strategy to control ion diffusion. Our studies provide fundamental insights into mechanisms driving the charge transport and offer practical guidance for the design of melt-processable composites with an improved cation transport number under ambient conditions.

Clayware membrane amalgamated with 20% montmorillonite (M-20), acts as an excellent cost effective proton exchange membrane (PEM) for the application in field-scale microbial fuel cells (MFCs). In this investigation, M-20 membrane was pre-treated by acid (M-A), neutral water (M-N) and alkali (M-B), followed by the determination of the membrane properties to access their applicability in MFCs. With alkali treatment of M-20 membrane, maximum proton mass transfer coefficient of 6 × 10−6 cm s−1 was obtained, which was nearly five times higher than M-A (1.15 × 10−6 cm s−1) and four times higher than the control membrane, M-N. Proton conductivity was also found to be maximum for M-B (17.9 × 10−3 S cm−1), which was four times higher than both M-N (4.4 × 10−3 S cm−1) and M-A (4.6 × 10−3 S cm−1). Oxygen mass transfer coefficient was found to be minimum for M-B (4.02 × 10−5 cm s−1), which was considerably lesser than that observed for M-N (16.2 × 10−5 cm s−1) and M-A (13.8 × 10−5 cm s−1). Cation transport number of M-B (0.15 ± 0.01) was found to be two folds lower than M-N, demonstrating M-B is more selective towards proton transport compared to other cations. The MFC-B with M-B as PEM performed superior as compared with other MFCs, demonstrating coulombic efficiency (CE) of 10.2%, chemical oxygen demand (COD) removal efficiency of 88% and power density of 83.5 mW m−2. On the other hand, MFCs using M-A and M-N as PEM, demonstrated mediocre performance with CE of 6% and 7.6%, COD removal efficiency of 80% and 83% and power density of 40.4 ± 6.2 mW m−2 and 64.0 ± 5.8 mW m−2, respectively. Hence, alkali treatment of clayware ceramic membrane elucidated its appropriateness for proliferating the efficacy of MFCs and these are recommended for scaling up of MFCs.

Single-ion conducting polymers such as ionomers are promising battery electrolyte materials, but it is critical to understand how rates and mechanisms of free cation transport depend on the nanoscale aggregation of cations and polymer-bound anions. We perform coarse-grained molecular dynamics simulations of ionomer melts to understand cation mobility as a function of polymer architecture, background relative permittivity, and corresponding ionic aggregate morphology. In systems exhibiting percolated ionic aggregates, cations diffuse via stepping motions along the ionic aggregates. These diffusivities can be quantitatively predicted by calculating the lifetimes of continuous association between oppositely charged ions, which equal the time scales of the stepping (diffusive) motions. In contrast, predicting cation diffusivity for systems with isolated ionic aggregates requires another time scale. Our results suggest that to improve conductivity the Coulombic interaction strength should be strong enough to favor percolated aggregates but weak enough to facilitate ion dissociation.

Ni–Fe alloy coatings with Nb contents of 0, 4.2 at.%, 7.0 at.% and 9.0 at.% were electrodeposited on ferritic stainless steels for intermediate-temperature solid oxide fuel cell (SOFC) interconnect application. The oxidation behavior, scale-growth mechanisms and electrical performances of the Ni–Fe- and NiFe–Nb-coated steels were then investigated in air at 800 °C corresponding to the cathode environment of SOFC. It was found that the scales formed are mainly composed of an external NiFe2O4 layer and an inner Cr2O3-rich layer after oxidation, with some Nb-rich oxides also observed for the Nb-containing coatings. Doping 4.2 at.%Nb into the coating decreased the growth rate of Cr2O3 and suppressed the formation of voids at the scale/alloy interface, whereas excess Nb impaired the oxidation resistance of the steel. The Nb addition affects the oxide growth direction by suppressing the cation transport. All the coatings decreased the area-specific resistance (ASR) of the steel, with the NiFe–4.2 at.%Nb-coated sample exhibiting the lowest ASR value. The effects of Nb on the oxidation mechanism and electrical properties of the Ni–Fe-coated steels are discussed.

Mammalian Na+/H+ exchanger type I isoform (NHE1) is a ubiquitously expressed membrane protein that regulates intracellular pH (pHi) by removing one intracellular proton in exchange for one extracellular sodium ion. Abnormal activity of the protein occurs in cardiovascular disease and breast cancer. The purpose of this study is to examine the role of negatively charged amino acids of extracellular loop 3 (EL3) in the activity of the NHE protein. We mutated glutamic acid 217 and aspartic acid 226 to alanine, and to glutamine and asparagine, respectively. We examined effects on expression levels, cell surface targeting and activity of NHE1, and also characterized affinity for extracellular sodium and lithium ions. Individual mutation of these amino acids had little effect on protein function. However, mutation of both these amino acids together impaired transport, decreasing the Vmax for both Na+ and Li+ ions. We suggested that amino acids E217 and D226 form part of a negatively charged coordination sphere, which facilitates cation transport in the NHE1 protein.

The human ether-á-go-go–related gene (hERG1) channel conducts small outward K(+) currents that are critical for cardiomyocyte membrane repolarization. The gain-of-function mutation N629D at the outer mouth of the selectivity filter (SF) disrupts inactivation and K(+)-selective transport in hERG1, leading to arrhythmogenic phenotypes associated with long-QT syndrome. Here, we combined computational electrophysiology with Markov state model analysis to investigate how SF-level gating modalities control selective cation transport in wild-type (WT) and mutant (N629D) hERG1 variants. Starting from the recently reported cryogenic electron microscopy (cryo-EM) open-state channel structure, multiple microseconds-long molecular-dynamics (MD) trajectories were generated using different cation configurations at the filter, voltages, electrolyte concentrations, and force-field parameters. Most of the K(+) permeation events observed in hERG1-WT simulations occurred at microsecond timescales, influenced by the spontaneous dehydration/rehydration dynamics at the filter. The SF region displayed conductive, constricted, occluded, and dilated states, in qualitative agreement with the well-documented flickering conductance of hERG1. In line with mutagenesis studies, these gating modalities resulted from dynamic interaction networks involving residues from the SF, outer-mouth vestibule, P-helices, and S5–P segments. We found that N629D mutation significantly stabilizes the SF in a state that is permeable to both K(+) and Na(+), which is reminiscent of the SF in the nonselective bacterial NaK channel. Increasing the external K(+) concentration induced “WT-like” SF dynamics in N629D, in qualitative agreement with the recovery of flickering currents in experiments. Overall, our findings provide an understanding of the molecular mechanisms controlling selective transport in K(+) channels with a nonconventional SF sequence.

Understanding cation (H+ , Li+ , Na+ , Al3+ , etc.) intercalation/de-intercalation chemistry in transition metal compounds is crucial for the design of cathode materials in aqueous electrochemical cells. Here we report that orthorhombic vanadium oxides (V2 O5 ) supports highly reversible proton intercalation/de-intercalation reactions in aqueous media, enabling aluminum electrochemical cells with extended cycle life. Empirical analyses using vibrational and x-ray spectroscopy are complemented with theoretical analysis of the electrostatic potential to establish how and why protons intercalate in V2 O5 in aqueous media. We show further that cathode coatings composed of cation selective membranes provide a straightforward method for enhancing cathode reversibility by preventing anion cross-over in aqueous electrolytes. Our work sheds light on the design of cation transport requirements for high-energy reversible cathodes in aqueous electrochemical cells.

Precise control over the shape and elemental composition of colloidal nanocrystals (NCs) is challenging, especially for anisotropic growth. While the most studied nanocrystal syntheses involve homogenous nucleation and growth, the solution-based approach involving heterogenous growth from ion conductive seeds has proved to be very efficient yet less explored. The static nature and superionic conductivity of the seeds enable rapid cation transport for catalysis of defect-free, phase pure NC growth. This review aims to explain the significance of ion-conductive solid seed-based synthesis from a mechanistic point of view to produce 1D and quasi-1D NCs for applications such as photocatalysis, photovoltaics, and photodetectors. We highlight the significant synthetic information reported for heterostructure and alloyed metal chalcogenide NCs synthesized via solution–solid–solid and diffusion-controlled growth based on several kinetic and thermodynamic growth parameters. We also provide a perspective on the areas that hold promise and are in need of further development.

Although the record efficiency of 25.2% was achieved using a 500–1000 nm-thick perovskite film within an appropriate device structure, it is desirable to achieve high efficiency with a thinner perovskite film because the thinner layer can gain benefits of lowering Pb content, reducing cost and better adjustability for a transparent window, flexible device and tandem structure. Here, we report on a high efficiency thin film (

Swept frequency electrical impedance spectroscopy (EIS) can be used in conjunction with tethered bilayer lipid membranes to monitor the membrane permeability of ions in real-time (Deplazes et al. J Phys Chem Lett 11:6353-6358, 2020). Conductance readings, as determined by EIS, are a measure of the ability of ions to be transported across membranes. Recording the change in conductance as a function of cation concentration and a comparison between a range of cations permits conclusions to be made about the specificity of cation transport through pores. An estimate for upper pore size and cation selectivity of ion channels can be established using this method.

Chronopotentiometry and electromotive force methods were used to determine ion transport numbers in two homogeneous and highly selective cation- and anion-exchange membranes. NaCl aqueous solutions of different concentrations, varying from 1 mol·m−3 to 100 mol·m−3 were used to analyze the possible impact of the electrolyte concentration on the results obtained by both methods. Cation transport numbers close to unity for the cation exchange membrane and to zero for the anion-exchange membrane were found for both membrane types with both methods when the NaCl-concentration exceeded 10 mol·m−3. At the lowest concentrations, a systematic deviation from ideal behavior was seen, mainly in the electromotive force method, possibly due to a higher contribution from transport of water. The cation transport number estimated by the electromotive force method was systematically lower than the number obtained from chronopotentiometry, probably due to larger concentration polarization at low electrolyte concentration. We conclude that chronopotentiometry is a relatively rapid and precise technique for ion transport number determination at electrolyte concentrations for which membranes maintain a good selectivity for the measurement conditions used.

The Malpighian (renal) tubule is capable of transporting fluid at remarkable rates. This review will focus on recent insights into the mechanisms by which these high rates are achieved and controlled, with particular reference to the tubules of Drosophila melanogaster, in which the combination of physiology and genetics has led to particularly rapid progress. Like many vertebrate epithelia, the Drosophila tubule has specialized cell types, with active cation transport confined to a large, metabolically active principal cell; whereas the smaller intercalated stellate cell controls chloride and water shunts to achieve net fluid secretion. Recently, the genes underlying many of these processes have been identified, functionally validated and localized within the tubule. The imminent arrival of new types of post-genomic data (notably single cell sequencing) will herald an exciting era of new discovery.

CNNM2 (Cystathionine-β-synthase-pair Domain Divalent Metal Cation Transport Mediator 2) pathogenic variants have been reported to cause hypomagnesemia, epilepsy, and intellectual disability/developmental delay (ID/DD). We identified two new cases with CNNM2 novel de novo pathogenic variants, c.814T>C and c.976G>C. They both presented with infantile-onset epilepsy with DD and hypomagnesemia refractory to magnesium supplementation. To date, 21 cases with CNNM2-related disorders have been reported. We combined all 23 cases to analyze the features of CNNM2-related disorders. The phenotypes can be classified into three types: type 1, autosomal dominant (AD) inherited simple hypomagnesemia; type 2, AD inherited hypomagnesemia with epilepsy and ID/DD; and type 3, autosomal recessive (AR) inherited hypomagnesemia with epilepsy and ID/DD. All five type 1 cases had no epilepsy or ID/DD; they all had hypomagnesemia, and three of them presented with symptoms secondary to hypomagnesemia. Fifteen type 2 patients could have ID/DD and seizures, which can be controlled with antiseizure medications (ASMs); their variations clustered in the DUF21 domain of CNNM2. All three type 3 patients had seizures from 1 to 6 days after birth; the seizures were refractory, and 1/3 had status epilepticus; ID/DD in these AR-inherited cases was more severe than that of AD-inherited cases; they all had abnormalities of brain magnetic resonance imaging (MRI). Except for one patient whose serum magnesium was the lower limit of normal, others had definite hypomagnesemia. Hypomagnesemia could be improved after magnesium supplement but could not return to the normal level. Variations in the CBS2 domain may be related to lower serum magnesium. However, there was no significant difference in the level of serum magnesium among the patients with three different types of CNNM2-related disorders. The severity of different phenotypes was therefore not explained by decreased serum magnesium. We expanded the spectrum of CNNM2 variants and classified the phenotypes of CNNM2-related disorders into three types. We found that DUF21 domain variations were most associated with CNNM2-related central nervous system phenotypes, whereas hypomagnesemia was more pronounced in patients with CBS2 domain variations, and AR-inherited CNNM2-related disorders had the most severe phenotype. These results provide important clues for further functional studies of CNNM2 and provide basic foundations for more accurate genetic counseling.

In this study, we characterize the response of the free-living oligotrophic alphaproteobacterium Caulobacter crescentus to low temperatures by global transcriptomic analysis. Our results showed that 656 genes were upregulated and 619 were downregulated at least 2-fold after a temperature downshift. The identified differentially expressed genes (DEG) belong to several functional categories, notably inorganic ion transport and metabolism, and a subset of these genes had their expression confirmed by reverse transcription quantitative real-time PCR (RT-qPCR). Several genes belonging to the ferric uptake regulator (Fur) regulon were downregulated, indicating that iron homeostasis is relevant for adaptation to cold. Several upregulated genes encode proteins that interact with nucleic acids, particularly RNA: cspA, cspB, and the DEAD box RNA helicases rhlE, dbpA, and rhlB. Moreover, 31 small regulatory RNAs (sRNAs), including the cell cycle-regulated noncoding RNA (ncRNA) CcnA, were upregulated, indicating that posttranscriptional regulation is important for the cold stress response. Interestingly, several genes related to transport were upregulated under cold stress, including three AcrB-like cation/multidrug efflux pumps, the nitrate/nitrite transport system, and the potassium transport genes kdpFABC. Further characterization showed that kdpA is upregulated in a potassium-limited medium and at a low temperature in a SigT-independent way. kdpA mRNA is less stable in rho and rhlE mutant strains, but while the expression is positively regulated by RhlE, it is negatively regulated by Rho. A kdpA-deleted strain was generated, and its viability in response to osmotic, acidic, or cold stresses was determined. The implications of such variation in the gene expression for cold adaptation are discussed. IMPORTANCE Low-temperature stress is an important factor for nucleic acid stability and must be circumvented in order to maintain the basic cell processes, such as transcription and translation. The oligotrophic lifestyle presents further challenges to ensure the proper nutrient uptake and osmotic balance in an environment of slow nutrient flow. Here, we show that in Caulobacter crescentus, the expression of the genes involved in cation transport and homeostasis is altered in response to cold, which could lead to a decrease in iron uptake and an increase in nitrogen and high-affinity potassium transport by the Kdp system. This previously uncharacterized regulation of the Kdp transporter has revealed a new mechanism for adaptation to low temperatures that may be relevant for oligotrophic bacteria.

Alkali metal thermoelectric converter (AMTEC) is a clean energy converter that can be coupled with biomass for power generation. In present research, the transport of heat and cation was investigated in NaK-BASE tubes prepared at different sintered temperatures. The heat conduction and the fractal model were employed to investigate the temperature distributions based on the microstructures of the NaK-BASE tubes sintered at different temperatures, and the transport of Na+ and K+ in NaK-BASE tube was simulated by Poisson-Nernst-Planck multi-ions transport model, and the cation concentrations and surface charge densities were obtained in the NaK-BASE tubes with different temperatures. The results showed that microstructure of the NaK-BASE was related to the sintered temperature, and the microstructure of the NaK-BASE impacted the temperature distribution, the cation concentration and the surface charge density of Na+ and K+ in the NaK-BASE tubes. At the same heat source temperature, the average temperature in the NaK-BASE prepared at high sintered temperature was higher than that prepared at low sintered temperature. In addition, the increase of the average temperature resulted in the increase of the cation concentration and the surface charge density of Na+ and K+ in the NaK-BASE, therefore, the performance of the NaK-AMTEC could be enhanced by increasing the sintered temperature and the average temperature of the NaK-BASE.

Membrane-bound inorganic pyrophosphatase (mPPase) resembles the F-ATPase in catalyzing polyphosphate-energized H+ and Na+ transport across lipid membranes, but differs structurally and mechanistically. Homodimeric mPPase likely uses a “direct coupling” mechanism, in which the proton generated from the water nucleophile at the entrance to the ion conductance channel is transported across the membrane or triggers Na+ transport. The structural aspects of this mechanism, including subunit cooperation, are still poorly understood. Using a refined enzyme assay, we examined the inhibition of K+-dependent H+-transporting mPPase from Desulfitobacterium hafniensee by three non-hydrolyzable PPi analogs (imidodiphosphate and C-substituted bisphosphonates). The kinetic data demonstrated negative cooperativity in inhibitor binding to two active sites, and reduced active site performance when the inhibitor or substrate occupied the other active site. The nonequivalence of active sites in PPi hydrolysis in terms of the Michaelis constant vanished at a low (0.1 mM) concentration of Mg2+ (essential cofactor). The replacement of K+, the second metal cofactor, by Na+ increased the substrate and inhibitor binding cooperativity. The detergent-solubilized form of mPPase exhibited similar active site nonequivalence in PPi hydrolysis. Our findings support the notion that the mPPase mechanism combines Mitchell’s direct coupling with conformational coupling to catalyze cation transport across the membrane.

Współczesna idea kliniczna choroby afektywnej dwubiegunowej (ChAD) została ukształtowana jako pokłosie pomysłu Emila Kraepelina nazwanego „manisch-depressives Irresein” sformułowanego w 1899 roku, z istotnymi modyfikacjami w ciągu ostatniego półwiecza. Obecny paradygmat etiopatogenetyczny ChAD postuluje pojawienie się choroby w wyniku interakcji czynników genetycznych i epigenetycznych z wpływami środowiskowymi. Największe znaczenie dla genetyki molekularnej ChAD miała analiza tzw. genów kandydujących oraz badania asocjacji całego genomu (genome-wide association studies – GWAS). Profil genetyczny ChAD zawiera wiele genów predyspozycji do innych zaburzeń psychicznych. Zaburzenia epigenetyczne stanowią mechanizm pośredniczący dla wpływu czynników środowiskowych we wczesnym okresie życia. Niektóre koncepcje neurobiologiczne ChAD mają genezę farmakologiczną wynikającą z mechanizmów działania stosowanych leków. Należą do nich teorie: katecholaminowa, zaburzeń transportu kationów i purynergiczna. Koncepcje takie, jak zaburzenia neuroplastyczności, teoria „zapalna” oraz dysfunkcja osi stresowej, powstały jako ekstrapolacja początkowych hipotez patogenetycznych depresji. Nowe teorie patogenetyczne związane z ChAD dotyczą zaburzeń rytmów biologicznych oraz dysfunkcji mitochondriow i stresu oksydacyjnego. W ChAD występują nieprawidłowości w zakresie czynności struktur mózgu, zwłaszcza tzw. przedniej sieci limbicznej. Patogenetyczne wpływy środowiskowe w ChAD obejmują czynniki działające w ciąży, traumę wczesnodziecięcą i wydarzenia stresowe późniejszego okresu życia, a także uwarunkowania sezonowe i klimatyczne. Zarówno patogeneza, jak i przebieg ChAD ujmowane są obecnie w kontekście rozwojowym czego wyrazem są koncepcje etapów przebiegu (stagingu) tej choroby.

Corynebacterium glutamicum has been widely used for bulk and fine chemicals fermentation these years. In this study, we developed a defined medium for this bacteria based on the widely used CGXII minimal medium. We evaluated the effects of different components in CGXII on cell growth of C. glutamicum ATCC 13032 and improved the medium through single-factor experiment and central composite design (CCD). Urea, K(2)HPO(4) and MgSO(4) were found to be significant factors. 7 out of the total 15 components were modified. (NH(4))(2)SO(4), KH(2)PO(4), and protocatechuic acid were eliminated. Amounts of urea and MgSO(4) were increased, and concentrations of biotin and glucose were reduced. The resulting R2 medium was proved to be more suitable for cell growth, plasmid amplification and protein production than the original recipe. Remarkably, cell biomass accumulation in R2 increased by 54.36% than CGXII. Transcriptome analysis revealed alteration of carbon metabolism, cation transport and energy synthesis, which might be beneficial for cell growth in R2. Considering the high nitrogen content and availability of urea, the new medium is simplified and cost effective, which holds attractive potential for future study. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02959-6.

We present mathematical simulations of shapes of red blood cells (RBCs) and their cytoskeleton when they are subjected to linear strain. The cell surface is described by a previously reported quartic equation in three dimensional (3D) Cartesian space. Using recently available functions in Mathematica to triangularize the surfaces we computed four types of curvature of the membrane. We also mapped changes in mesh-triangle area and curvatures as the RBCs were distorted. The highly deformable red blood cell (erythrocyte; RBC) responds to mechanically imposed shape changes with enhanced glycolytic flux and cation transport. Such morphological changes are produced experimentally by suspending the cells in a gelatin gel, which is then elongated or compressed in a custom apparatus inside an NMR spectrometer. A key observation is the extent to which the maximum and minimum Principal Curvatures are localized symmetrically in patches at the poles or equators and distributed in rings around the main axis of the strained RBC. Changes on the nanometre to micro-meter scale of curvature, suggest activation of only a subset of the intrinsic mechanosensitive cation channels, Piezo1, during experiments carried out with controlled distortions, which persist for many hours. This finding is relevant to a proposal for non-uniform distribution of Piezo1 molecules around the RBC membrane. However, if the curvature that gates Piezo1 is at a very fine length scale, then membrane tension will determine local curvature; so, curvatures as computed here (in contrast to much finer surface irregularities) may not influence Piezo1 activity. Nevertheless, our analytical methods can be extended address these new mechanistic proposals. The geometrical reorganization of the simulated cytoskeleton informs ideas about the mechanism of concerted metabolic and cation-flux responses of the RBC to mechanically imposed shape changes.