Membrane Channels Research Articles

Computational simulation of mass transfer in membranes using hybrid machine learning models and computational fluid dynamics

In this work, a modeling approach has been developed for describing component separation by selective membrane systems. The developed modeling strategy in this research is based on computational fluid dynamics (CFD) integrated with machine learning (ML) approach to reduce the computational costs and evaluate the possibility of ML model for integration to CFD models. The considered case study is a membrane-based molecular separation for removal of species from water. CFD was performed to solve mass transfer equations, and the data in form of concentration profiles have been used for ML computations. The data set in this research has about two thousand data vectors, each of which contains two inputs r and z and one output C which is the species concentration in the feed channel of membrane. Three models, Multi-Layer Perceptron (MLP), Support Vector Machines with RBF kernel (RBF-SVM), and Decision Tree (DT) were chosen for modeling since they were anticipated to perform well on the provided data by adjusting their hyper-parameters. After optimizing the models, their results were carefully checked with different criteria. All three models showed acceptable results with R2 score criteria higher than 0.9. MAPE decreased to 3.57 × 10−3 and improved to 3.6 with the RMSE criterion. We can introduce the best model in this research as the MLP model for description of the mass transfer in the membrane.

Therapeutic potential of phytochemicals for cystic fibrosis.

The aim of this review was to review and discuss various phytochemicals that exhibit beneficial effects on mutated membrane channels, and hence, improve transmembrane conductance. These therapeutic phytochemicals may have the potential to decrease mortality and morbidity of CF patients. Four databases were searched using keywords. Relevant studies were identified, and related articles were separated. Google Scholar, as well as gray literature (i.e., information that is not produced by commercial publishers), were also checked for related articles to locate/identify additional studies. The relevant databases were searched a second time to ensure that recent studies were included. In conclusion, while curcumin, genistein, and resveratrol have demonstrated effectiveness in this regard, it should be emphasized that coumarins, quercetin, and other herbal medicines also have beneficial effects on transporter function, transmembrane conductivity, and overall channel activity. Additional in vitro and in vivo studies should be conducted on mutant CFTR to unequivocally define the mechanism by which phytochemicalsalter transmembrane channel function/activity, since the results of the studies evaluated in this review have a high degree of heterogenicity and discrepancy. Finally, continued research be undertaken to clearly define the mechanism(s) of action and the therapeutic effects that therapeutic phytochemicals have on the symptoms observed in CF patients in an effort to reduce mortality and morbidity.

Influence of Membrane Asymmetry on OmpF Insertion, Orientation and Function.

The effect of asymmetric membranes containing lipopolysaccharides (LPS) on the outer membrane protein F (OmpF) reconstitution, channel orientation, and antibiotic permeation across the outer membrane was investigated. After forming an asymmetric planar lipid bilayer composed of LPS on one and phospholipids on the other side, the membrane channel OmpF was added. The ion current recordings demonstrate that LPS has a strong influence on the OmpF membrane insertion, orientation, and gating. Enrofloxacin was used as an example of an antibiotic interacting with the asymmetric membrane and with OmpF. The enrofloxacin caused the blockage of the ion current through the OmpF, depending on the side of addition, the transmembrane voltage applied, and the composition of the buffer. Furthermore, the enrofloxacin changed the phase behavior of the LPS-containing membranes, demonstrating that its membrane activity influences the function of OmpF and potentially the membrane permeability.

Uterus proliferative period ceRNA network of Yunshang black goat reveals candidate genes on different kidding number trait.

Pregnancy loss that occurs in the uterus is an important and widespread problem in humans and farm animals and is also a key factor affecting the fecundity of livestock. Understanding the differences in the fecundity of goats may be helpful in guiding the breeding of goats with high fecundity. In this study, we performed RNA sequencing and bioinformatics analysis to study the uterus of Yunshang black goats with high and low fecundity in the proliferative period. We identified mRNAs, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) by analyzing the uterine transcriptomes. The target genes of the identified miRNAs and lncRNAs were predicted, and miRNA-mRNA interaction and competitive endogenous RNA (ceRNA) networks were constructed. By comparisons between low- and high-fecundity groups, we identified 1,674 differentially expressed mRNAs (914 were upregulated, and 760 were downregulated), 288 differentially expressed lncRNAs (149 were upregulated, and 139 were downregulated), and 17 differentially expressed miRNAs (4 were upregulated, and 13 were downregulated). In addition, 49 miRNA-mRNA pairs and 45 miRNA-lncRNA pairs were predicted in the interaction networks. We successfully constructed a ceRNA interaction network with 108 edges that contained 19 miRNAs, 11 mRNAs, and 73 lncRNAs. Five candidate genes (PLEKHA7, FAT2, FN1, SYK, and ITPR2) that were annotated as cell adhesion or calcium membrane channel protein were identified. Our results provide the overall expression profiles of mRNAs, lncRNAs, and miRNAs in the goat uterus during the proliferative period and are a valuable reference for studies into the mechanisms associated with the high fecundity, which may be helpful to guide goat to reduce pregnancy loss.

A common mechanism of Sec61 translocon inhibition by small molecules.

The Sec61 complex forms a protein-conducting channel in the endoplasmic reticulum membrane that is required for secretion of soluble proteins and production of many membrane proteins. Several natural and synthetic small molecules specifically inhibit Sec61, generating cellular effects that are useful for therapeutic purposes, but their inhibitory mechanisms remain unclear. Here we present near-atomic-resolution structures of human Sec61 inhibited by a comprehensive panel of structurally distinct small molecules-cotransin, decatransin, apratoxin, ipomoeassin, mycolactone, cyclotriazadisulfonamide and eeyarestatin. All inhibitors bind to a common lipid-exposed pocket formed by the partially open lateral gate and plug domain of Sec61. Mutations conferring resistance to the inhibitors are clustered at this binding pocket. The structures indicate that Sec61 inhibitors stabilize the plug domain in a closed state, thereby preventing the protein-translocation pore from opening. Our study provides the atomic details of Sec61-inhibitor interactions and the structural framework for further pharmacological studies and drug design.

Selective Activation of Cells by Piezoelectric Molybdenum Disulfide Nanosheets with Focused Ultrasound.

An accurate method for neural stimulation within the brain could be very useful for treating brain circuit dysfunctions and neurological disorders. With the aim of developing such a method, this study investigated the use of piezoelectric molybdenum disulfide nanosheets (MoS2 NS) to remotely convert ultrasound energy into localized electrical stimulation in vitro and in vivo. The application of ultrasound to cells surrounding MoS2 NS required only a single pulse of 2 MHz ultrasound (400 kPa, 1,000,000 cycles, and 500 ms pulse duration) to elicit significant responses in 37.9 ± 7.4% of cells in terms of fluxes of calcium ions without detectable cellular damage. The proportion of responsive cells was mainly influenced by the acoustic pressure, number of ultrasound cycles, and concentration of MoS2 NS. Tests using appropriate blockers revealed that voltage-gated membrane channels were activated. In vivo data suggested that, with ultrasound stimulation, neurons closest to the MoS2 NS were 3-fold more likely to present c-Fos expression than cells far from the NS. The successful activation of neurons surrounding MoS2 NS suggests that this represents a method with high spatial precision for selectively modulating one or several targeted brain circuits.

Drugging aquaporins

Water is essential for all life because it is required for the proper functioning of the cells and tissues of all organisms. It crosses biological membranes down osmotic gradients through the pores of aquaporin membrane channels at rates of up to 3 billion molecules per second. In the twenty years since Peter Agre was awarded the 2003 Nobel Prize in Chemistry for the discovery of the aquaporin family, aquaporin structure and function have become established in the literature. As a consequence, we understand in fine detail the mechanism by which aquaporins facilitate membrane water flow while excluding protons. We also know that some aquaporins facilitate the permeation of other small neutral solutes, ions or even unexpected substrates across biological membranes. The thirteen aquaporins in the human body have been implicated in pathologies including oedema, epilepsy, cancer cell migration, tumour angiogenesis, metabolic disorders and inflammation. Surprisingly, however, there is no aquaporin-targeted drug in the clinic. Some scientists have therefore concluded that aquaporins are intrinsically non-druggable targets. Discovering medicines to treat disorders of water homeostasis is thus an enduring challenge for the aquaporin field. Success in this endeavour will meet the urgent clinical need of millions of patients suffering from a range of life-threatening conditions and for whom no pharmacological interventions are currently available.

Vascular signaling plasticity reprograms neurovascular coupling pathways to precisely match energy delivery to neuronal metabolic needs

Neuronal computation is metabolically expensive and relies on the timely delivery of energy substrates via tightly controlled blood flow to prevent energetic deficits. The range of mechanisms responsible for this coupling of neural activity to blood flow are collectively termed ‘neurovascular coupling’ (NVC). These NVC mechanisms are typically assumed to be invariant and the possibility that they may be plastic, allowing reshaping of energy delivery according to ever-shifting neuronal metabolic needs, has not been considered. We present evidence that neuronal activity resculpts blood flow control mechanisms inherent to the endothelium, which forms the inner lining of all blood vessels, through a process we refer to as vascular signalling plasticity (VSP). Using an environmental enrichment paradigm, we find that housing mice in an environment that increases input to the barrel cortex drives profound synaptic plasticity within this network. This is accompanied by a remarkable resculpting of local vascular reactivity, augmenting the efficacy of mechanisms that signal for an increase in blood flow. This increase in sensitivity manifests as an increase red blood cell flux to capillary stimulation with extracellular K+, which activates strong inward rectifier K+ (Kir2.1) channel-dependent capillary-to-arteriole electrical signalling to elicit hyperemia. To support this augmentation, we find that VSP induces a ~70% increase in the density of Kir2.1 channels in endothelial cells membranes which is underlain by transcriptional and translational changes in capillary ECs. Using an ex vivo capillary-arteriole preparation, we demonstrate that this increase in membrane Kir2.1 channels translates into a profound shift in the sensitivity of capillaries to K+ stimulation to evoke upstream arteriolar dilation. Together, these results suggest that increasing neuronal energy consumption leads to a profound potentiation of the retrograde hyperpolarization generated by the endothelium during activity, enhancing upstream dilation at the penetrating arteriole and augmenting blood delivery to match enhanced local needs. Our data thus recast the capillary bed as a plastic, brain-wide, neural activity sensing network that is modulated at the molecular level by local neural input. This allows fine-tuning of existing blood delivery mechanisms to meet continually fluctuating neural energy needs. VSP represents a novel facet of brain plasticity that may be utilised by various physiological processes and may be disrupted in aging and in the broad range of brain pathologies that have a vascular component. Support for this work was provided by the NIH National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645, 5R01NS115401 [PI: S. Sakadžić], and 1DP2NS121347-01, to T.A.L), the American Heart Association (Awards 17SDG33670237 and 19IPLOI34660108 to T.A.L) and an NIH S10 grant (S10 OD026698, to University of Maryland School of Medicine CIBR Core Confocal Facility). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Connexin-43: More than just a gap junction protein. Connexin-43 controls CD4+ T cell activation and clonal expansion

Abstract Activation and proliferation of antigen specific T cells depends on the interaction of multiple signaling molecules with the TCR/CD3 complex. We report that expression of connexin 43 (Cx43), a gap junction protein, is critical for the expansion of antigen-specific or self-reactive effector CD4 +T cells. While gap junction mediated intercellular communication has been the main focus of connexin research, the cytoplasmic C-terminus of Cx43 has multiple functions independent of membrane channel forming properties and may act as a docking molecule for assembling signaling complexes including the immunological synapse. We also report that antigen-specific Cx43-deficient CD4 +T cells transferred into recipient mice immunized with cognate antigenic peptide and adjuvant expanded poorly compared to wild type cells. This protected mice from experimental autoimmune encephalomyelitis (EAE). Decreased proliferation and expansion also protects lymphopenic mice repopulated with naive, Cx43 deficient CD4 +T cells, from inflammatory bowel disease. We have found that Cx43-deficient CD4 +T cells have a signaling defect affecting Erk, p38 and Akt signaling pathways. Transcriptome RNA-seq analysis comparing gene expression profiles of activated Cx43 sufficient and deficient CD4 +T cells shows that differentially expressed genes are enriched in genes involved in G protein and Ca 2+signaling, ATP metabolism, genes regulating cytoskeleton reorganization and T cell homing. In summary, our data demonstrate that Cx43 has a major impact on the generation of effector CD4 +T cells, their ability to respond to antigenic stimulation, or to precipitate autoimmune disease.

Mild ultraviolet detemplation of SAPO-34 zeolite membranes toward pore structure control and highly selective gas separation

SAPO-34 zeolite membranes were activated by ultraviolet (UV) radiation at low temperatures to reduce grain boundary defects. The successful detemplation of SAPO-34 zeolite powders using UV radiation was confirmed by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and nitrogen adsorption-desorption. The irradiance exerted a significant impact on the quality of UV-detemplated SAPO-34 membranes. Under optimal UV detemplation conditions, SAPO-34 membranes showed a moderate H2 permeance of ∼10−7 mol Pa−1 m−2 s−1, with a H2/i-C4H10 permselectivity over 75 under room temperature. The membranes showed an exceptionally low CO2 permeance in comparison with N2 and CH4 despite the smaller molecular size of CO2, resulting in an unprecedentedly high H2/CO2 permselectivity over 50, which was ascribed mainly to the intense interaction between the CO2 molecules and confined organic structure directing agent (OSDA) residue in membrane channels. The temperature dependence of singe-gas permeance through SAPO-34 zeolite membranes showed that gases, including He, H2, CO2, CH4, C2H6, C3H8, and i-C4H10, markedly increased as the temperature increased, indicating an activated diffusion mechanism. The activation energies for H2 permeation through the SAPO-34 membranes were 17–23 kJ mol−1, which were reasonable based on the correlation between the activation energy for H2 permeation and the average pore size for reported membranes by assuming minimal grain boundary defects in the UV-detemplated SAPO-34 membranes.

Dissociation Between Neuronal and Astrocytic Calcium Activity in Response to Locomotion in Mice.

Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca2+) imaging of these two cell types in the somatosensory cortex in head-fixed mice moving on the airlifted platform. Ca2+ activity in astrocytes significantly increased during locomotion from a low quiescence level. Ca2+ signals first appeared in the distal processes and then propagated to astrocytic somata, where it became significantly larger and exhibited oscillatory behaviour. Thus, astrocytic soma operates as both integrator and amplifier of Ca2+ signal. In neurons, Ca2+ activity was pronounced in quiescent periods and further increased during locomotion. Neuronal Ca2+ concentration ([Ca2+]i) rose almost immediately following the onset of locomotion, whereas astrocytic Ca2+ signals lagged by several seconds. Such a long lag suggests that astrocytic [Ca2+]i elevations are unlikely to be triggered by the activity of synapses among local neurons. Ca2+ responses to pairs of consecutive episodes of locomotion did not significantly differ in neurons, while were significantly diminished in response to the second locomotion in astrocytes. Such astrocytic refractoriness may arise from distinct mechanisms underlying Ca2+ signal generation. In neurons, the bulk of Ca2+ enters through the Ca2+ channels in the plasma membrane allowing for steady-level Ca2+ elevations in repetitive runs. Astrocytic Ca2+ responses originate from the intracellular stores, the depletion of which affects subsequent Ca2+ signals. Functionally, neuronal Ca2+ response reflects sensory input processed by neurons. Astrocytic Ca2+ dynamics is likely to provide metabolic and homeostatic support within the brain active milieu.

1D Continuous Subnanofiltration with Ultrahigh Physical Selectivity for HS− Ion

In almost all cellular phenomena and life activities, transmembrane exchange of signals and metabolites is indispensable, and heavily dependent on high selectivity of membrane pores and channels. The involved principles of natural selectivity are widely inspired and adopted for future membrane design, but often limited by the geometry of those artificial channels. Herein, a smectic liquid crystal polymeric (SmP) membrane embedded with tubular cut‐through pillar[5]arene dimers (P5Ds) by self‐assembly is first constructed. The physical confinement effect of inner subnanosized P5D cavity enables SmP membrane to behave with 1D continuous hydrogen sulfide ion (HS−) flow and ultrahigh physical selectivity for HS−. The simulated calculations and corresponding energy analyses show that it is essentially attributed to the size of ion–water cluster, not its own size. It is anticipated to provide a highly precise platform for separation and detection of human endogenous hydrogen sulfide as representative biomarker.

Bacterial spore germination receptors are nutrient-gated ion channels.

Bacterial spores resist antibiotics and sterilization and can remain metabolically inactive for decades, but they can rapidly germinate and resume growth in response to nutrients. Broadly conserved receptors embedded in the spore membrane detect nutrients, but how spores transduce these signals remains unclear. Here, we found that these receptors form oligomeric membrane channels. Mutations predicted to widen the channel initiated germination in the absence of nutrients, whereas those that narrow it prevented ion release and germination in response to nutrients. Expressing receptors with widened channels during vegetative growth caused loss of membrane potential and cell death, whereas the addition of germinants to cells expressing wild-type receptors triggered membrane depolarization. Therefore, germinant receptors act as nutrient-gated ion channels such that ion release initiates exit from dormancy.

Cationic stabilized layered graphene oxide (GO) membrane for shale gas wastewater treatment: An atomistic insight

In recent years graphene oxide (GO) membranes have emerged as one of the most promising candidates for wastewater treatment. However, one major issue with layered GO membranes is their tendency to swell in an aqueous environment. Cation intercalation inside the interlayer gallery of layered GO membrane is one of the promising solutions to mitigate this problem. However, the effect of cationic concentration inside membrane channels on the mechanism of water permeance and salt rejection is yet to be investigated in detail. This study investigates shale gas wastewater (NaCl, CaCl2, and crude oil) treatment via nonequilibrium molecular dynamics (MD) simulations with cation (K+, Mg2+) intercalated GO membranes. The effect of cationic concentration on water permeance and salt rejection has been presented in detail. This study reveals that the presence of a higher concentration of cations inside the GO membrane induces higher water resistance in the membrane. In addition to the concentration of intercalated ions, interlayer distance also plays a significant role in determining water permeance. We observed that Mg2+ ion intercalated and K+ ion intercalated GO membranes maintain an interlayer distance of around 13.6 Å and 11.4 Å, respectively. As a result, Mg2+ ion intercalated GO membranes exhibit superior water permeance than K+ ion intercalated GO membranes. We also observed a difference in the crude oil aggregate formation (a composition of alkanes, cycloalkanes, and aromatics) in the two systems (more stable aggregate in K+ ion intercalated GO membrane system as compared to Mg2+ ion intercalated GO membrane system) during the forward osmosis (FO) process. This can be attributed to weaker interactions of K+ ions with the crude oil and lower water permeance of K+ ion intercalated GO membranes than Mg2+ ion intercalated GO membranes. This aggregate formation is an important factor for crude oil rejection. Moreover, aromatics are more concentrated at the crude oil-water interface than other hydrocarbons. On the other hand, more cations inside the GO membrane layers results in better Na+ rejection but decreased Cl− rejection.

Determination of the effect of silica nanoparticles on TRP currents in retinal pigment epithelial cells by entropy measurement

Ion channels in cell membranes are gated, water-filled pores that allow passive transport of ions across the membrane along their electrochemical gradient. Recent studies have shown that nanoparticles can interact with ion channels and change their currents kinetics properties of the channel. In this study, we used the transient receptor potential (TRP) channel currents in retinal pigment epithelial (RPE) cells recorded by whole-cell patch clamp technique to observe the silica nanoparticle-ion channel interaction. For whole cell recordings, we clamped membrane potential to −40 mV and used a ramp of 1000 ms duration for stimulation. The ramp was increased from −140 mV to +60 mV. We used windowed scalogram entropy and compared the results with windowed scale index method. Our results indicated that the temporal change of entropy using windowed scalogram entropy method is sensitive to demonstrating the effect of silica nanoparticles on RPE cell TRP currents. Furthermore, windowed scale index can analyze the temporal fluctuations in the aperiodicity of cell membrane current signals. Our findings suggest that entropy measurement methods may be useful in the function analysis of cell ion channels.

Critical contribution of the intracellular C-terminal region to TRESK channel activity is revealed by the epithelial Na+ current ratio method

TRESK (K2P18.1) possesses unique structural proportions within the K2P background potassium channel family. The previously described TRESK regulatory mechanisms are based on the long intracellular loop between the second and third transmembrane segments (TMS). However, the functional significance of the exceptionally short intracellular C-terminal region (iCtr) following the fourth TMS has not yet been examined. In the present study, we investigated TRESK constructs modified at the iCtr by two-electrode voltage clamp and the newly developed epithelial sodium current ratio (ENaR) method in Xenopus oocytes. The ENaR method allowed the evaluation of channel activity by exclusively using electrophysiology, and provided data that are otherwise not readily available under whole-cell conditions. TRESK homodimer was connected with two ENaC (epithelial Na+ channel) heterotrimers and the Na+ current was measured as an internal reference, proportional to the number of channels in the plasma membrane. Modifications of TRESK iCtr resulted in diverse functional effects, indicating a complex contribution of this region to K+ channel activity. Mutations of positive residues in proximal iCtr locked TRESK in a low activity, calcineurin-insensitive state, although this phosphatase binds to distant motifs in the loop region. Accordingly, mutations in proximal iCtr may prevent the transmission of modulation to the gating machinery. Replacing distal iCtr with a sequence designed to interact with the inner surface of the plasma membrane increased the activity of the channel to unprecedented levels, as indicated by ENaR and single channel measurements. In conclusion, the distal iCtr is a major positive determinant of TRESK function.

Highly conductive, anti-freezing, and adhesive hydrogels containing pores constructed by cation–dipole interactions

The low ionic conductivity of most hydrogels limits their application in various fields. Boosting ion conductivity in anion exchange membranes (AEMs) using dipole-ion interactions (electrostatic attraction between anions and neutral dipole molecules) with exceptional interaction energies of 20 to 200 kJ mol−1 is the best way to create ion channels in anion exchange membranes (AEMs). In this study, intending to increase the ionic conductivity of hydrogels, the antifreeze crosslinked PVA/PVP hydrogels (5, 10, and 15% Cr-PVA) were prepared using 1,10-dibromodecane (DBD) to crosslink PVA and PVP via SN2 reaction to create multiple pores morphology in the hydrogels by cation-dipole interactions. Moreover, the prepared hydrogels contain cationic groups facilitating ion transport through the hopping mechanism. There was a significant difference in ionic conductivity between the 10% Cr-PVA hydrogel (2.63 S m−1) and the PVA hydrogel (0.76 S m−1) at room temperature due to the multiple pores created with cation-dipole interaction. Despite excellent mechanical properties, 10% Cr-PVA at −20 °C (1.25 S m−1) has a higher ionic conductivity than most antifreeze conductive hydrogels. Eventually, the 10% Cr-PVA hydrogel with gauge factor 1.97 demonstrated the desired sensitive response performance for sensor applications.

Transient Receptor Potential Canonical 6 (TRPC6) Channel in the Pathogenesis of Diseases: A Jack of Many Trades.

The mammalian Transient Receptor Potential Canonical (TRPC) subfamily comprises seven transmembrane proteins (TRPC1-7) forming cation channels in the plasma membrane of mammalian cells. TRPC channels mediate Ca2+ and Na+ influx into the cells. Amongst TRPCs, TRPC6 deficiency or increased activity due to gain-of-function mutations has been associated with a multitude of diseases, such as kidney disease, pulmonary disease, and neurological disease. Indeed, the TRPC6 protein is expressed in various organs and is involved in diverse signalling pathways. The last decade saw a surge in the investigative studies concerning the physiological roles of TRPC6 and describing the development of new pharmacological tools modulating TRPC6 activity. The current review summarizes the progress achieved in those investigations.

Muscle velocity recovery cycles in myopathy

ObjectiveTo understand the pathophysiology of myopathies by using muscle velocity recovery cycles (MVRC) and frequency ramp (RAMP) methodologies. Methods42 patients with quantitative electromyography (qEMG) and biopsy or genetic verified myopathy and 42 healthy controls were examined with qEMG, MVRC and RAMP, all recorded from the anterior tibial muscle. ResultsThere were significant differences in the motor unit potential (MUP) duration, the early and late supernormalities of the MVRC and the RAMP latencies in myopathy patients compared to controls (p < 0.05 apart from muscle relatively refractory period (MRRP)). When dividing into subgroups, the above-mentioned changes in MVRC and RAMP parameters were increased for the patients with non-inflammatory myopathy, while there were no significant changes in the group of patients with inflammatory myopathy. ConclusionsThe MVRC and RAMP parameters can discriminate between healthy controls and myopathy patients, more significantly for non-inflammatory myopathy. MVRC differences with normal MRRP in myopathy differs from other conditions with membrane depolarisation. SignificanceMVCR and RAMP may have a potential in understanding disease pathophysiology in myopathies. The pathogenesis in non-inflammatory myopathy does not seem to be caused by a depolarisation of the resting membrane potential but rather by the change in sodium channels of the muscle membrane.

A glycine zipper motif is required for the translocation of a T6SS toxic effector into target cells

Type VI secretion systems (T6SSs) can deliver diverse toxic effectors into eukaryotic and bacterial cells. Although much is known about the regulation and assembly of T6SS, the translocation mechanism of effectors into the periplasm and/or cytoplasm of target cells remains elusive. Here, we use the Agrobacterium tumefaciens DNase effector Tde1 to unravel the mechanism of translocation from attacker to prey. We demonstrate that Tde1 binds to its adaptor Tap1 through the N‐terminus, which harbors continuous copies of GxxxG motifs resembling the glycine zipper structure found in proteins involved in the membrane channel formation. Amino acid substitutions on G39xxxG43 motif do not affect Tde1–Tap1 interaction and secretion but abolish its membrane permeability and translocation of its fluorescent fusion protein into prey cells. The data suggest that G39xxxG43 governs the delivery of Tde1 into target cells by permeabilizing the cytoplasmic membrane. Considering the widespread presence of GxxxG motifs in bacterial effectors and pore‐forming toxins, we propose that glycine zipper‐mediated permeabilization is a conserved mechanism used by bacterial effectors for translocation across target cell membranes.