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Objectives: During the early COVID-19 pandemic, college students had to switch to an online learning and online communication environment facing the chances of information overload, misinformation or conflicting information about COVID-19. This study aims to assess the communication needs that have arisen among college students to shed light on the development of a health communication campaign tailored toward college students. Methods: A series of 10 focus group discussions were conducted with 38 total participants. Each group has 2-6 undergraduate or graduate student participants. Nvivo was used to analyze the transcripts. Results: The students reported that they received conflicting information or misinformation. They requested messages with language that was easy to understand with infographics while being culturally appropriate. They advocated for regular and concise email updates from campus leadership. Most participants also preferred COVID-19 control and prevention information on social media. Conclusion: This study revealed the current status and the needs for health information about COVID-19 prevention and control among college students.

The Kir1.1 (ROMK) family of weak inward rectifiers controls K secretion in the renal CCT and K recycling in the renal TALH. A single point mutant of the inward rectifier, F127V-Kir1.1b was used to investigate the K transition between the selectivity filter and the outer mouth of the channel. We hypothesize that normally an aromatic Phe at the external entryway of Kir1.1b facilitates outward K secretion. We tested this by replacing F127-Kir1.1b with a small aliphatic Val . Results indicate that removal of the Phe at 127 suppresses outward currents that normally contribute to K secretion. Results with the F127V mutant could be explained by increased polyamine block and/or a decrease in the avidity of Kir1.1 for K ions near the outer mouth of the channel. The latter is supported by F127V-Kir1.1b having a lower affinity (K m  = 33 mM) for K than wild-type Kir1.1b (K m  = 7 mM) during external K elevation. Conversely, chelation of K with 18-Crown-6 ether reduced K conductance faster in F127V (half-time = 6s) than in wt-Kir1.1b (half-time = 120s), implying that F127V is less hospitable to external K. In other experiments, positive membrane potentials gated the F127V mutant channel closed at physiological levels of external Ca, possibly by electrostatically depleting K adjacent to the membrane, suggesting that the Phe residue is critical for outward K secretion at physiological Ca. We speculate that the avidity of wt-Kir1.1b for external K could result from a cation-Pi interaction between K and the aromatic F127.

Oxygen delivery and tear exchange are considered essential to maintain corneal homoeostasis during contact lens wear. Since the 1940s, fenestrations and back surface channels have been utilised in scleral, corneal rigid, and soft contact lenses in an attempt to enhance corneal oxygen transmission, facilitate the removal of carbon dioxide from the post-lens tear layer, minimise corneal oedema and prevent post-lens tear stagnation. This review examines the use of contact lens fenestrations and channels in both clinical and laboratory settings, and the effect of these modifications upon tear exchange and corneal oedema. Despite almost a century of modifying contact lenses to alter tear dynamics and promote corneal health, the evidence regarding the efficacy of fenestrations and channels is mixed.

Channels are typically gated by several factors, including voltage, ligand and mechanical force. Most members of the calcium homeostasis modulator (CALHM) protein family, large-pore ATP release channels, exist in different oligomeric states. Dynamic conversions between CALHM1 heptamers and octamers to gate the channel were proposed. Meanwhile, the latest study observed that the transient receptor potential vanilloid 3 (TRPV3) channel adopts a dynamic transition between pentamers and canonical tetramers in response to small molecule treatment. These results suggest that oligomeric rearrangement may add a new layer to regulate the channel activities., Competing Interests: Yue Ren, Xue Yang and Yuequan Shen declare that they have no conflict of interest., (© The Author(s) 2024.)

Computational methods such as molecular dynamics (MD) have illuminated how single-atom ions permeate membrane channels and how selectivity among them is achieved. Much less is understood about molecular permeation through eukaryotic channels that mediate the flux of small molecules (e.g. connexins, pannexins, LRRC8s, CALHMs). Here we describe computational methods that have been profitably employed to explore the movements of molecules through wide pores, revealing mechanistic insights, guiding experiments, and suggesting testable hypotheses. This review illustrates MD techniques such as voltage-driven flux, potential of mean force, and mean first-passage-time calculations, as applied to molecular permeation through wide pores. These techniques have enabled detailed and quantitative modeling of molecular interactions and movement of permeants at the atomic level. We highlight novel contributors to the transit of molecules through these wide pathways. In particular, the flexibility and anisotropic nature of permeant molecules, coupled with the dynamics of pore-lining residues, lead to bespoke permeation dynamics. As more eukaryotic large-pore channel structures and functional data become available, these insights and approaches will be important for understanding the physical principles underlying molecular permeation and as guides for experimental design., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

The AvrE family of type III secreted effectors are highly conserved among many agriculturally important phytopathogenic bacteria. Despite their critical roles in the pathogenesis of phytopathogenic bacteria, the molecular functions and virulence mechanisms of these effectors have been largely unknown. However, recent studies have identified host-interacting proteins and demonstrated that AvrE family effectors can form water-permeable channels in the plant plasma membrane (PM) to create a hydrated and nutrient-rich extracellular space (apoplast) required for disease establishment. Here, we summarize these recent discoveries and highlight open questions related to AvrE-targeted host proteins., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pathogenic variants in genes encoding connexins that cause skin diseases, such as keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (HED) or Clouston syndrome, display increased hemichannel activity. Mechanistic insights derived from biophysical studies of the variant connexins support the hypothesis that inhibition of the acquired hemichannel activity could alleviate epidermal pathology. Use of pharmacological blockers and engineered mAbs in mouse models of HED and KID confirm that hemichannel inhibition is a promising target for new therapeutic approaches to KID and HED. Insights from this work could apply to other connexin-based genetic skin diseases in which hemichannel activity is elevated., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The controllable formation of anisotropic gel structures is presently sought for the development of foods with novel textures. Here, we used unidirectional freezing to generate agar gels consisting of a honeycomb-like porous network of elongated and aligned pores. A custom-built Peltier system allowed for control of the freezing front velocity throughout the agar gels. A higher freezing velocity (10 µm/s) led to smaller pore sizes compared to the slower freezing velocity tested (2 µm/s). Texture analysis highlighted the significantly higher Young's modulus in the gels when compressed in the axial vs. radial direction - a direct consequence of the unidirectional freezing. The proton spin-spin relaxation time revealed greater water mobility in the unidirectionally frozen gel with larger pores. This study serves as the basis for the development of anisotropic hydrocolloid gels with a tunable microstructure and texture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Among the various types of polymeric materials, geosynthetics deserve special attention. A geosynthetic is a product made from synthetic polymers that is embedded in soils for various purposes. There are some basic functions of geosynthetics, namely, erosion control, filtration, drainage, separation, reinforcement, containment, barrier, and protection. Geosynthetics for erosion control are very effective in preventing or limiting soil loss by water erosion on slopes or river/channel banks. Where the current line runs through the undercut area of the slope, the curvature of the arch is increased. If this phenomenon is undesirable, the meander arch should be protected from erosion processes. The combination of geosynthetics provides the best resistance to erosion. In addition to external erosion, internal erosion of soils is also a negative phenomenon. Internal erosion refers to any process by which soil particles are eroded from within or beneath a water-retaining structure. Geosynthetics, particularly geotextiles, are used to prevent internal erosion of soils in contact with the filters. Therefore, the main objective of this review paper is to address the many ways in which geosynthetics are used for erosion control (internal and external). Many examples of hydrotechnical and civil engineering applications of geosynthetics will be presented.

Two-pore channels are pathophysiologically important Na + - and Ca 2+ -permeable channels expressed in lysosomes and other acidic organelles. Unlike most other ion channels, their permeability is malleable and ligand-tuned such that when gated by the signaling lipid PI(3,5)P 2 , they are more Na + -selective than when gated by the Ca 2+ mobilizing messenger nicotinic acid adenine dinucleotide phosphate. However, the structural basis that underlies such plasticity and single-channel behavior more generally remains poorly understood. A recent Cryo-electron microscopy (cryo-EM) structure of TPC2 bound to PI(3,5)P 2 in a proposed open-channel conformation provided an opportunity to address this via molecular dynamics (MD) simulation. To our surprise, simulations designed to compute conductance through this structure revealed almost no Na + permeation events even at very high transmembrane voltages. However further MD simulations identified a spontaneous transition to a dramatically different conformation of the selectivity filter that involved expansion and a flip in the orientation of two core asparagine residues. This alternative filter conformation was remarkably stable and allowed Na + to flow through the channel leading to a conductance estimate that was in very good agreement with direct single-channel measurements. Furthermore, this conformation was more permeable for Na + over Ca 2+ . Our results have important ramifications not just for understanding the control of ion selectivity in TPC2 channels but also more broadly in terms of how ion channels discriminate ions., Competing Interests: Competing interests statement:The authors declare no competing interest.

As an alternative to hydrogen peroxide (H 2 O 2 ) production by complex anthraquinone oxidation process, photosynthesis of H 2 O 2 from water and oxygen without sacrificial agents is highly demanded. Herein, a covalently connected molecular heterostructure is synthesized via sequential C-H arylation and Knoevenagel polymerization reactions for visible-light and sacrificial-agent-free H 2 O 2 synthesis. The subsequent copolymerization of the electron-deficient benzodithiophene-4,8-dione (BTD) and the electron-rich biphenyl (B) and p-phenylenediacetonitrile (CN) not only expands the π-conjugated domain but also increases the molecular dipole moment, which largely promotes the separation and transfer of the photoinduced charge carriers. The optimal heterostructured BTDB-CN 0.2 manifested an impressive photocatalytic H 2 O 2 production rate of 1920 μmol g -1  h -1 , which is 2.2 and 11.6 times that of BTDB and BTDCN. As revealed by the femtosecond transient absorption (fs-TA) and theoretical calculations, the linkage serves as a channel for the rapid transfer of photogenerated charge carriers, enhancing the photocatalytic efficiency. Further, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) uncovers that the oxygen reduction reaction occurs through the step one-electron pathway and the mutual conversion between C=O and C-OH with the anchoring of H + during the catalysis favored the formation of H 2 O 2 . This work provides a novel perspective for the design of efficient organic photocatalysts., (© 2024 Wiley-VCH GmbH.)

With the development of deep learning, medical image segmentation in computer-aided diagnosis has become a research hotspot. Recently, UNet and its variants have become the most powerful medical image segmentation methods. However, these methods suffer from (1) insufficient sensing field and insufficient depth; (2) computational nonlinearity and redundancy of channel features; and (3) ignoring the interrelationships among feature channels. These problems lead to poor network segmentation performance and weak generalization ability. Therefore, first of all, we propose an effective replacement scheme of UNet base block, Double residual depthwise atrous convolution (DRDAC) block, to effectively improve the deficiency of receptive field and depth. Secondly, a new linear module, the Multi-scale frequency domain filter (MFDF), is designed to capture global information from the frequency domain. The high order multi-scale relationship is extracted by combining the depthwise atrous separable convolution with the frequency domain filter. Finally, a channel attention called Axial selection channel attention (ASCA) is redesigned to enhance the network's ability to model feature channel interrelationships. Further, we design a novel frequency domain medical image segmentation baseline method FDFUNet based on the above modules. We conduct extensive experiments on five publicly available medical image datasets and demonstrate that the present method has stronger segmentation performance as well as generalization ability compared to other state-of-the-art baseline methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The Fast Health Interoperability Resources (FHIR) standard was proposed and released to solve the interoperability problems of the electronic health records. The FHIR Subscription resources are used to establish real-time event notifications from the FHIR server to another system. There are several communication channels such as rest-hook and websocket. The objective of our work is to compare the performance of the FHIR subscription using the rest-hook and websocket channels., Methods: HAPI FHIR server, python websocket clients and HTTP endpoints were used to measure the processor and memory usage of the two subscription channels. Tests were performed with 5, 10, 15, 20, 30, 40, 50, 60, 70 and 80 clients. The performance was logged using windows performance monitor., Results: The rest-hook subscription showed near six-fold increase in resource utilization when increasing the clients from 5 to 80. On the contrary, the websocket subscription channel did not reach a two-fold increase., Conclusion: The type of the subscription channel should be carefully selected and load distribution should be considered when the number of clients grows.

Outer membrane proteins perform essential functions in uptake and secretion processes in bacteria. MspA is an octameric channel protein in the outer membrane of Mycobacterium smegmatis and is structurally distinct from any other known outer membrane protein. MspA is the founding member of a family with more than 3000 homologs and is one of the most widely used proteins in nanotechnological applications due to its advantageous pore structure and extraordinary stability. While a conserved C-terminal signal sequence is essential for folding and protein assembly in the outer membrane of Gram-negative bacteria, the molecular determinants of these processes are unknown for MspA. In this study, we show that mutation and deletion of methionine 183 in the highly conserved C-terminus of MspA and mutation of the conserved tryptophan 40 lead to a complete loss of protein in heat extracts of M. smegmatis. Swapping these residues partially restores the heat stability of MspA indicating that methionine 183 and tryptophan 40 form a conserved sulfur-π electron interaction, which stabilizes the MspA monomer. Flow cytometry showed that all MspA mutants are surface-accessible demonstrating that oligomerization and membrane integration in M. smegmatis are not affected. Thus, the conserved C-terminus of MspA is essential for its thermal stability, but it is not required for protein assembly in its native membrane, indicating that this process is mediated by a mechanism distinct from that in Gram-negative bacteria. These findings will benefit the rational design of MspA-like pores to tailor their properties in current and future applications., (© 2024 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

This study developed a pore-connected PP-CA membrane by coating cellulose acetate onto a polypropylene filter. A new method was proposed to attach a CA/glycerin coating layer to a porous PP support without a separate binder. The pores of CA and PP were interconnected using a vacuum filtration device. By adding glycerin to the CA chains, the membrane region became more flexible due to glycerin plasticization. Water passed through the membrane under pressure differences, resulting in the formation of interconnected pores between cellulose acetate and polypropylene. The pore size and quantity could be adjusted by varying the molar ratio of glycerin. Fourier transform infrared spectroscopy revealed the interaction between CA and glycerin, while thermogravimetric analysis showed that the membrane's thermal stability increased by approximately 20 °C after vacuum filtration. This simple and cost-effective manufacturing process holds potential for mass-producing separators in the lithium-ion battery industry., Competing Interests: Declaration of competing interest There are no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Channels, tunnels, and pores serve as pathways for the transport of molecules and ions through protein structures, thus participating to their functions. MOLEonline ( https://mole.upol.cz ) is an interactive web-based tool with enhanced capabilities for detecting and characterizing channels, tunnels, and pores within protein structures. MOLEonline has two distinct calculation modes for analysis of channel and tunnels or transmembrane pores. This application gives researchers rich analytical insights into channel detection, structural characterization, and physicochemical properties. ChannelsDB 2.0 ( https://channelsdb2.biodata.ceitec.cz/ ) is a comprehensive database that offers information on the location, geometry, and physicochemical characteristics of tunnels and pores within macromolecular structures deposited in Protein Data Bank and AlphaFill databases. These tunnels are sourced from manual deposition from literature and automatic detection using software tools MOLE and CAVER. MOLEonline and ChannelsDB visualization is powered by the LiteMol Viewer and Mol* viewer, ensuring a user-friendly workspace. This chapter provides an overview of user applications and usage., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Connexins are the proteins that form the gap junction channels that are essential for cell-to-cell communication. These channels are formed by head-to-head docking of hemichannels (each from one of two adjacent cells). Free "undocked" hemichannels at the plasma membrane are mostly closed, although they are still important under physiological conditions. However, abnormal and sustained increase in hemichannel activity due to connexin mutations or acquired conditions can produce or contribute to cell damage. For example, mutations of Cx26, a connexin isoform, can increase hemichannel activity and cause deafness. Studies using purified isolated systems under well-controlled conditions are essential for a full understanding of molecular mechanisms of hemichannel function under normal conditions and in disease, and here, we present methodology for the expression, purification, and functional analysis of hemichannels formed by Cx26., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Amino acids along the conformational motion pathway of the enzyme molecule correlated to its flexibility and rigidity. To enhance the enzyme activity and thermal stability, the motion pathway of Geobacillus stearothermophilus α-amylase has been identified and molecularly modified by using the neural relational inference model and deep learning tool. The significant differences in substrate specificity, enzymatic kinetics, optimal temperature, and thermal stability were observed among the mutants with modified amino acids along the pathway. Mutants especially the P44E demonstrated enhanced hydrolytic activity and catalytic efficiency (k cat /K M ) than the wild-type enzyme to 95.0% and 93.8% respectively, with the optimum temperature increased to 90°C. This mutation from proline to glutamic acid has increased the number and the radius of the bottleneck of the channels, which might facilitate transporting large starch substrates into the enzyme. The mutation could also optimize the hydrogen bonding network of the catalytic center, and diminish the spatial hindering to the substrate entry and exit from the catalytic center., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Hong, Li, Yang, Shen, Wang and Liu.)

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. The main purpose of this review is to show the value of anticipating the effect of baseline treatment of a condition on its comorbidity in order to obtain concomitant positive actions. One of the implications would be that by understanding and targeting shared molecular mechanisms underlying these conditions, it may be possible to tailor drugs that address both simultaneously. To this end, we firstly remind readers of the close link existing between depression and diabetes and secondly address the potential benefit of the pleiotropic actions of two major active molecules used to treat central and peripheral disorders, first a serotonin reuptake inhibitor (Prozac ® ) and then GLP-1R agonists. In the second part, by discussing the therapeutic potential of new experimental antidepressant molecules, we will support the concept that a better understanding of the intracellular signaling pathways targeted by pharmacological agents could lead to future synergistic treatments targeting solely positive effects for comorbidities.

Esterases/lipases from the GDSL family have potential applications in the hydrolysis and synthesis of important esters of pharmaceutical, food, and biotechnical interests. However, the structural and functional understanding of GDSL enzymes is still limited. Here, we report the crystal structure of the GDSL family esterase EstL5 complexed with PMSF at 2.34 Å resolution. Intriguingly, the PMSF binding site is not located at the active site pocket but is situated in a surface cavity. At the active site, we note that there is a trapped crystallization solvent 1,6-hexanediol, which mimics the bound ester chain, allowing for further definition of the active site pocket of EstL5. The most striking structural feature of EstL5 is the presence of a unique channel, which extends approximately 18.9 Å, with a bottleneck radius of 6.8 Å, connecting the active-site pocket and the surface cavity. Replacement of Ser205 with the bulk aromatic residue Trp or Phe could partially block the channel at one end and perturb its access. Reduced enzymatic activity is found in the EstL5 S205W and EstL5 S205F mutants, suggesting the functional relevance of the channel to enzyme catalysis. Our study provides valuable information regarding the properties of the GDSL-family enzymes for designing more efficient and robust biocatalysts.

In the present work, the impact that the longitudinal shape of channels has on the current produced in the flow of a magneto-hydrodynamic microgenerator (MHDMG) is studied. The goal is to find the micro-channel geometry via modeling to maximize the current output for low Reynolds and Mach regimes. To carry out this study, a 3D dynamic numerical tool relying on the finite volume method was handled with the open-source software OpenFOAM. It is the base model to study the impact of intricate geometries on the ability to produce energy. An additional steady-state 2D analytical model was also developed to check some basic modeling assumptions. Both models have been experimentally validated on the simplest flow system having a constant square cross-section throughout. The results produced by both models cross-check very well and compare favorably with respect to experimental data. Hence, using the validated numerical tool, three shapes have been further investigated, namely, progressive (linear decrease of the cross-section), arc (parabolic decrease of the cross-section), and wavy (sinusoidal shape). It was found that the arc channel provides the greatest current output for the same volumetric flow. It is therefore the preferred choice for developing high current gain and more efficient MHDMG used in micro-scaled actuators and sensors., Competing Interests: The authors F. Trillaud, J.E.V. Guzmán, M. Ramírez-Trocherie, and L. Oropeza declare that they have no conflict of interest concerning the development of the work, nor with the information (data, methods, results, etc.) contained in the paper., (© 2023 The Author(s).)

Plants require water and several essential nutrients for their development. The radial transport of nutrients from the soil to the root vasculature is achieved through a combination of three different pathways: apoplastic, symplastic, and transcellular. A common feature for these pathways is the requirement of carriers to transport nutrients across the plasma membrane. An efficient transport of nutrients across the root cell layers relies on a large number of carriers, each of them having their own substrate specificity, tissular and subcellular localization. Polarity is also emerging as a major feature allowing their function. Recent advances on radial transport of nutrients, especially carrier mediated nutrient transport will be discussed in this review, as well as the role of transporters as nutrient sensors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships that may be considered as potential competing interests:Marie Barberon reports financial support was provided by University of Geneva Faculty of Science. Marie Barberon reports a relationship with Swiss National Science Foundation that includes: funding grants., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Calcium (Ca 2+ ) signaling plays a major role in regulating multiple processes in living cells. The photoreceptor potential in Chlamydomonas triggers the generation of all or no flagellar Ca 2+ currents that cause membrane depolarization across the eyespot and flagella. Modulation in membrane potential causes changes in the flagellar waveform, and hence, alters the beating patterns of Chlamydomonas flagella. The rhodopsin-mediated eyespot membrane potential is generated by the photoreceptor Ca 2+ current or P-current however, the flagellar Ca 2+ currents are mediated by unidentified voltage-gated calcium (VGCC or CaV) and potassium channels (VGKC). The voltage-gated ion channel that associates with ChRs to generate Ca 2+ influx across the flagella and its cellular distribution has not yet been identified. Here, we identified putative VGCCs from algae and predicted their novel properties through insilico analysis. We further present experimental evidence on Chlamydomonas reinhardtii VGCCs to predict their novel physiological roles. Our experimental evidences showed that CrVGCC4 localizes to the eyespot and flagella of Chlamydomonas and associates with channelrhodopsins (ChRs). Further in silico interactome analysis of CrVGCCs suggested that they putatively interact with photoreceptor proteins, calcium signaling, and intraflagellar transport components. Expression analysis indicated that these VGCCs and their putative interactors can be perturbed by light stimuli. Collectively, our data suggest that VGCCs in general, and VGCC4 in particular, might be involved in the regulation of the photobehavioral response of Chlamydomonas., Competing Interests: Declaration of competing interest The authors certify that they have nothing to declare in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We address the economic impacts of the role of Biodegradable Fishing Gear (BFG) as a mitigation measure for the ghost fishing impact of lost fishing gear, through scenarios based on industry interviews. We find that the use of BFG is a technical challenge and not an economic problem. The majority of costs to fishermen in terms of BFG use are not related to investment and maintenance costs rather the impact of reduced fishing efficiency. At the Channel static gear fishery level, we estimate the costs of implementing BFG to be as high as £8 million. If the issue of fishing efficiency was resolved (i.e. BFG was a like-for-like) then the large negative costs could be overturned to between a cost of £880,000 and a small positive benefit of around £150,000. Considering the negative environmental impacts of lost gear, the benefits of BFG use over traditional fishing gear would grow exponentially., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Drakeford reports financial support was provided by INTERREG FRANCE-CHANNEL PROGRAMME., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The fruit fly Drosophila melanogaster has provided important insights into how sensory information is transduced by transient receptor potential (TRP) channels in the peripheral nervous system (PNS). However, TRP channels alone have not been able to completely model mechanosensitive transduction in mechanoreceptive chordotonal neurons (CNs). Here, we show that, in addition to TRP channels, the sole voltage-gated sodium channel (Na V ) in Drosophila , Para, is localized to the dendrites of CNs. Para is localized to the distal tip of the dendrites in all CNs, from embryos to adults, and is colocalized with the mechanosensitive TRP channels No mechanoreceptor potential C (NompC) and Inactive/Nanchung (Iav/Nan). Para localization also demarcates spike initiation zones (SIZs) in axons and the dendritic localization of Para is indicative of a likely dendritic SIZ in fly CNs. Para is not present in the dendrites of other peripheral sensory neurons. In both multipolar and bipolar neurons in the PNS, Para is present in a proximal region of the axon, comparable to the axonal initial segment (AIS) in vertebrates, 40-60 μm from the soma in multipolar neurons and 20-40 μm in bipolar neurons. Whole-cell reduction of para expression using RNAi in CNs of the adult Johnston's organ (JO) severely affects sound-evoked potentials (SEPs). However, the duality of Para localization in the CN dendrites and axons identifies a need to develop resources to study compartment-specific roles of proteins that will enable us to better understand Para's role in mechanosensitive transduction., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Ravenscroft et al.)

Mechanosensory feedback of the internal reproductive state drives decisions about when and where to reproduce. 1 For instance, stretch in the Drosophila reproductive tract produced by artificial distention or from accumulated eggs regulates the attraction to acetic acid to ensure optimal oviposition. 2 How such mechanosensory feedback modulates neural circuits to coordinate reproductive behaviors is incompletely understood. We previously identified a stretch-dependent homeostat that regulates egg laying in Caenorhabditis elegans. Sterilized animals lacking eggs show reduced Ca 2+ transient activity in the presynaptic HSN command motoneurons that drive egg-laying behavior, while animals forced to accumulate extra eggs show dramatically increased circuit activity that restores egg laying. 3 Interestingly, genetic ablation or electrical silencing of the HSNs delays, but does not abolish, the onset of egg laying, 3 , 4 , 5 with animals recovering vulval muscle Ca 2+ transient activity upon egg accumulation. 6 Using an acute gonad microinjection technique to mimic changes in pressure and stretch resulting from germline activity and egg accumulation, we find that injection rapidly stimulates Ca 2+ activity in both neurons and muscles of the egg-laying circuit. Injection-induced vulval muscle Ca 2+ activity requires L-type Ca 2+ channels but is independent of presynaptic input. Conversely, injection-induced neural activity is disrupted in mutants lacking the vulval muscles, suggesting "bottom-up" feedback from muscles to neurons. Direct mechanical prodding activates the vulval muscles, suggesting that they are the proximal targets of the stretch-dependent stimulus. Our results show that egg-laying behavior in C. elegans is regulated by a stretch-dependent homeostat that scales postsynaptic muscle responses with egg accumulation in the uterus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Nitrogen (N) is an essential macronutrient for plants and profoundly affects crop yields and qualities. Ammonium (NH 4 + ) and nitrate (NO 3 - ) are major inorganic N forms absorbed by plants from the surrounding environments. Intriguingly, NH 4 + is usually toxic to plants when it serves as the sole or dominant N source. It is thus important for plants to coordinate the utilization of NH 4 + and the alleviation of NH 4 + toxicity. To fully decipher the molecular mechanisms underlying how plants minimize NH 4 + toxicity may broadly benefit agricultural practice. In the current minireview, we attempt to discuss recent discoveries in the strategies for mitigating NH 4 + toxicity in plants, which may provide potential solutions for improving the nitrogen use efficiency (NUE) and stress adaptions in crops., (© 2023 Institute of Botany, Chinese Academy of Sciences.)

Recognizing emotions accurately in real life is crucial in human-computer interaction (HCI) systems. Electroencephalogram (EEG) signals have been extensively employed to identify emotions. The researchers have used several EEG-based emotion identification datasets to validate their proposed models. In this paper, we have employed a novel metaheuristic optimization approach for accurate emotion classification by applying it to select both channel and rhythm of EEG data. In this work, we have proposed the particle swarm with visit table strategy (PS-VTS) metaheuristic technique to improve the effectiveness of EEG-based human emotion identification. First, the EEG signals are denoised using a low pass filter, and then rhythm extraction is done using discrete wavelet transform (DWT). The continuous wavelet transform (CWT) approach transforms each rhythm signal into a rhythm image. The pre-trained MobilNetv2 model has been pre-trained for deep feature extraction, and a support vector machine (SVM) is used to classify the emotions. Two models are developed for optimal channels and rhythm sets. In Model 1, optimal channels are selected separately for each rhythm, and global optima are determined in the optimization process according to the best channel sets of the rhythms. The best rhythms are first determined for each channel, and then the optimal channel-rhythm set is selected in Model 2. Our proposed model obtained an accuracy of 99.2871% and 97.8571% for the classification of HA (high arousal)-LA (low arousal) and HV (high valence)-LV (low valence), respectively with the DEAP dataset. Our generated model obtained the highest classification accuracy compared to the previously reported methods., Competing Interests: Competing InterestsThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The acid-base characteristics of tumor cells and the other elements that compose the tumor microenvironment have been topics of scientific interest in oncological research. There is much evidence confirming that pH conditions are maintained by changes in the patterns of expression of certain proton transporters. In the past decade, the voltage-gated proton channel (Hv1) has been added to this list and is increasingly being recognized as a target with onco-therapeutic potential. The Hv1 channel is key to proton extrusion for maintaining a balanced cytosolic pH. This protein-channel is expressed in a myriad of tissues and cell lineages whose functions vary from producing bioluminescence in dinoflagellates to alkalizing spermatozoa cytoplasm for reproduction, and regulating the respiratory burst for immune system response. It is no wonder that in acidic environments such as the tumor microenvironment, an exacerbated expression and function of this channel has been reported. Indeed, multiple studies have revealed a strong relationship between pH balance, cancer development, and the overexpression of the Hv1 channel, being proposed as a marker for malignancy in cancer. In this review, we present data that supports the idea that the Hv1 channel plays a significant role in cancer by maintaining pH conditions that favor the development of malignancy features in solid tumor models. With the antecedents presented in this bibliographic report, we want to strengthen the idea that the Hv1 proton channel is an excellent therapeutic strategy to counter the development of solid tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alvear-Arias, Pena-Pichicoi, Carrillo, Fernandez, Gonzalez, Garate and Gonzalez.)

The patch-clamp technique represents an electrophysiology type of method. This is one of several insightful approaches with five major configurations, namely a loose patch, cell-attached (also known as on-cell), whole-cell, inside-out, and outside-out modes. The patch-clamp method is more advanced compared to classical electrophysiology since it elucidates single-channel activation in a tiny portion of the membrane in addition to action potential (AP), junction potential (JP), endplate potential (EP), electrical coupling between two adjacent cells via Gap junction hemi-channels, excitatory/inhibitory postsynaptic potentials, and resting membrane potential (RMP). In fact, a malfunction of only one channel or even one component will alter AP amplitude or duration in vitro. If parameters are inferred appropriately and recordings are performed properly, the patch-clamp trace readouts and results are robust. The main hallmarks of currents via voltage-dependent calcium (Cav), hyperpolarization-activated cyclic nucleotide gated non-selective cation (HCN), inwardly rectifying potassium (Kir), voltage-dependent potassium (Kv), and voltage-dependent sodium (Nav) channels are similar and tractable among cells even when they are derived from evolutionary distinct organs and species. However, the size of the membrane area, where the functional subunits reside, and current magnitudes vary among cells of the same type. Therefore, dividing current magnitudes by cell capacitance- current density enables the estimate of functional and active channels relative to recorded cytoplasmic membrane area. Since the patch-clamp recordings can be performed in both current- and voltage-clamp modes, the action potential or spike durations can be adequately elucidated. Sometimes, optical methods are preferred to patch-clamp electrophysiology, but the obtained signals and traces are not robust. Finally, not only an alternans of AP durations, but also that of 'action potential shape' is observed with electrophysiology., Competing Interests: Conflict of interestThe author declares no conflict of interest., (© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2023.)

Background: In 2007 WHO and UNAIDS recommended communication interventions as a key strategy for creating demand for Voluntary Medical Male Circumcision (VMMC) in Southern Africa. In Malawi, VMMC communication interventions, implemented by health communication agencies, have effectively raised awareness of services. However, high awareness of VMMC has not resulted in increased uptake. Consequently, Malawi has achieved the lowest number of circumcisions in Southern Africa., Methods: These researchers carried out a study among the traditionally circumcising Yaos of Mangochi in Southern Region and the non-circumcising Chewas in Central Region. Data were collected using FGDs, KIIs, IDIs, Life Histories and Participatory Rural Appraisal methods. Data were analyzed thematically., Results: This study demonstrates two lessons. First, Laswell's Theory, which has traditionally been used in politics, is relevant to the health sector where the message delivery continuum also needs to be clear on source, message, audience, channel and intended effects. Secondly, according to informants, allowing communities to give feedback to the VMMC messages delivered by health promoters is fundamental. Therefore, failure by Laswell Theory to emphasize on feedback compromises its efficacy. It weakens its ability to foster a common vision between the source and the audience which is prerequisite for behavioral change., Conclusion: The study concluded that community engagement and interpersonal communication which provide room for real-time feedback in any communicative event are the most preferred communication interventions for VMMC services among Yaos and Chewas., (© 2023. The Author(s).)

Due to the unpredictable presence of Non-Cognitive Users (NCUs) in the time and frequency domains, the number of available channels (i.e., channels where no NCUs exist) and corresponding channel indices per Cognitive User (CU) may differ. In this paper, we propose a heuristic channel allocation method referred to as Enhanced Multi-Round Resource Allocation (EMRRA), which employs the asymmetry of available channels in existing MRRA to randomly allocate a CU to a channel in each round. EMRRA is designed to enhance the overall spectral efficiency and fairness of channel allocation. To do this, the available channel with the lowest redundancy is primarily selected upon allocating a channel to a CU. In addition, when there are multiple CUs with the same allocation priority, the CU with the smallest number of available channels is chosen. We execute extensive simulations in order to investigate the effect of the asymmetry of available channels on CUs and compare the performance of EMRRA to that of MRRA. As a result, in addition to the asymmetry of available channels, it is confirmed that most of the channels are simultaneously available to multiple CUs. Furthermore, EMRRA outperforms MRRA in terms of the channel allocation rate, fairness, and drop rate and has a slightly higher collision rate. In particular, EMRRA can remarkably reduce the drop rate compared to MRRA.

In this study, we focused on TRPV1 of African lungfish, Protopterus annectens. During drought at high temperature, African lungfish can survive by undergoing into aestivation in mud cocoons. Therefore, lungfish is considered to have some specialized heat-sensor, TRPV1, for heat tolerance. Further, lungfish which shares similarities with fishes and amphibians, is one of important species for investigating the fish-tetrapod transition. Since fish TRPV1 and tetrapod TRPV1 have some differences, character of lungfish TRPV1 attracts attention. Here, we first cloned TRPV1 paralogue from lungfish, Protopterus annectens (lfTRPV1) and determined the chemical and thermal sensitivities of lfTRPV1 by two-electrode voltage clamp method using frog oocytes. We detected activation of lfTRPV1 by acid and 2-APB, but capsaicin-induced activation was not observed. The sensitivity to acid of lfTRPV1 was similar to that of rat TRPV1 (rTRPV1), but the 2-APB sensitivity of lfTRPV1 was relatively weaker than rTRPV1. Heat stimulation up to 44 °C did not activate lfTRPV1 and the heat-activation was not detected even on acid condition of pH6. This dramatically decreased heat-sensitivity of TRPV1 may contribute the heat tolerance of African lungfish. Moreover, this might be the property of ancient tetrapod-type TRPV1 gene., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This research studies the problem of a joint capacity/capacity reliability analysis of the multiuser multi-input multioutput (MIMO) system functioning in the presence of generalized multipath fading. The study presents the derived results of the closed-form analytical statistical description of the ergodic sum-rate capacity, the capacity reliability and the capacity's higher-order statistics in the case of complex Nakagami-m distributed channel transmission coefficients. A numerical verification of the derived expressions was performed, and it demonstrated excellent correspondence with the simulation. The system performance was evaluated with the help of a numerical analysis of the joint first- and second-order statistics description, depending on the channel and system parameters. The results demonstrated several peculiarities, e.g., the existence of a specific extremum of the capacity reliability for small-sized MIMO systems, its opposite behavior (in terms of the varying number of antenna elements) for heavy and light fading, and the existing asymptotic regions of the system and the channel parameters.

Oxytocin (OT) is a prominent regulator of many aspects of mammalian social behavior and stored in large dense-cored vesicles (LDCVs) in hypothalamic neurons. It is released in response to activity-dependent Ca 2+ influx, but is also dependent on Ca 2+ release from intracellular stores, which primes LDCVs for exocytosis. Despite its importance, critical aspects of the Ca 2+ -dependent mechanisms of its secretion remain to be identified. Here we show that lysosomes surround dendritic LDCVs, and that the direct activation of endolysosomal two-pore channels (TPCs) provides the critical Ca 2+ signals to prime OT release by increasing the releasable LDCV pool without directly stimulating exocytosis. We observed a dramatic reduction in plasma OT levels in TPC knockout mice, and impaired secretion of OT from the hypothalamus demonstrating the importance of priming of neuropeptide vesicles for activity-dependent release. Furthermore, we show that activation of type 1 metabotropic glutamate receptors sustains somatodendritic OT release by recruiting TPCs. The priming effect could be mimicked by a direct application of nicotinic acid adenine dinucleotide phosphate, the endogenous messenger regulating TPCs, or a selective TPC2 agonist, TPC2-A1-N, or blocked by the antagonist Ned-19. Mice lacking TPCs exhibit impaired maternal and social behavior, which is restored by direct OT administration. This study demonstrates an unexpected role for lysosomes and TPCs in controlling neuropeptide secretion, and in regulating social behavior.

Tail-anchored (TA) proteins contain a single C-terminal transmembrane domain (TMD) that is captured by the cytosolic Get3 in yeast (TRC40 in humans). Get3 delivers TA proteins to the Get1/2 complex for insertion into the endoplasmic reticulum (ER) membrane. How Get1/2 mediates insertion of TMDs of TA proteins into the membrane is poorly understood. Using bulk fluorescence and microfluidics assays, we show that Get1/2 forms an aqueous channel in reconstituted bilayers. We estimate the channel diameter to be ∼2.5 nm wide, corresponding to the circumference of two Get1/2 complexes. We find that the Get3 binding can seal the Get1/2 channel, which dynamically opens and closes. Our mutation analysis further shows that the Get1/2 channel activity is required to release TA proteins from Get3 for insertion into the membrane. Hence, we propose that the Get1/2 channel functions as an insertase for insertion of TMDs and as a translocase for translocation of C-terminal hydrophilic segments., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mango ( Mangifera indica ) fruit is known for its taste, health benefits, and drought tolerance. Potassium (K + ) is one of the most abundant ions in a plant cell. It is important for various biological functions related to plant growth, development, and flowering/fruiting. It significantly contributes to fruit yield, quality, and drought tolerance in plants. However, molecular mechanisms comprising K + transport in mango are least known. In the present study, 37 members of K + transport-related genes (PTGs) were identified in mango, which include 22 K + transporters (16 HAKs, 1 HKT, and 6 KEAs) and 15 K + channels (6 TPKs and 8 Shakers). All PTGs were predicted to be expressed at the plasma membrane and possess characteristic motifs and domains. Phylogenetic analysis identified a strong kinship of PTGs among Oryza sativa , Arabidopsis thaliana , Cicer arietinum , Malus domestica , and M. indica . The promoter analysis identified 60 types of cis -elements related to various biological processes. RNA-seq-based expression profiling identified that MiTPK1.2 , MiHAK1 , MiHAK2.1 , HAK6.1 , and MiAKT1.1 were most upregulated in roots and that MiKEA2 , MiAKT2 , and MiAKT1 were upregulated in leaves. Moreover, MiAKT6 , MiHAK1.1 , MiKAT2 , MiKAT2.1 , MiHKT1 , MiTPK1.1 , MiHAK7 , and MiHAK12 were highly expressed during the five growth stages of mango fruit. The current study is the first comprehensive report on K + transport system in tropical fruits. Therefore, it will provide the foundation knowledge for the functional characterization of K + genes in mango and related plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Waqas, Rehman, Rashid, Fiaz, Manzoor and Azeem.)

Selaginella moellendorffii miltiradiene synthase (SmMDS) is a unique bifunctional diterpene synthase (diTPS) that catalyses the successive cyclization of (E,E,E)-geranylgeranyl diphosphate (GGPP) via (+)-copalyl diphosphate (CPP) to miltiradiene, which is a crucial precursor of important medicinal compounds, such as triptolide, ecabet sodium and carnosol. Miltiradiene synthetic processes have been studied in monofunctional diTPSs, while the precise mechanism by which active site amino acids determine product simplicity and the experimental evidence for reaction intermediates remain elusive. In addition, how bifunctional diTPSs work compared to monofunctional enzymes is attractive for detailed research. Here, by mutagenesis studies of SmMDS, we confirmed that pimar-15-en-8-yl + is an intermediate in miltiradiene synthesis. Moreover, we determined the apo-state and the GGPP-bound state crystal structures of SmMDS. By structure analysis and mutagenesis experiments, possible contributions of key residues both in class I and II active sites were suggested. Based on the structural and functional analyses, we confirmed the copal-15-yl + intermediate and unveiled more details of the catalysis process in the SmMDS class I active site. Moreover, the structural and experimental results suggest an internal channel for (+)-CPP produced in the class II active site moving towards the class I active site. Our research is a good example for intermediate identification of diTPSs and provides new insights into the product specificity determinants and intermediate transport, which should greatly facilitate the precise controlled synthesis of various diterpenes., (© 2022 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background and Purpose: Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow. We previously demonstrated that the inhibition of transient receptor potential 6 subfamily C, member 6 (TRPC6) channels facilitate contractile differentiation of VSMCs under ischaemic stress. We here investigated whether TRPC6 inhibition promotes post-ischaemic blood flow recovery through capillary arterialization in vivo., Experimental Approach: Mice were subjected to hindlimb ischaemia by ligating left femoral artery. The recovery rate of peripheral blood flow was calculated by the ratio of ischaemic left leg to non-ischaemic right one. The number and diameter of blood vessels were analysed by immunohistochemistry. Expression and phosphorylation levels of TRPC6 proteins were determined by western blotting and immunohistochemistry., Key Results: Although the post-ischaemic blood flow recovery is reportedly dependent on endothelium-dependent relaxing factors, systemic TRPC6 deletion significantly promoted blood flow recovery under the condition that nitric oxide or prostacyclin production were inhibited, accompanying capillary arterialization. Cilostazol, a clinically approved drug for peripheral arterial disease, facilitates blood flow recovery by inactivating TRPC6 via phosphorylation at Thr69 in VSMCs. Furthermore, inhibition of TRPC6 channel activity by pyrazole-2 (Pyr2; BTP2; YM-58483) promoted post-ischaemic blood flow recovery in Apolipoprotein E-knockout mice., Conclusion and Implications: Suppression of TRPC6 channel activity in VSMCs could be a new strategy for the improvement of post-ischaemic peripheral blood circulation., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Microbial rhodopsins are photoreceptive membrane proteins found from diverse microorganisms such as archaea, eubacteria, eukaryotes and viruses. Many microbial rhodopsins possess ion-transport activity by light, such as channels and pumps, and ion-transporting rhodopsins are important tools in optogenetics that control animal behavior by light. Historically, molecular mechanism of rhodopsins has been studied by spectroscopic methods for purified proteins. On the other hand, ion-transport function has to be studied by different methods. This chapter introduces two methods of functional assay of ion-transporting rhodopsins by light. One is a patch clamp method using mammalian cells, and another is an ion-transport assay using pH electrode and microbial cells. These functional assay provides fundamental data of ion-transporting rhodopsins, and thus contributes to evaluation for optogenetic tools., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na + /K + -ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Dong, Zhang, Shu, Tu and Yao.)

The pathogenesis of ventricular tachycardia (VT) in most patients with a prior myocardial scarring is reentry involving compartmentalized muscle fibers protected within the scar. Often the 12-lead ECG morphology of the VT itself is not available when treated with a defibrillator. Consequently, VT ablation takes on an interesting challenge of finding critical targets in sinus rhythm. High-density recordings are essential to evaluate a substrate based on whole electrogram voltage and activation delay, supplemented with substrate perturbation through alternate site pacing or introducing an extra stimulation. In this article, we discuss contemporary intracardiac electrogram targets for VT ablation, with explanation on each of their specific fundamental physiology., Competing Interests: Disclosure Dr S. Nayyar is examining voltage and time-domain mapping strategy for ventricular tachycardia ablation and is the principal investigator of Target- VT study (URL: www.ANZCTR.org.au. Unique identifier: ACTRN12620000049976). Dr S. Nayyar reports no relationships with industry. All figures included in this article are from Authors prior published and unpublished works., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

A novel approach for multichannel epilepsy seizure classification which will help to automatically locate seizure activity present in the focal brain region was proposed. This paper suggested an Internet of Things (IoT) framework based on a smart phone by utilizing a novel feature termed multiresolution critical spectral verge (MCSV), based on frequency-derived information for epileptic seizure classification which was optimized using a flower pollination algorithm (FPA). A wireless sensor technology (WSN) was utilized to record the electroencephalography (EEG) signal of epileptic patients. Next, the EEG signal was pre-processed utilizing a multiresolution-based adaptive filtering (MRAF) method. Then, the maximal frequency point at which the power spectral density (PSD) of each EEG segment was greater than the average spectral power of the corresponding frequency band was computed. This point was further optimized to extract a point termed as critical spectral verge (CSV) to extract the exact high frequency oscillations representing the actual seizure activity present in the EEG signal. Next, a support vector machine (SVM) classifier was used for channel-wise classification of the seizure and non-seizure regions using CSV as a feature. This process of classification using the CSV feature extracted from the MRAF output is referred to as the MCSV approach. As a final step, cloud-based services were employed to analyze the EEG information from the subject's smart phone. An exhaustive analysis was undertaken to assess the performance of the MCSV approach for two datasets. The presented approach showed an improved performance with a 93.83% average sensitivity, a 97.94% average specificity, a 97.38% average accuracy with the SVM classifier, and a 95.89% average detection rate as compared with other state-of-the-art studies such as deep learning. The methods presented in the literature were unable to precisely localize the origination of the seizure activity in the brain region and reported a low seizure detection rate. This work introduced an optimized CSV feature which was effectively used for multichannel seizure classification and localization of seizure origination. The proposed MCSV approach will help diagnose epileptic behavior from multichannel EEG signals which will be extremely useful for neuro-experts to analyze seizure details from different regions of the brain.

Protein tunnels are essential in transporting small molecules into the active sites of enzymes. Tunnels' geometrical and physico-chemical properties influence the transport process. The tunnels are attractive hot spots for protein engineering and drug development. However, studying the ligand binding and unbinding using experimental techniques is challenging, while in silico methods come with their limitations, especially in the case of resource-demanding virtual screening pipelines. Caver Web 1.2 is a new version of the web server combining the capabilities for the detection of protein tunnels with the calculation of the ligand trajectories. The new version of the Caver Web server was expanded with the ability to fetch novel ligands from the Integrated Database of Small Molecules and with the fully automated virtual screening pipeline allowing for the fast evaluation of the predefined set of over 4,300 currently approved drugs. The virtual screening pipeline is accompanied by a comprehensive user interface, making it a viable service for the broader spectrum of companies and the academic user community. The web server is freely available for academic use at https://loschmidt.chemi.muni.cz/caverweb., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: SARS-CoV-2 has undergone mutations, yielding clinically relevant variants., Hypothesis: We hypothesized that in SARS-CoV-2, two highly conserved Orf3a and E channels directly related to the virus replication were a target for the detection and inhibition of the viral replication, independent of the variant, using FDA-approved ion channel modulators., Methods: A combination of a fluorescence potassium ion assay with channel modulators was developed to detect SARS-CoV-2 Orf3a/E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant), which are ion channel blockers, were tested as to whether they inhibited Orf3a/E channel activity in isolated virus variants and in nasal swab samples from COVID-19 patients. The variants were confirmed by PCR sequencing., Results: In isolated SARS-CoV-2 Alpha, Beta, and Delta variants, the channel activity of Orf3a/E was detected and inhibited by emodin and gliclazide (IC 50 = 0.42 mM). In the Delta swab samples, amitriptyline and amantadine inhibited the channel activity of viral proteins, with IC 50 values of 0.73 mM and 1.11 mM, respectively. In the Omicron swab samples, amitriptyline inhibited the channel activity, with an IC 50 of 0.76 mM., Conclusions: We developed an efficient method to screen FDA-approved ion channel modulators that could be repurposed to detect and inhibit SARS-CoV-2 viral replication, independent of variants.

The exponential growth of the edge-based Internet-of-Things (IoT) services and its ecosystems has recently led to a new type of communication network, the Low Power Wide Area Network (LPWAN). This standard enables low-power, long-range, and low-data-rate communications. Long Range Wide Area Network (LoRaWAN) is a recent standard of LPWAN that incorporates LoRa wireless into a networked infrastructure. Consequently, the consumption of smart End Devices (EDs) is a major challenge due to the highly dense network environment characterised by limited battery life, spectrum coverage, and data collisions. Intelligent and efficient service provisioning is an urgent need of a network to streamline the networks and solve these problems. This paper proposes a Dynamic Reinforcement Learning Resource Allocation (DRLRA) approach to allocate efficient resources such as channel, Spreading Factor (SF), and Transmit Power (Tp) to EDs that ultimately improve the performance in terms of consumption and reliability. The proposed model is extensively simulated and evaluated with the currently implemented algorithms such as Adaptive Data Rate (ADR) and Adaptive Priority-aware Resource Allocation (APRA) using standard and advanced evaluation metrics. The proposed work is properly cross validated to show completely unbiased results.

Acceleration of chemical reactions by the enzymes optimized using protein engineering represents one of the key pillars of the contribution of biotechnology towards sustainability. Tunnels and channels of enzymes with buried active sites enable the exchange of ligands, ions, and water molecules between the outer environment and active site pockets. The efficient exchange of ligands is a fundamental process of biocatalysis. Therefore, enzymes have evolved a wide range of mechanisms for repetitive conformational changes that enable periodic opening and closing. Protein-ligand interactions are traditionally studied by molecular docking, whereas molecular dynamics is the method of choice for studying conformational changes and ligand transport. However, computational demands make molecular dynamics impractical for screening purposes. Thus, several approximative methods have been recently developed to study interactions between a protein and ligand during the ligand transport process. Apart from identifying the best binding modes, these methods also provide information on the energetics of the transport and identify problematic regions limiting the ligand passage. These methods use approximations to simulate binding or unbinding events rapidly (calculation times from minutes to hours) and provide energy profiles that can be used to rank ligands or pathways. Here we provide a critical comparison of available methods, showcase their results on sample systems, discuss their practical applications in molecular biotechnologies and outline possible future developments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

We investigated the effect of the acetylcholine muscarinic receptor inhibitor benztropine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Benztropine inhibited Kv currents in a concentration-dependent manner, with an apparent IC50 value of 6.11 ± 0.80 μM and Hill coefficient of 0.62 ± 0.03. Benztropine shifted the steady-state activation curves toward a more positive potential, and the steady-state inactivation curves toward a more negative potential, suggesting that benztropine inhibited Kv channels by affecting the channel voltage sensor. Train pulse (1 or 2 Hz)-induced Kv currents were effectively reduced by the benztropine treatment. Furthermore, recovery time constants of Kv current inactivation increased significantly in response to benztropine. These results suggest that benztropine inhibited vascular Kv channels in a use (state)-dependent manner. The inhibitory effect of benztropine was canceled by pretreatment with the Kv 1.5 inhibitor, but there was no obvious change after pretreatment with Kv 2.1 or Kv7 inhibitors. In conclusion, benztropine inhibited the Kv current in a concentration- and use (state)-dependent manner. Inhibition of the Kv channels by benztropine primarily involved the Kv1.5 subtype. Restrictions are required when using benztropine to patients with vascular disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aquaporins (AQPs) are a family of small transmembrane proteins that selectively transport water and other small molecules and ions following an osmotic gradient across cell plasma membranes. This enables them to regulate numerous functions including water homeostasis, fat metabolism, proliferation, migration, and adhesion. Previous structural and functional studies highlight a strong biological relationship between AQP protein expression, localization, and key biological functions in normal and cancer tissues, where aberrant AQP expression correlates with tumorigenesis and metastasis. In this review, we discuss the roles of AQP1, AQP3, AQP4, AQP5, and AQP7 in breast cancer progression and metastasis, including the role of AQPs in the tumor microenvironment, to highlight potential contributions of stromal-derived to epithelial-derived AQPs to breast cancer. Emerging evidence identifies AQPs as predictors of response to cancer therapy and as targets for increasing their sensitivity to treatment. However, these studies have not evaluated the requirements for protein structure on AQP function within the context of breast cancer. We also examine how AQPs contribute to a patient's response to cancer treatment, existing AQP inhibitors and how AQPs could serve as novel predictive biomarkers of therapy response in breast cancer. Future studies also should evaluate AQP redundancy and compensation as mechanisms used to overcome aberrant AQP function. This review highlights the need for additional research into how AQPs contribute molecularly to therapeutic resistance and by altering the tumor microenvironment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Charlestin, Fulkerson, Arias Matus, Walker, Carthy and Littlepage.)