hv1

Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times...

In this study, microstructural characterization, mechanical (tensile and compressive) properties, and tribological (wear) properties of Titanium Grade 5 alloy after the oxidation process were examined. While it is observed that the grey contrast coloured α grains are coaxial in the microstructures, it is seen that there are black contrast coloured β grains at the grain boundaries. However, in oxidised Titanium Grade 5, it is possible to observe that the α structure becomes larger, and the number and density of the structure increases...

Titanium alloys are widely used in various structural materials due to their lightweight properties. However, the low wear resistance causes significant economic losses every year. Therefore, it is necessary to implement wear-resistant protection on the surface of titanium alloys. In this study, four types of in situ composite ceramic coatings with two-layer gradient structures were prepared on a Ti-6Al-4V (TC4) substrate using laser cladding. In order to reduce the dilution rate, a transition layer (Ti-40SiC (vol...

The majority of voltage-gated ion channels contain a defined voltage-sensing domain and a pore domain composed of highly conserved amino acid residues that confer electrical excitability via electromechanical coupling. In this sense, the voltage-gated proton channel (Hv1) is a unique protein in that voltage-sensing, proton permeation and pH-dependent modulation involve the same structural region. In fact, these processes synergistically work in concert, and it is difficult to separate them. To investigate the process of Hv1 voltage sensor trapping, we follow voltage-sensor movements directly by leveraging mutations that enable the measurement of Hv1 channel gating currents...

In this work, we propose a methodology based on Monte Carlo Markov chains to explore the parameter space of kinetic models for ion channels. The methodology allows the detection of potential parameter sets of a model that are compatible with experimentally obtained whole-cell currents, which could remain hidden when methods focus on obtaining the parameters that provide the best fit. To show its implementation and utility, we considered a four-state kinetic model proposed in the literature to describe the activation of the voltage-gated proton channel (Hv1), Biophysical Journal, 2014 , 107 , 1564...

BACKGROUND: Endothelial dysfunction and impaired oxygenation of the heart is a hallmark of several diseases, including coronary artery disease, hypertension, diabetes, and sleep apnea. Recent studies indicate that oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) imaging combined with breathing maneuvers may allow for assessing coronary vascular responsiveness as a marker for coronary vascular function in various clinical settings. However, despite the use of OS-CMR in evaluating tissue oxygenation, the reproducibility of these standardized, combined breathing maneuvers as a vasoactive stimulus has yet to be systematically assessed or validated...

A growing body of evidence highlights the crucial role of metabolic reprogramming in activated immune cells, significantly contributing to both the initiation and progression of neuroinflammation and neurodegenerative diseases. The voltage-gated H channel (Hv1) has been reported to be involved in microglial activation and acts as a key driver of neuroinflammation. This study aimed to explore how Hv1-mediated metabolic reprogramming contributes to neuroinflammation and to assess the therapeutic potential of the Hv1 inhibitor 2-GBI in a model of lipopolysaccharide (LPS)-induced neuroinflammation...

In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process...

The voltage-sensing domain (VSD) is a module capable of responding to changes in the membrane potential through conformational changes and facilitating electromechanical coupling to open a pore gate, activate proton permeation pathways, or promote enzymatic activity in some membrane-anchored phosphatases. To carry out these functions, this module acts cooperatively through conformational changes. The VSD is formed by four transmembrane segments (S1-S4) but the S4 segment is critical since it carries positively charged residues, mainly Arg or Lys, which require an aqueous environment for its proper function...

Voltage-gated proton channels (Hv1) are important regulators of the immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice and have been proposed as a potential therapeutic target to alleviate dysregulated immunosuppression in tumors. However, till date, there is a lack of evidence regarding the functioning of the Hvcn1 and reports on mHv1 isoform diversity in mice and MDSCs. A computational prediction has suggested that the Hvcn1 gene may express up to six transcript variants, three of which are translated into distinct N-terminal isoforms of mHv1: mHv1...

The membrane potential of a cell (Vm ) regulates several physiological processes. The voltage sensor domain (VSD) is a region that confers voltage sensitivity to different types of transmembrane proteins such as the following: voltage-gated ion channels, the voltage-sensing phosphatase (Ci-VSP), and the sperm-specific Na+ /H+ exchanger (sNHE). VSDs contain four transmembrane segments (S1-S4) and several positively charged amino acids in S4, which are essential for the voltage sensitivity of the protein. Generally, in response to changes of the Vm , the positive residues of S4 displace along the plasma membrane without generating ionic currents through this domain...

The voltage-gated proton channel (Hv1) plays an essential role in numerous biological processes, but a detailed molecular understanding of its function is lacking. The lack of reliable structures for the open and resting states is a major handicap. Several models have been built based on homologous voltage sensors and the structure of a chimera between the mouse homologue and a phosphatase voltage sensor, but their validity is uncertain. In addition, differing views exist regarding the mode of proton translocation, the role of specific residues, and the mechanism of pH effects on voltage gating...

Approximately 20-68% of traumatic brain injury (TBI) patients exhibit trauma-associated olfactory deficits (OD) which can compromise not only the quality of life but also cognitive and neuropsychiatric functions. However, few studies to date have examined the impact of experimental TBI on OD. The present study examined inflammation and neuronal dysfunction in the olfactory bulb (OB) and the underlying mechanisms associated with OD in male mice using a controlled cortical impact (CCI) model. TBI caused a rapid inflammatory response in the OB as early as 24 h post-injury, including elevated mRNA levels of proinflammatory cytokines, increased numbers of microglia and infiltrating myeloid cells, and increased IL1β and IL6 production in these cells...

ATP is an important molecule implicated in diverse biochemical processes, including the modulation of ion channel and transporter activity. The voltage-gated proton channel (Hv1) controls proton flow through the transmembrane pathway in response to membrane potential, and various molecules regulate its activity. Although it is believed that ATP is not essential for Hv1 activity, a report has indicated that cytosolic ATP may modulate Hv1. However, the detailed molecular mechanism underlying the effect of ATP on Hv1 is unknown, and whether ATP is involved in the physiological regulation of Hv1 activity remains unclear...

Spinal cord injury (SCI) causes severe functional deficits and neuronal damage, accompanied by intense glial activation. The voltage-gated proton channel Hv1, selectively expressed on microglia, is associated with SCI progression. However, the effect of Hv1 on the phenotypes and functions of reactive astrocytes after SCI remains unclear. Here, we combined Hv1 knockout (Hv1-/- ) mice and T10 spinal cord contusion to investigate the effects of microglial Hv1 on SCI pathophysiology and the phenotypes and functions of reactive astrocytes...

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca2+ and K+ . Moreover, the voltage-gated proton channel Hv1, the sperm-specific sodium-hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature-sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum...

The austenitic 316L stainless steel (SS) is used extensively for marine applications as well as in construction, processing, and petrochemical industries due to its outstanding corrosion resistance properties. This study investigates the density, microhardness, and microstructural development of 316L SS samples fabricated by selective laser melting (SLM) under high laser energy densities. The selective laser melted (SLMed) specimens were fabricated under high laser energy densities (500, 400, and 333.33 J/mm3 ) and their metallurgical and mechanical properties were compared with the wrought specimen...

Bubaline alphaherpesvirus 1 (BuHV-1) is a pathogen of water buffaloes responsible for economic loss worldwide. MicroRNAs (miRNAs) regulate gene expression produced by alphaherpesviruses and hosts. This study aimed at (a) unravelling the ability of BuHV-1 to produce miRNAs, including hv1-miR-B6, hv1-miR-B8, hv1-miR-B9; (b) measuring the host immune-related miRNAs associated to herpesvirus infection, including miR-210-3p, miR-490-3p, miR-17-5p, miR-148a-3p, miR-338-3p, miR-370-3p, by RT-qPCR; (c) identifying candidate markers of infection by receiver-operating characteristic (ROC) curves; (d) exploiting the biological functions by pathway enrichment analyses...

Bioimplants should meet important surface integrity criteria, with the main goal of the manufacturing process to improve wear and corrosion resistance properties. This requires a special approach at the cutting stage. During this research, the impact of the cutting parameters on improving the surface integrity of AISI 316L steel was evaluated. In this context of bioimplant applications, the mean roughness Sa value was obtained in the range of 0.73-4.19 μm. On the basis of the results obtained, a significant effect was observed of both the cutting speed and the feed rate on changes in the microstructure of the near-surface layer...

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...