Explore the vast range of titles available.

Calcium (Ca 2+ )-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca 2+ -activated chloride channel that is activated by intracellular Ca 2+ and Ca 2+ -mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca 2+ -activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca 2+ -activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca 2+ -activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes. TMEM16A (anoctamin 1) as a calcium-activated channel Calcium-activated chloride channels play a fundamental role in many physiological processes, but their molecular identity has so far evaded characterization. This paper shows that the transmembrane protein TMEM16A, also known as anoctamin 1 or ANO1, is a Ca 2+ -activated chloride channel. TMEM16A has a novel trimeric structure composed of eight transmembrane domains, very different from all previously characterized ionic channels. Its knock-down reduced native Ca 2+ activated chloride currents and impairs salivary secretion in mice.

Benign prostatic hyperplasia (BPH) is characterized by an enlargement of the prostate, causing lower urinary tract symptoms in elderly men worldwide. However, the molecular mechanism underlying the pathogenesis of BPH is unclear. Anoctamin1 (ANO1) encodes a Ca2+-activated chloride channel (CaCC) that mediates various physiological functions. Here, we demonstrate that it is essential for testosterone-induced BPH. ANO1 was highly amplified in dihydrotestosterone (DHT)-treated prostate epithelial cells, whereas the selective knockdown of ANO1 inhibited DHT-induced cell proliferation. Three androgen-response elements were found in the ANO1 promoter region, which is relevant for the DHT-dependent induction of ANO1. Administration of the ANO1 blocker orAno1small interfering RNA, inhibited prostate enlargement and reduced histological abnormalities in vivo. We therefore concluded that ANO1 is essential for the development of prostate hyperplasia and is a potential target for the treatment of BPH.

Background: Various pathological conditions such as inflammation or injury can evoke pain hypersensitivity. That represents the response to innocuous stimuli or exaggerated response to noxious stimuli. The molecular mechanism based on the pain hypersensitivity is associated with changes in many of ion channels in dorsal-root ganglion (DRG) neurons. Anoctamin 1 (ANO1/TMEM16A), a Ca2+ activated chloride channel is highly visible in small DRG neurons and responds to heat. Mice with an abolished function of ANO1 in DRG neurons demonstrated attenuated pain-like behaviors when exposed to noxious heat, suggesting a role in acute thermal nociception. In this study, we further examined the function of ANO1 in mediating inflammation- or injury-induced hyperalgesia or allodynia. Results: Using Advillin/Ano1fl/fl (Adv/Ano1fl/fl) mice that have a functional ablation of Ano1 mainly in DRG neurons, we were able to determine its role in mediating thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury. The thermal hyperalgesia and mechanical allodynia induced by carrageenan injection and spared-nerve injury were significantly reduced in Adv/Ano1fl/fl mice. In addition, flinching or licking behavior after bradykinin or formalin injection was also significantly reduced in Adv/Ano1fl/fl mice. Since pathological conditions augment nociceptive behaviors, we expected ANO1's contribution to the excitability of DRG neurons. Indeed, the application of inflammatory mediators reduced the threshold for action potential (rheobase) or time for induction of the first action potential in DRG neurons isolated from control (Ano1fl/fl) mice. These parameters for neuronal excitability induced by inflammatory mediators were not changed in Adv/Ano1fl/fl mice, suggesting an active contribution of ANO1 in augmenting the neuronal excitability. Conclusions: In addition to ANO1's role in mediating acute thermal pain as a heat sensor, ANO1 is also capable of augmenting the excitability of DRG neurons under inflammatory or neuropathic conditions and thereby aggravates inflammation- or tissue injury-induced pathological pain.

Calcium-activated chloride channels (CaCCs) mediate numerous physiological functions and are best known for the transport of electrolytes and water in epithelia. In the intestine, CaCC currents are considered necessary for the secretion of fluid to protect the intestinal epithelium. Although genetic ablation of ANO1/TMEM16A, a gene encoding a CaCC, reduces the carbachol-induced secretion of intestinal fluid, its mechanism of action is still unknown. Here, we confirm that ANO1 is essential for the secretion of intestinal fluid. Carbachol-induced transepithelial currents were reduced in the proximal colon of Ano1- deficient mice. Surprisingly, cholera toxin-induced and cAMP-induced fluid secretion, believed to be mediated by CFTR, were also significantly reduced in the intestine of Ano1 -deficient mice. ANO1 is largely expressed in the apical membranes of intestines, as predicted for CaCCs. The Ano1 -deficient colons became edematous under basal conditions and had a greater susceptibility to dextran sodium sulfate-induced colitis. However, Ano1 depletion failed to affect tumor development in a model of colorectal cancer. We thus conclude that ANO1 is necessary for cAMP- and carbachol-induced Cl − secretion in the intestine, which is essential for the protection of the intestinal epithelium from colitis. Colitis: Intestinal membrane protein implicated in defective fluid secretion An ion channel, a membrane protein allowing ion transport, that controls the flow of chloride is needed for proper secretion of protective fluids in the intestine. Uhtaek Oh from the Korea Institute of Science & Technology in Seoul, South Korea, and colleagues showed that cells lining the intestinal surface express a calcium-activated chloride channel called anoctamin-1 (ANO1) that regulates fluid secretion in the gut. Compared to control animals, ANO1-deficient mice released less fluid into their intestines following exposure to a diarrhea-inducing toxin or to a chloride transport–stimulating signaling molecule. This fluid secretion was previously thought to be mediated via a different ion channel. The ANO1-deficient mice accumulated fluid within colonic tissues, which increased their susceptibility to colitis. The findings point to ANO1 activation as a potential therapeutic strategy for treating colitis.

This review focuses on deepening the structural understanding of crack-based strain sensors (CBSS) on stretchable and flexible polymeric substrates and promoting sensor performance optimization. CBSS are cutting-edge devices that purposely incorporate cracks into their functional elements, thereby achieving high sensitivity, wide working ranges, and rapid response times. To optimize the performance of CBSS, systematic research on the structural characteristics of cracks is essential. This review comprehensively analyzes the key factors determining CBSS performance such as the crack mechanism, geometrical factors, and functional structures and proposes optimization strategies grounded in these insights. In addition, we explore the potential of numerical analysis and machine learning to offer novel perspectives for sensor optimization. Following this, we introduce various applications of CBSS. Finally, we discuss the current challenges and future prospects in CBSS research, providing a roadmap for next-generation technologies.

Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.

The patterning of electrospun fibers is a key technology applicable to various fields. This study reports a novel focused patterning method for electrospun nanofibers that uses a cylindrical dielectric guide. The finite elements method (FEM) was used to analyze the electric field focusing phenomenon and ground its explanation in established theory. The horizontal and vertical electric field strengths in the simulation are shown to be key factors in determining the spatial distribution of nanofibers. The experimental results demonstrate a relationship between the size of the cylindrical dielectric guide and that of the electrospun area accumulated in the collector. By concentrating the electric field, we were able to fabricate a pattern of less than 6 mm. The demonstration of continuous line and square patterning shows that the electrospun area can be well controlled. This novel patterning method can be used in a variety of applications, such as sensors, biomedical devices, batteries, and composites.

Biology is characterized by smooth, elastic, and nonplanar surfaces; as a consequence, soft electronics that enable interfacing with nonplanar surfaces allow applications that could not be achieved with the rigid and integrated circuits that exist today. Here, we review the latest examples of technologies and methods that can replace elasticity through a structural approach; these approaches can modify mechanical properties, thereby improving performance, while maintaining the existing material integrity. Furthermore, an overview of the recent progress in wave/wrinkle, stretchable interconnect, origami/kirigami, crack, nano/micro, and textile structures is provided. Finally, potential applications and expected developments in soft electronics are discussed.

TRPM2 a cation channel is also known to work as an enzyme that hydrolyzes highly reactive, neurotoxic ADP-ribose (ADPR). Although ADPR is hydrolyzed by NUT9 pyrophosphatase in major organs, the enzyme is defective in the brain. The present study questions the role of TRPM2 in the catabolism of ADPR in the brain. Genetic ablation of Trpm2 results in the disruption of ADPR catabolism that leads to the accumulation of ADPR and reduction in AMP. Trpm2 −/− mice elicit the reduction in autophagosome formation in the hippocampus. Trpm2 −/− mice also show aggregations of proteins in the hippocampus, aberrant structural changes and neuronal connections in synapses, and neuronal degeneration. Trpm2 −/− mice exhibit learning and memory impairment, enhanced neuronal intrinsic excitability, and imbalanced synaptic transmission. These results respond to long-unanswered questions regarding the potential role of the enzymatic function of TRPM2 in the brain, whose dysfunction evokes protein aggregation. In addition, the present finding answers to the conflicting reports such as neuroprotective or neurodegenerative phenotypes observed in Trpm2 −/− mice.

Rail temperature is the main effector of train operation. High rail temperature induces rail deformation and because of limited space for rail deformation, rails are under compressive pressure. When rail deformation is exceeded, rail buckling occurs, and this causes rail derailment. Although such a rail derailment is infrequent, the casualties of human lives and properties are catastrophic. To prevent this, the rail industry has been monitoring rail temperature. However, existing representative rail temperature measurement points (RMPs) are selected without considering thermal deformation, and there is no sufficient information for selecting RMPs. In this study, we suggest a novel advanced RMP (ARMP) considering rail installation orientation and meteorological conditions. We designed a measurement system for rail temperature and obtained 1-year data of rail temperature at multiple internal, external rail points and the surrounding environments. We validated our measured data with field data similar to the climate in which the measurement system was installed. The maximum error and Mean Absolute Error (MAE) were 3.3 °C and 0.97 °C respectively. We calculated average deformation points (ADPs) and analyzed them with respect to the energy that the rail receives from the meteorological conditions, which are represented by the cumulative amount of solar irradiance and installation orientation. Based on the tendency of ADPs, we suggested a simple equation of ARMP with only one variable, month. ARMP showed high accuracy in measuring rail temperature at two installation orientations than previous RMPs (R-square: 0.9255, 0.8577 and MAE: 0.21 °C, 0.33 °C). We expect that this study would contribute to efficient train operation for the precise measurement of rail temperature.