scholarly journals Distinct roles for innexin gap junctions and hemichannels in mechanosensation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Denise S Walker ◽  
William R Schafer

Mechanosensation is central to a wide range of functions, including tactile and pain perception, hearing, proprioception, and control of blood pressure, but identifying the molecules underlying mechanotransduction has proved challenging. In Caenorhabditis elegans, the avoidance response to gentle body touch is mediated by six touch receptor neurons (TRNs), and is dependent on MEC-4, a DEG/ENaC channel. We show that hemichannels containing the innexin protein UNC-7 are also essential for gentle touch in the TRNs, as well as harsh touch in both the TRNs and the PVD nociceptors. UNC-7 and MEC-4 do not colocalize, suggesting that their roles in mechanosensory transduction are independent. Heterologous expression of unc-7 in touch-insensitive chemosensory neurons confers ectopic touch sensitivity, indicating a specific role for UNC-7 hemichannels in mechanosensation. The unc-7 touch defect can be rescued by the homologous mouse gene Panx1 gene, thus, innexin/pannexin proteins may play broadly conserved roles in neuronal mechanotransduction.

2019 ◽  
Author(s):  
Denise S. Walker ◽  
William R. Schafer

AbstractMechanosensation is central to a wide range of functions, including tactile and pain perception, hearing, proprioception, and control of blood pressure, but identifying the molecules underlying mechanotransduction has proved challenging. In Caenorhabditis elegans, the avoidance response to gentle body touch is mediated by 6 touch receptor neurons (TRNs), and is dependent on MEC-4, a DEG/ENaC channel. We show that hemichannels containing the innexin protein UNC-7 are also essential for gentle touch in the TRNs, as well as harsh touch in both the TRNs and the PVD nociceptors. UNC-7 and MEC-4 do not colocalize, suggesting that their roles in mechanosensory transduction are independent. Heterologous expression of unc-7 in touch-insensitive chemosensory neurons confers ectopic touch sensitivity, indicating a direct role for UNC-7 hemichannels in mechanosensation. The unc-7 touch defect can be rescued by the homologous mouse gene Panx1 gene, thus, innexin/pannexin proteins may play broadly conserved roles in neuronal mechanotransduction.


2015 ◽  
Vol 5 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Xiaoyin Chen ◽  
Margarete Diaz Cuadros ◽  
Martin Chalfie

Abstract Caenorhabditis elegans senses gentle touch along the body via six touch receptor neurons. Although genetic screens and microarray analyses have identified several genes needed for touch sensitivity, these methods miss pleiotropic genes that are essential for the viability, movement, or fertility of the animals. We used neuronally enhanced feeding RNA interference to screen genes that cause lethality or paralysis when mutated, and we identified 61 such genes affecting touch sensitivity, including five positive controls. We confirmed 18 genes by using available alleles, and further studied one of them, tag-170, now renamed txdc-9. txdc-9 preferentially affects anterior touch response but is needed for tubulin acetylation and microtubule formation in both the anterior and posterior touch receptor neurons. Our results indicate that neuronally enhanced feeding RNA interference screens complement traditional mutageneses by identifying additional nonviable genes needed for specific neuronal functions.


2021 ◽  
Vol 273 ◽  
pp. 08018
Author(s):  
Sergey Zyryanov ◽  
Anastasia Kalmykova ◽  
Tatyana Levonenkova ◽  
Ekaterina Kozlova ◽  
Olyesya Starodubova

Regulatory state agencies propose new solutions on regulating relationship in agriculture. Countries with developed agriculture have various national public institutions with a wide range of functions. They develop public policies, set standards, issue licenses and other permissions, do inspections, protect rights of agricultural products consumers, provide support to producers, and etc. Bodies regulating relationship in agriculture act in accordance with the general regulatory trends. Their activity is influenced by modernization and reformation processes, such as deregulation in various forms, transition from a command and control model of regulation to new models providing incentives for producers to voluntarily compliance, risk-based approach introduction, etc. Regulatory tools are often not effective enough for a number of reasons. This work consists of three parts, it evaluates the current state of agriculture in specific actual areas. The first section investigates general trends in the development of regulatory theory and practice. The second section deals with the problems of protecting farmers from unfair trade practices of suppliers and retail chains. The third section presents the results of the analysis of competing provisions on environmental protection and food safety. In conclusion, the authors give a system of new ways of regulation which can replace traditional ways of deterrence.


1982 ◽  
Vol 93 (1) ◽  
pp. 15-23 ◽  
Author(s):  
M Chalfie ◽  
J N Thomson

Tannic acid fixation reveals differences in the number of protofilaments between microtubules (MTs) in the nematode Caenorhabditis elegans. Most cells have MTs with 11 protofilaments but the six touch receptor neurons (the microtubule cells) have MTs with 15 protofilaments. No 13-protofilament (13-p) MT has been seen. The modified cilia of sensory neurons also possess unusual structures. The cilia contain nine outer doublets with A subfibers of 13 protofilaments and B subfibers of 11 protofilaments and a variable number of inner singlet MTs containing 11 protofilaments. The 15-p MTs but not the 11-p MTs are eliminated by colchicine-treatment or by mutation of the gene mec-7. Concomitantly, touch sensitivity is also lost. However, whereas colchicine treatment leads to the loss of all MTs from the microtubule cells, mutations in mec-7 result in the partial replacement of the 15-p MTs with 11-p MTs. Benzimidazoles (benomyl and nocodazole) have more general effects on C. elegans (slow growth, severe uncoordination, and loss of processes from the ventral cord) but do not affect the 15-p MTs. Benomyl will, however, disrupt the replacement 11-p MTs found in the microtubule cells of mec-7 mutants. The 11-p and 15-p MTs also respond differently to temperature and fixation conditions. It is likely that either type of MT will suffice for the proper outgrowth of the microtubule cell process, but only the 15-p MT can function in the specialized role of sensory transduction of the microtubule cells.


2019 ◽  
Vol 316 (2) ◽  
pp. H298-H310 ◽  
Author(s):  
Jin Zhang ◽  
Youhua Wang ◽  
Ling Chen ◽  
W. Gil Wier ◽  
Mordecai P. Blaustein

Plasma membrane Na+/Ca2+ exchanger-1 (NCX1) helps regulate the cytosolic Ca2+ concentration ([Ca2+]CYT) in arterial myocytes. NCX1 mediates both Ca2+ entry and exit and tends to promote net Ca2+ entry in partially constricted arteries. Mean blood pressure (telemetry) is elevated by ≈10 mmHg in transgenic (TG) mice that overexpress NCX1 specifically in smooth muscle. We tested the hypothesis that NCX1 overexpression mediates Ca2+ gain and elevated [Ca2+]CYT in exposed femoral arteries that also express the Ca2+ biosensor exogenous myosin light chain kinase. [Ca2+]CYT and the NCX1-dependent (SEA0400-sensitive) component, ≈15% of total basal constriction in controls, were increased in TG arteries, but constrictions to phenylephrine and ANG II were comparable in TG and control arteries. Normalized phenylephrine dose-response curves and constriction to 30 and 300 ng/kg iv ANG II were virtually identical in control and TG arteries. ANG II-evoked constrictions, superimposed on elevated basal tone, accounted for the larger blood pressure responses to ANG II in TG arteries. TG and control mouse arteries fit the same pCa-constriction relationship over a wide range of pCa (≈125–500 nM). Vasodilation to acetylcholine, normalized to passive diameter, was also comparable in TG and control arteries, implying normal endothelial function. TG artery Na+ nitroprusside (nitric oxide donor)-induced dilations were, however, shifted to lower Na+ nitroprusside concentrations, indicating that TG myocyte vasodilator mechanisms were augmented. Maximum arterial dilation was comparable in TG and control mice, although passive diameter was ≈6–7% smaller in TG mice. The changes in TG arteries were apparently largely functional rather than structural, despite the congenital hypertension. NEW & NOTEWORTHY Smooth muscle Na+/Ca2+ exchanger-1 transgene overexpression (TG mice) increases femoral artery basal cytosolic Ca2+ concentration ([Ca2+]CYT) and tone in vivo and raises blood pressure. Arterial constriction to phenylephrine and angiotensin II are normal but superimposed on the augmented basal [Ca2+]CYT and tone (constriction) in TG mouse arteries. Similar effects in resistance arteries would explain the elevated blood pressure. Acetylcholine-induced vasodilation is unimpaired, implying a normal endothelium, but TG arteries are hypersensitive to sodium nitroprusside.


2009 ◽  
Vol 23 (3) ◽  
pp. 104-112 ◽  
Author(s):  
Stefan Duschek ◽  
Heike Heiss ◽  
Boriana Buechner ◽  
Rainer Schandry

Recent studies have revealed evidence for increased pain sensitivity in individuals with chronically low blood pressure. The present trial explored whether pain sensitivity can be reduced by pharmacological elevation of blood pressure. Effects of the sympathomimetic midodrine on threshold and tolerance to heat pain were examined in 52 hypotensive persons (mean blood pressure 96/61 mmHg) based on a randomized, placebo-controlled, double-blind design. Heat stimuli were applied to the forearm via a contact thermode. Confounding of drug effects on pain perception with changes in skin temperature, temperature sensitivity, and mood were statistically controlled for. Compared to placebo, higher pain threshold and tolerance, increased blood pressure, as well as reduced heart rate were observed under the sympathomimetic condition. Increases in systolic blood pressure between points of measurement correlated positively with increases in pain threshold and tolerance, and decreases in heart rate were associated with increases in pain threshold. The findings underline the causal role of hypotension in the augmented pain sensitivity related to this condition. Pain reduction as a function of heart rate decrease suggests involvement of a baroreceptor-related mechanism in the pain attrition. The increased proneness of persons with chronic hypotension toward clinical pain is discussed.


Author(s):  
О. Кravchuk ◽  
V. Symonenkov ◽  
I. Symonenkova ◽  
O. Hryhorev

Today, more than forty countries of the world are engaged in the development of military-purpose robots. A number of unique mobile robots with a wide range of capabilities are already being used by combat and intelligence units of the Armed forces of the developed world countries to conduct battlefield intelligence and support tactical groups. At present, the issue of using the latest information technology in the field of military robotics is thoroughly investigated, and the creation of highly effective information management systems in the land-mobile robotic complexes has acquired a new phase associated with the use of distributed information and sensory systems and consists in the transition from application of separate sensors and devices to the construction of modular information subsystems, which provide the availability of various data sources and complex methods of information processing. The purpose of the article is to investigate the ways to increase the autonomy of the land-mobile robotic complexes using in a non-deterministic conditions of modern combat. Relevance of researches is connected with the necessity of creation of highly effective information and control systems in the perspective robotic means for the needs of Land Forces of Ukraine. The development of the Armed Forces of Ukraine management system based on the criteria adopted by the EU and NATO member states is one of the main directions of increasing the effectiveness of the use of forces (forces), which involves achieving the principles and standards necessary for Ukraine to become a member of the EU and NATO. The inherent features of achieving these criteria will be the transition to a reduction of tasks of the combined-arms units and the large-scale use of high-precision weapons and land remote-controlled robotic devices. According to the views of the leading specialists in the field of robotics, the automation of information subsystems and components of the land-mobile robotic complexes can increase safety, reliability, error-tolerance and the effectiveness of the use of robotic means by standardizing the necessary actions with minimal human intervention, that is, a significant increase in the autonomy of the land-mobile robotic complexes for the needs of Land Forces of Ukraine.


2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.


2020 ◽  
Author(s):  
Yong Zhang ◽  
Yang Tao ◽  
Yun Zhong ◽  
Jacqueline Thompson ◽  
Jamal Rahmani ◽  
...  

UNSTRUCTURED Lifestyle interventions have been recognised as a line treatment of non-communicable diseases. The aimed of this study was to evaluate a bespoke mHealth approach to delivers personalised feedback to improve blood pressure and weight for hypertensive patients in community settings. A total of 307 participants, 50 from each community, were expected to be in the intervention or control group. A professional health facilitator was assigned for each of the 6 communities. The primary outcomes of the study are the reduction in blood pressure and weight at baseline and post-intervention. Of 307 recruited,192 (62.5%) participants completed the study (intervention: 104 and control: 88). There was no difference in attrition rates between the two groups (33.5%vs41.9%, p=0.291). After 6-months of intensive feedback intervention through mHealth approach, patients had better blood pressure, weight, and BMI compared with control. People who were adherent to the intervention demonstrated a clinical benefit with regards to weight and blood pressure.


2021 ◽  
pp. 096100062110165
Author(s):  
Mohammadhiwa Abdekhoda ◽  
Fatemeh Ranjbaran ◽  
Asghar Sattari

This study was conducted with the aim of evaluating the role of information and information resources in the awareness, control, and prevention of COVID-19. This study was a descriptive-analytical survey in which 450 participants were selected for the study. The data collection instrument was a researcher-made questionnaire. Descriptive and inferential statistics were used to analyze the data through SPSS. The findings show that a wide range of mass media has become well known as information resources for COVID-19. Other findings indicate a significant statistical difference in the rate of using information resources during COVID-19 based on age and gender; however, this difference is not significant regarding the reliability of information resources with regard to age and gender. Health information has an undisputable role in the prevention and control of pandemic diseases such as COVID-19. Providing accurate, reliable, and evidence-based information in a timely manner for the use of resources and information channels related to COVID-19 can be a fast and low-cost strategic approach in confronting this disease.


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