Ion channel regulation of gut immunity

Mounting evidence indicates that gastrointestinal (GI) homeostasis hinges on communications among many cellular networks including the intestinal epithelium, the immune system, and both intrinsic and extrinsic nerves innervating the gut. The GI tract, especially the colon, is the home base for gut microbiome which dynamically regulates immune function. The gut\u27s immune system also provides an effective defense against harmful pathogens entering the GI tract while maintaining immune homeostasis to avoid exaggerated immune reaction to innocuous food and commensal antigens which are important causes of inflammatory disorders such as coeliac disease and inflammatory bowel diseases (IBD). Various ion channels have been detected in multiple cell types throughout the GI tract. By regulating membrane properties and intracellular biochemical signaling, ion channels play a critical role in synchronized signaling among diverse cellular components in the gut that orchestrates the GI immune response. This work focuses on the role of ion channels in immune cells, non-immune resident cells, and neuroimmune interactions in the gut at the steady state and pathological conditions. Understanding the cellular and molecular basis of ion channel signaling in these immune-related pathways and initial testing of pharmacological intervention will facilitate the development of ion channel-based therapeutic approaches for the treatment of intestinal inflammation

Renewable energy and economic growth hypothesis: Evidence from N-11 countries

In the recent years, the trend of environmental sustainability is rapidly increasing by adopting renewable energy resources. However, the main concern is that whether renewable energy consumption contributes to economic growth. To investigate the issue, this study analyzes renewable energy led economic growth hypothesis in the Next-11 economies over the period 1990–2020. Also, this study aims to examine the influence of industry value added, gross national expenditure, and trade openness on economic growth of these economies. Along with the second-generation panel unit root test, this study employed the nonparametric panel data approach, i.e., quantile method of moments regression. The estimated results reveal the slopes coefficients are heterogeneous and cross-sectional dependency is present in the panel. The non-parametric approach reveals that validity of renewable energy led growth hypothesis. Also, the industry value added, gross national expenditure, and trade openness are found positively affecting economic growth of these economies. The panel causality test gives indication of the two way causal association between the variables. Based on the obtained results, policy implications are also provided for governors and researchers

How should we define a nociceptor in the gut-brain axis?

In the past few years, there has been extraordinary interest in how the gut communicates with the brain. This is because substantial and gathering data has emerged to suggest that sensory nerve pathways between the gut and brain may contribute much more widely in heath and disease, than was originally presumed. In the skin, the different types of sensory nerve endings have been thoroughly characterized, including the morphology of different nerve endings and the sensory modalities they encode. This knowledge is lacking for most types of visceral afferents, particularly spinal afferents that innervate abdominal organs, like the gut. In fact, only recently have the nerve endings of spinal afferents in any visceral organ been identified. What is clear is that spinal afferents play the major role in pain perception from the gut to the brain. Perhaps surprisingly, the majority of spinal afferent nerve endings in the gut express the ion channel TRPV1, which is often considered to be a marker of nociceptive neurons. And, a majority of gut-projecting spinal afferent neurons expressing TRPV1 are activated at low thresholds, in the normal physiological range, well below the normal threshold for detection of painful sensations. This introduces a major conundrum regarding visceral nociception. How should we define a nociceptor in the gut? We discuss the notion that nociception from the gut wall maybe a process encrypted into multiple different morphological types of spinal afferent nerve ending, rather than a single class of sensory ending, like free-endings, suggested to underlie nociception in skin

Modification of neurogenic colonic motor behaviours by chemogenetic ablation of calretinin neurons

How the enteric nervous system determines the pacing and propagation direction of neurogenic contractions along the colon remains largely unknown. We used a chemogenetic strategy to ablate enteric neurons expressing calretinin (CAL). Mice expressing human diphtheria toxin receptor (DTR) in CAL neurons were generated by crossin

MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel

Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-δ (PKCδ) signaling. Collectively, our data find a TRPV

Bloch surface plasmon enhanced blue emission from InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods

InGaN/GaN light-emitting diode structures with Al-coated GaN nanorods were fabricated by using soft ultraviolet nanoimprint lithography. The intensity of light emission was found to be greatly enhanced due to the strong near-fields confined at the interface of Al/GaN and extended to the multiple quantum wells (MQWs) active region. The dynamics of carrier recombination and plasmon-enhanced Raman scattering were also investigated, providing a progressive view on the effective energy transfer between MQWs and surface plasmons.This work was supported by Special Funds for Major State Basic Research Project (Nos. 2011CB301900 and 2012CB619304), the Hi-tech Research Project (No. 2014AA032605), National Nature Science Foundation of China (Nos. 11104130, 61274003, 60990311, 61176063, and 61422401), the Program for New Century Excellent Talents in University (No. NCET-11-0229), Nature Science Foundation of Jiangsu Province (Nos. BK2011556, BK2011010, BK2010385, BY2013077, and BE2011132), Funds of Key Laboratory (No. 9140C140102120C14), Scientific Innovation Research of College Graduate in Jiangsu Province (CXZZ12_0052), PAPD, the Fundamental Research Funds for the Central Universities, the Research Funds from NJUYangzhou Institute of Opto-electronics, and the Australian Research Council Discovery Early Career Researcher Award (DE130101700)

Kir6.1- and SUR2-dependent KATP over-activity disrupts intestinal motility in murine models of Cantu Syndrome

Cantύ Syndrome (CS), caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunit genes, is frequently accompanied by gastrointestinal (GI) dysmotility, and we describe one CS patient who required an implanted intestinal irrigation system for successful stooling. We used gene-modified mice to assess the underlying KATP channel subunits in gut smooth muscle, and to model the consequences of altered KATP channels in CS gut. We show that Kir6.1/SUR2 subunits underlie smooth muscle KATP channels throughout the small intestine and colon. Knock-in mice, carrying human KCNJ8 and ABCC9 CS mutations in the endogenous loci, exhibit reduced intrinsic contractility throughout the intestine, resulting in death when weaned onto solid food in the most severely affected animals. Death is avoided by weaning onto a liquid gel diet, implicating intestinal insufficiency and bowel impaction as the underlying cause, and GI transit is normalized by treatment with the KATP inhibitor glibenclamide. We thus define the molecular basis of intestinal KATP channel activity, the mechanism by which overactivity results in GI insufficiency, and a viable approach to therapy