scholarly journals HESC-derived sensory neurons reveal an unexpected role for PIEZO2 in nociceptor mechanotransduction

2019 ◽  
Author(s):  
Katrin Schrenk-Siemens ◽  
Jörg Pohle ◽  
Charlotte Rostock ◽  
Muad Abd El Hay ◽  
Ruby M. Lam ◽  
...  

AbstractSomatosensation, the detection and transduction of external and internal stimuli, has fascinated scientists for centuries. But still, some of the mechanisms how distinct stimuli are detected and transduced are not entirely understood. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification. Additionally, the accessibility to human pluripotent stem cells and the possibility to generate and study human sensory neurons has enriched the somatosensory research field.Based on our previous work, the generation of functional human mechanoreceptors, we describe here the generation of hESC-derived nociceptor-like cells. We show that by varying the differentiation strategy, we can produce different nociceptive subpopulations. One protocol in particular allowed the generation of a sensory neuron population, homogeneously expressing TRPV1, a prototypical marker for nociceptors. Accordingly, we find the cells to homogenously respond to capsaicin, to become sensitized upon inflammatory stimuli, and to respond to temperature stimulation.Surprisingly, all of the generated subtypes show mechano-nociceptive characteristics and, quite unexpectedly, loss of mechanotransduction in the absence of PIEZO2.

2019 ◽  
Vol 16 (2) ◽  
pp. 258-275 ◽  
Author(s):  
Navjeet Kaur

Background:A wide variety of biological activities are exhibited by N, O and S containing heterocycles and recently, many reports appeared for the synthesis of these heterocycles. The synthesis of heterocycles with the help of metal and non-metal catalyst has become a highly rewarding and important method in organic synthesis. This review article concentrated on the synthesis of S-heterocylces in the presence of metal and non-metal catalyst. The synthesis of five-membered S-heterocycles is described here.Objective:There is a need for the development of rapid, efficient and versatile strategy for the synthesis of heterocyclic rings. Metal, non-metal and organocatalysis involving methods have gained prominence because traditional conditions have disadvantages such as long reaction times, harsh conditions and limited substrate scope.Conclusion:The metal-, non-metal-, and organocatalyst assisted organic synthesis is a highly dynamic research field. For ßthe chemoselective and efficient synthesis of heterocyclic molecules, this protocol has emerged as a powerful route. Various methodologies in the past few years have been pointed out to pursue more sustainable, efficient and environmentally benign procedures and products. Among these processes, the development of new protocols (catalysis), which avoided the use of toxic reagents, are the focus of intense research.


2020 ◽  
Vol 47 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Garry D. Carnegie

ABSTRACT This response to the recent contribution by Matthews (2019) entitled “The Past, Present, and Future of Accounting History” specifically deals with the issues associated with concentrating on counting publication numbers in examining the state of a scholarly research field at the start of the 2020s. It outlines several pitfalls with the narrowly focused publications count analysis, in selected English language journals only, as provided by Matthews. The commentary is based on three key arguments: (1) accounting history research and publication is far more than a “numbers game”; (2) trends in the quality of the research undertaken and published are paramount; and (3) international publication and accumulated knowledge in accounting history are indeed more than a collection of English language publications. The author seeks to contribute to discussion and debate between accounting historians and other researchers for the benefit and development of the international accounting history community and global society.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masashi Nakatani ◽  
Yasuaki Kobayashi ◽  
Kota Ohno ◽  
Masaaki Uesaka ◽  
Sayako Mogami ◽  
...  

AbstractThe human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception.


Author(s):  
Xiaochen Zhang ◽  
Lanxin Hui ◽  
Linchao Wei ◽  
Fuchuan Song ◽  
Fei Hu

Electric power wheelchairs (EPWs) enhance the mobility capability of the elderly and the disabled, while the human-machine interaction (HMI) determines how well the human intention will be precisely delivered and how human-machine system cooperation will be efficiently conducted. A bibliometric quantitative analysis of 1154 publications related to this research field, published between 1998 and 2020, was conducted. We identified the development status, contributors, hot topics, and potential future research directions of this field. We believe that the combination of intelligence and humanization of an EPW HMI system based on human-machine collaboration is an emerging trend in EPW HMI methodology research. Particular attention should be paid to evaluating the applicability and benefits of the EPW HMI methodology for the users, as well as how much it contributes to society. This study offers researchers a comprehensive understanding of EPW HMI studies in the past 22 years and latest trends from the evolutionary footprints and forward-thinking insights regarding future research.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3192
Author(s):  
Nicolas Giacoletto ◽  
Frédéric Dumur

Over the past several decades, photopolymerization has become an active research field, and the ongoing efforts to develop new photoinitiating systems are supported by the different applications in which this polymerization technique is involved—including dentistry, 3D and 4D printing, adhesives, and laser writing. In the search for new structures, bis-chalcones that combine two chalcones’ moieties within a unique structure were determined as being promising photosensitizers to initiate both the free-radical polymerization of acrylates and the cationic polymerization of epoxides. In this review, an overview of the different bis-chalcones reported to date is provided. Parallel to the mechanistic investigations aiming at elucidating the polymerization mechanisms, bis-chalcones-based photoinitiating systems were used for different applications, which are detailed in this review.


2021 ◽  
Vol 1 (1) ◽  
pp. 4-24
Author(s):  
Jun Ochiai ◽  
Yutaka Niihara ◽  
Joan Oliva

Cell and gene therapies have been developing dramatically over the past decade. To face and adapt to the development of these new therapies, the Food and Drug Administration (FDA) wrote and updated new guidelines from 2016 and keep updating them. Mesenchymal stem cells (MSCs) are the most used cells for treatment, far ahead from the induced pluripotent stem cells (iPSCs), based on registered clinical trials at clinicaltrials.gov. They are widely used because of their differentiation capacity and their anti-inflammatory properties, but some controversies still require clear answers. Additional studies are needed to determine the dosage, the number, and the route of injections (location and transplantation method), and if allogenic MSCs are safe compared to autologous MSC injection, including their long-term effect. In this review, we summarize the research our company is conducting with the adipose stromal cells in engineering cell sheets and their potential application.


2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yong He ◽  
Hongfu Huang ◽  
Dong Li ◽  
Chunming Shi ◽  
Sarah J. Wu

We present a literature review on quality and operations management problems in food supply chains. In food industry, the quality of the food products declines over time and should be addressed in the supply chain operations management. Managing food supply chains with operations management methods not only generates economic benefit, but also contributes to environmental and social benefits. The literature on this topic has been burgeoning in the past few years. Since 2005, more than 100 articles have been published on this topic in major operations research and management science journals. In this literature review, we concentrate on the quantitative models in this research field and classify the related articles into four categories, that is, storage problems, distribution problems, marketing problems, and food traceability and safety problems. We hope that this review serves as a reference for interested researchers and a starting point for those who wish to explore it further.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shingo Ishihara ◽  
Alia M. Obeidat ◽  
David L. Wokosin ◽  
Dongjun Ren ◽  
Richard J. Miller ◽  
...  

Abstract Background C–C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model. Methods DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents. Results WT, but not Ccr2 null, mice displayed knee hyperalgesia 2–16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM. Conclusions The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1129
Author(s):  
Marvin Martens ◽  
Rob Stierum ◽  
Emma L. Schymanski ◽  
Chris T. Evelo ◽  
Reza Aalizadeh ◽  
...  

Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Christopher Richardson

PurposeWithin the expatriation subset of the wider IB literature, the focus of research has been on contemporary contextual factors. The purpose of this paper is to link the present to the past by investigating how the individual expatriate experience may be affected by a colonial legacy between host and home countries.Design/methodology/approachGiven the exploratory nature of this study, a qualitative interview-based approach eliciting thick, detailed descriptions of the practical experiences of seven Japanese expatriate managers working in Malaysia was adopted. These were supplemented by additional interviews with three host-country nationals who work alongside some of the expatriates. The data were analysed through a two-stage coding process.FindingsThe expatriate respondents were largely unanimous in their view that the colonial past between the two countries had no negative impact on their experiences in Malaysia, and the Malaysian interviewees corroborated this. On the contrary, the majority of the expatriates actually spoke positively about their experiences. This was especially true for expatriates in both the tourism and education/research field whose work was linked in some way to the period of Japanese occupation.Research limitations/implicationsThe small, single-context nature of the investigation limits generalisation. There are also many particularities in this study (the nature of Japanese-Malaysian postcolonial relations, cultural values of the Malaysians and Japanese, and so on) that are perhaps not easily relatable to other contexts. Having said this, qualitative research is not always geared towards generalisability but rather towards contextual intricacies and nuances.Originality/valueWhile most of the extant literature on expatriation has examined largely contemporary factors, this paper explores the impact of more historical events on the expatriate experience. Although such events may seem distant from an expatriate's current activities, this study suggests that in certain circumstances, they may have a lingering effect.


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