Jiangnicholson0102

Human leukocyte antigen (HLA) class I and II are known to have association with severe cutaneous adverse reactions (SCARs) when exposing to certain drug treatment. Due to genetic differences at population level, drug hypersensitivity reactions are varied, and thus common pharmacogenetics markers for one country might be different from another country, for instance, HLA-A*3101 is associated with carbamazepine (CBZ)-induced SCARs in European and Japanese while HLA-B*1502 is associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) among Taiwanese and Southeast Asian. Such differences pose a major challenge to prevent drug hypersensitivity when pharmacogenetics cannot be ubiquitously and efficiently translated into clinic. Therefore, a population-wide study of the distribution of HLA-pharmacogenetics markers is needed. This work presents a study of Thai HLA alleles on both HLA class I and II genes from 470 unrelated Thai individuals by means of polymerase chain reaction sequence-sker distribution in Thailand that could be used as a reference for other Southeast Asian countries to validate the feasibility of their future pharmacogenetics deployment. Copyright © 2020 Satapornpong, Jinda, Jantararoungtong, Koomdee, Chaichan, Pratoomwun, Na Nakorn, Aekplakorn, Wilantho, Ngamphiw, Tongsima and Sukasem.High-throughput liquid chromatography-mass spectrometry (LC-MS)-based metabolomics can provide the holistic analysis of the low molecular weight endogenous metabolites in cells and reflect the changes of cellular regulation and metabolic pathways. Our study designed to reveal the potentially pharmacological effects of dioscin on SW480 rectal cancer cells using nontargeted metabolomics method to probe into small molecular metabolites and pathway changes. After the cell assay of proliferation, apoptosis, migration, and invasion, the dioscin-treated cell samples were prepared for nontargeted metabolomics analysis based on LC-MS tool to describe the metabolic profiles. Dioscin has prevented cell proliferation and accelerated cell apoptosis, and it also inhibited the SW480 rectal cancer cells' migration and invasion. A total of 22 metabolites were selected as promising biomarkers of pharmacological reaction of dioscin to rectal cancer, and eight highly correlated pathways including D-glutamine and D-glutamate metabolism, pyruvate metabolism, arachidonic acid metabolism, phenylalanine metabolism, tryptophan metabolism, glycolysis or gluconeogenesis, citrate cycle (TCA cycle), and butanoate metabolism were identified. It showed that strategies based on cell metabolomics are helpful tools to discover the small molecular metabolites to elucidate the action mechanism of drug. Copyright © 2020 Wang, Yu and Li.Automatic alignment of brain anatomy in a standard space is a key step when processing magnetic resonance imaging for group analyses. Such brain registration is prone to failure, and the results are therefore typically reviewed visually to ensure quality. There is however no standard, validated protocol available to perform this visual quality control (QC). We propose here a standardized QC protocol for brain registration, with minimal training overhead and no required knowledge of brain anatomy. We validated the reliability of three-level QC ratings (OK, Maybe, Fail) across different raters. Nine experts each rated N = 100 validation images, and reached moderate to good agreement (kappa from 0.4 to 0.68, average of 0.54 ± 0.08), with the highest agreement for "Fail" images (Dice from 0.67 to 0.93, average of 0.8 ± 0.06). We then recruited volunteers through the Zooniverse crowdsourcing platform, and extracted a consensus panel rating for both the Zooniverse raters (N = 41) and the expert raters. The agreement between expert and Zooniverse panels was high (kappa = 0.76). Overall, our protocol achieved a good reliability when performing a two level assessment (Fail vs. OK/Maybe) by an individual rater, or aggregating multiple three-level ratings (OK, Maybe, Fail) from a panel of experts (3 minimum) or non-experts (15 minimum). Our brain registration QC protocol will help standardize QC practices across laboratories, improve the consistency of reporting of QC in publications, and will open the way for QC assessment of large datasets which could be used to train automated QC systems. Copyright © 2020 Benhajali, Badhwar, Spiers, Urchs, Armoza, Ong, Pérusse and Bellec.Social interactions are a crucial part of human life. Understanding the neural underpinnings of social interactions is a challenging task that the hyperscanning method has been trying to tackle over the last two decades. Here, we review the existing literature and evaluate the current state of the hyperscanning method. We review the type of methods (fMRI, M/EEG, and fNIRS) that are used to measure brain activity from more than one participant simultaneously and weigh their pros and cons for hyperscanning. Further, we discuss different types of analyses that are used to estimate brain networks and synchronization. Lastly, we present results of hyperscanning studies in the context of different cognitive functions and their relations to social interactions. All in all, we aim to comprehensively present methods, analyses, and results from the last 20 years of hyperscanning research. Copyright © 2020 Czeszumski, Eustergerling, Lang, Menrath, Gerstenberger, Schuberth, Schreiber, Rendon and König.Objective To investigate the projections the cerebrospinal fluid-contacting (CSF-contacting) nucleus receives from the diencephalon and to speculate on the functional significance of these connections. Methods The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in SD rats according to the experimental formula of the stereotaxic coordinates. Animals were perfused 7-10 days after the injection, and the diencephalon was sliced at 40 μm with a freezing microtome. CB-immunofluorescence was performed on all diencephalic sections. The features of CB-positive neuron distribution in the diencephalon were observed with a fluorescence microscope. Results The retrograde labeled CB-positive neurons were found in the epithalamus, subthalamus, and hypothalamus. Three functional diencephalic areas including 43 sub-regions revealed projections to the CSF-contacting nucleus. The CB-positive neurons were distributed in different density ranges sparse, moderate, and dense. Conclusion Based on the connectivity patterns of the CSF-contacting nucleus that receives anatomical inputs from the diencephalon, we preliminarily assume that the CSF-contacting nucleus participates in homeostasis regulation, visceral activity, stress, emotion, pain and addiction, and sleeping and arousal. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the diencephalon, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulations. Copyright © 2020 Song, Li, Zhai, Li, Bao, Shan, Hong, Cao and Zhang.The plasticity of the central nervous system (CNS) in response to neuronal activity has been suggested as early as 1894 by Cajal (1894). CNS plasticity has first been studied with a focus on neuronal structures. However, in the last decade, myelin plasticity has been unraveled as an adaptive mechanism of importance, in addition to the previously described processes of myelin repair. Indeed, it is now clear that myelin remodeling occurs along with life and adapts to the activity of neuronal networks. Until now, it has been considered as a two-part dialog between the neuron and the oligodendroglial lineage. However, other glial cell types might be at play in myelin plasticity. In the present review, we first summarize the key structural parameters for myelination, we then describe how neuronal activity modulates myelination and finally discuss how other glial cells could participate in myelinic adaptivity. Copyright © 2020 Ronzano, Thetiot, Lubetzki and Desmazieres.Acid-sensing ion channels (ASICs) are H+-activated neuronal Na+ channels. They are involved in fear behavior, learning, neurodegeneration after ischemic stroke and in pain sensation. ASIC activation has so far been studied only with fast pH changes, although the pH changes associated with many roles of ASICs are slow. It is currently not known whether slow pH changes can open ASICs at all. Here, we investigated to which extent slow pH changes can activate ASIC1a channels and induce action potential signaling. To this end, ASIC1a current amplitudes and charge transport in transfected Chinese hamster ovary cells, and ASIC-mediated action potential signaling in cultured cortical neurons were measured in response to defined pH ramps of 1-40 s duration from pH 7.4 to pH 6.6 or 6.0. A kinetic model of the ASIC1a current was developed and integrated into the Hodgkin-Huxley action potential model. Interestingly, whereas the ASIC1a current amplitude decreased with slower pH ramps, action potential firing was higher upon intermediate than fast acidification in cortical neurons. Indeed, fast pH changes (10 s to complete, ASIC1a activation is inefficient. Therefore, it is likely that currently unknown modulatory mechanisms allow ASIC activity in situations such as ischemia and inflammation. Copyright © 2020 Alijevic, Bignucolo, Hichri, Peng, Kucera and Kellenberger.Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca2+ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement. Copyright © 2020 Broadhead and Miles.The cortex is crucial for many behaviors, ranging from sensory-based behaviors to working memory and social behaviors. To gain an in-depth understanding of the contribution to these behaviors, cellular and sub-cellular recordings from both individual and populations of cortical neurons are vital. However, techniques allowing such recordings, such as two-photon imaging and whole-cell electrophysiology, require absolute stability of the head, a requirement not often fulfilled in freely moving animals. Here, we review and compare behavioral paradigms that have been developed and adapted for the head-fixed preparation, which together offer the needed stability for live recordings of neural activity in behaving animals. We also review how the head-fixed preparation has been used to explore the function of primary sensory cortices, posterior parietal cortex (PPC) and anterior lateral motor (ALM) cortex in sensory-based behavioral tasks, while also discussing the considerations of performing such recordings. Overall, this review highlights the head-fixed preparation as allowing in-depth investigation into the neural activity underlying behaviors by providing highly controllable settings for precise stimuli presentation which can be combined with behavioral paradigms ranging from simple sensory detection tasks to complex, cross-modal, memory-guided decision-making tasks.