Meteorite Like Nano and Pico Space Devices and Robots and the Polar Region of Mars

第3回極域科学シンポジウム/第35回南極隕石シンポジウム 11月29日（木）、30日（金） 国立国語研究所 2階講

Effects of articaine on [3H]noradrenaline release from cortical and spinal cord slices prepared from normal and streptozotocin-induced diabetic rats and compared to lidocaine.

Since a significant proportion of diabetic patients have clinical or subclinical neuropathy, there may be concerns about the use of local anaesthetics. The present study was designed to determine and compare the effects of articaine, a widely used anaesthetic in dental practice, and lidocaine on the resting and axonal stimulation-evoked release of [3H]noradrenaline ([3H]NA) in prefrontal cortex slices and the release of [3H]NA in spinal cord slices prepared from non-diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03+/-2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment. Articaine and lidocaine inhibited the stimulation-evoked release in a concentration-dependent manner and increased the resting release by two to six times. These effects indicate an inhibitory action of these anaesthetics on Na+- and K+-channels. There was no difference in clinically important nerve conduction between non-diabetic and diabetic rats, as measured by the release of transmitter in response to axonal stimulation. The uptake and resting release of NA was significantly higher in the brain slices prepared from diabetic rats, but there were no differences in the spinal cord. For the adverse effects, the effects of articaine on K+ channels (resting release) are more pronounced compared to lidocaine. In this respect, articaine has a thiophene ring with high lipid solubility, which may present potential risks for some patients

Conduit integrity is compromised during acute lymph node expansion

Lymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis

The International Surface Pressure Databank version 2

The International Surface Pressure Databank (ISPD) is the world's largest collection of global surface and sea-level pressure observations. It was developed by extracting observations from established international archives, through international cooperation with data recovery facilitated by the Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative, and directly by contributing universities, organizations, and countries. The dataset period is currently 1768–2012 and consists of three data components: observations from land stations, marine observing systems, and tropical cyclone best track pressure reports. Version 2 of the ISPD (ISPDv2) was created to be observational input for the Twentieth Century Reanalysis Project (20CR) and contains the quality control and assimilation feedback metadata from the 20CR. Since then, it has been used for various general climate and weather studies, and an updated version 3 (ISPDv3) has been used in the ERA-20C reanalysis in connection with the European Reanalysis of Global Climate Observations project (ERA-CLIM). The focus of this paper is on the ISPDv2 and the inclusion of the 20CR feedback metadata. The Research Data Archive at the National Center for Atmospheric Research provides data collection and access for the ISPDv2, and will provide access to future versions

Neurochemical Changes in the Mouse Hippocampus Underlying the Antidepressant Effect of Genetic Deletion of P2X7 Receptors.

Recent investigations have revealed that the genetic deletion of P2X7 receptors (P2rx7) results in an antidepressant phenotype in mice. However, the link between the deficiency of P2rx7 and changes in behavior has not yet been explored. In the present study, we studied the effect of genetic deletion of P2rx7 on neurochemical changes in the hippocampus that might underlie the antidepressant phenotype. P2X7 receptor deficient mice (P2rx7-/-) displayed decreased immobility in the tail suspension test (TST) and an attenuated anhedonia response in the sucrose preference test (SPT) following bacterial endotoxin (LPS) challenge. The attenuated anhedonia was reproduced through systemic treatments with P2rx7 antagonists. The activation of P2rx7 resulted in the concentration-dependent release of [3H]glutamate in P2rx7+/+ but not P2rx7-/- mice, and the NR2B subunit mRNA and protein was upregulated in the hippocampus of P2rx7-/- mice. The brain-derived neurotrophic factor (BDNF) expression was higher in saline but not LPS-treated P2rx7-/- mice; the P2rx7 antagonist Brilliant blue G elevated and the P2rx7 agonist benzoylbenzoyl ATP (BzATP) reduced BDNF level. This effect was dependent on the activation of NMDA and non-NMDA receptors but not on Group I metabotropic glutamate receptors (mGluR1,5). An increased 5-bromo-2-deoxyuridine (BrdU) incorporation was also observed in the dentate gyrus derived from P2rx7-/- mice. Basal level of 5-HT was increased, whereas the 5HIAA/5-HT ratio was lower in the hippocampus of P2rx7-/- mice, which accompanied the increased uptake of [3H]5-HT and an elevated number of [3H]citalopram binding sites. The LPS-induced elevation of 5-HT level was absent in P2rx7-/- mice. In conclusion there are several potential mechanisms for the antidepressant phenotype of P2rx7-/- mice, such as the absence of P2rx7-mediated glutamate release, elevated basal BDNF production, enhanced neurogenesis and increased 5-HT bioavailability in the hippocampus

Gebiss: an ImageJ plugin for the specification of ground truth and the performance evaluation of 3D segmentation algorithms.

Background: Image segmentation is a crucial step in quantitative microscopy that helps to define regions of tissues, cells or subcellular compartments. Depending on the degree of user interactions, segmentation methods can be divided into manual, automated or semi-automated approaches. 3D image stacks usually require automated methods due to their large number of optical sections. However, certain applications benefit from manual or semi-automated approaches. Scenarios include the quantification of 3D images with poor signal-to-noise ratios or the generation of so-called ground truth segmentations that are used to evaluate the accuracy of automated segmentation methods. Results: We have developed Gebiss; an ImageJ plugin for the interactive segmentation, visualisation and quantification of 3D microscopic image stacks. We integrated a variety of existing plugins for threshold-based segmentation and volume visualisation. Conclusions: We demonstrate the application of Gebiss to the segmentation of nuclei in live Drosophila embryos and the quantification of neurodegeneration in Drosophila larval brains. Gebiss was developed as a cross-platform ImageJ plugin and is freely available on the web at http://imaging.bii.a-star.edu.sg/projects/gebiss

Pivotal Role of the α2A-Adrenoceptor in Producing Inflammation and Organ Injury in a Rat Model of Sepsis

Background: Norepinephrine (NE) modulates the responsiveness of macrophages to proinflammatory stimuli through the activation of adrenergic receptors (ARs). Being part of the stress response, early increases of NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source of NE release in the early stage of cecal ligation and puncture (CLP)-induced sepsis in rats, which then stimulates TNF-a production in Kupffer cells (KCs) through the activation of the a2-AR. It is important to know which of the three a2-AR subtypes (i.e., a2A, a2B or a2C) is responsible for the upregulation of TNF-a production. The aim of this study was to determine the contribution of a2A-AR in this process. Methodology/Principal Findings: Adult male rats underwent CLP and KCs were isolated 2 h later. Gene expression of a2A-AR was determined. In additional experiments, cultured KCs were incubated with NE with or without BRL-44408 maleate, a specific a2A-AR antagonist, and intraportal infusion of NE for 2 h with or without BRL-44408 maleate was carried out in normal animals. Finally, the impact of a2A-AR activation by NE was investigated under inflammatory conditions (i.e., endotoxemia and CLP). Gene expression of the a2A-AR subtype was significantly upregulated after CLP. NE increased the release of TNF-a in cultured KCs, which was specifically inhibited by the a2A-AR antagonist BRL-44408. Equally, intraportal NE infusion increased TNF-a gene expression in KCs and plasma TNF-a which was also abrogated by co-administration of BRL-44408. NE also potentiated LPS-induced TNF-a release via the a2A-AR in vitro and in vivo. This potentiation of TNF-a release by NE was mediated through the a2A-AR coupled Gai protein and the activation of the p38 MAP kinase. Treatment of septic animals with BRL-44408 suppressed TNF-a, prevented multiple organ injury and significantly improved survival from 45% to 75%. Conclusions/Significance: Our novel finding is that hyperresponsiveness to a2-AR stimulation observed in sepsis is primarily due to an increase in a2A-AR expression in KCs. This appears to be in part responsible for the increased proinflammatory response and ensuing organ injury in sepsis. These findings provide important feasibility information for further developing the a2A-AR antagonist as a new therapy for sepsis

Expression of mutant exon 1 huntingtin fragments in human neural stem cells and neurons causes inclusion formation and mitochondrial dysfunction.

Robust cellular models are key in determining pathological mechanisms that lead to neurotoxicity in Huntington's disease (HD) and for high throughput pre‐clinical screening of potential therapeutic compounds. Such models exist but mostly comprise non‐human or non‐neuronal cells that may not recapitulate the correct biochemical milieu involved in pathology. We have developed a new human neuronal cell model of HD, using neural stem cells (ReNcell VM NSCs) stably transduced to express exon 1 huntingtin (HTT) fragments with variable length polyglutamine (polyQ) tracts. Using a system with matched expression levels of exon 1 HTT fragments, we investigated the effect of increasing polyQ repeat length on HTT inclusion formation, location, neuronal survival, and mitochondrial function with a view to creating an in vitro screening platform for therapeutic screening. We found that expression of exon 1 HTT fragments with longer polyQ tracts led to the formation of intra‐nuclear inclusions in a polyQ length‐dependent manner during neurogenesis. There was no overt effect on neuronal viability, but defects of mitochondrial function were found in the pathogenic lines. Thus, we have a human neuronal cell model of HD that may recapitulate some of the earliest stages of HD pathogenesis, namely inclusion formation and mitochondrial dysfunction

A single cell high content assay detects mitochondrial dysfunction in iPSC-derived neurons with mutations in SNCA

Mitochondrial dysfunction is implicated in many neurodegenerative diseases including Parkinson's disease (PD). Induced pluripotent stem cells (iPSCs) provide a unique cell model for studying neurological diseases. We have established a high-content assay that can simultaneously measure mitochondrial function, morphology and cell viability in iPSC-derived dopaminergic neurons. iPSCs from PD patients with mutations in SNCA and unaffected controls were differentiated into dopaminergic neurons, seeded in 384-well plates and stained with the mitochondrial membrane potential dependent dye TMRM, alongside Hoechst-33342 and Calcein-AM. Images were acquired using an automated confocal screening microscope and single cells were analysed using automated image analysis software. PD neurons displayed reduced mitochondrial membrane potential and altered mitochondrial morphology compared to control neurons. This assay demonstrates that high content screening techniques can be applied to the analysis of mitochondria in iPSC-derived neurons. This technique could form part of a drug discovery platform to test potential new therapeutics for PD and other neurodegenerative diseases