GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord

The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also for coordinating downstream biochemical signaling pathways. At glutamatergic synapses in the adult CNS an overwhelming body of evidence indicates that the NMDA receptor (NMDAR) component of synaptic responses is dominated by NMDARs containing the GluN2A subunit, while NMDARs containing GluN2B, GluN2C, or GluN2D play minor roles in synaptic transmission. Here, we discovered NMDAR-mediated synaptic responses with characteristics not described elsewhere in the adult CNS. We found that GluN2A-containing receptors contribute little to synaptic NMDAR responses while GluN2B dominates at synapses of lamina I neurons in the adult spinal cord. In addition, we provide evidence for a GluN2D-mediated synaptic NMDAR component in adult lamina I neurons. Strikingly, the charge transfer mediated by GluN2D far exceeds that of GluN2A and is comparable to that of GluN2B. Lamina I forms a disti

The Prion Protein Ligand, Stress-Inducible Phosphoprotein 1, Regulates Amyloid-beta Oligomer Toxicity

In Alzheimer\u27s disease (AD), soluble amyloid-beta oligomers (A beta Os) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrPC). However, it is unknown whether other ligands of PrPC can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrPC in the vicinity of the A beta O binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in A beta O toxicity. We confirmed the specific binding of A beta Os and STI1 to the PrP and showed that STI1 efficiently inhibited A beta O binding to PrP in vitro (IC50 of similar to 70 nM) and also decreased A beta O binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented A beta O-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to A beta O-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both A beta O binding to PrPC and PrPC-dependent A beta O toxicity were inhibited by TPR2A, the PrPC-interacting domain of STI1. Additionally, PrPC-STI1 engagement activated alpha 7 nicotinic acetylcholine receptors, which participated in neuroprotection against A beta O-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrPC ligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset A beta O-induced toxicity

Spatio-temporal analysis of malaria incidence at the village level in a malaria-endemic area in Hainan, China

<p>Abstract</p> <p>Background</p> <p>Malaria incidence in China's Hainan province has dropped significantly, since Malaria Programme of China Global Fund Round 1 was launched. To lay a foundation for further studies to evaluate the efficacy of Malaria Programme and to help with public health planning and resource allocation in the future, the temporal and spatial variations of malaria epidemic are analysed and areas and seasons with a higher risk are identified at a fine geographic scale within a malaria endemic county in Hainan.</p> <p>Methods</p> <p>Malaria cases among the residents in each of 37 villages within hyper-endemic areas of Wanning county in southeast Hainan from 2005 to 2009 were geo-coded at village level based on residence once the patients were diagnosed. Based on data so obtained, purely temporal, purely spatial and space-time scan statistics and geographic information systems (GIS) were employed to identify clusters of time, space and space-time with elevated proportions of malaria cases.</p> <p>Results</p> <p>Purely temporal scan statistics suggested clusters in 2005,2006 and 2007 and no cluster in 2008 and 2009. Purely spatial clustering analyses pinpointed the most likely cluster as including three villages in 2005 and 2006 respectively, sixteen villages in 2007, nine villages in 2008, and five villages in 2009, and the south area of Nanqiao town as the most likely to have a significantly high occurrence of malaria. The space-time clustering analysis found the most likely cluster as including three villages in the south of Nanqiao town with a time frame from January 2005 to May 2007.</p> <p>Conclusions</p> <p>Even in a small traditional malaria endemic area, malaria incidence has a significant spatial and temporal heterogeneity on the finer spatial and temporal scales. The scan statistics enable the description of this spatiotemporal heterogeneity, helping with clarifying the epidemiology of malaria and prioritizing the resource assignment and investigation of malaria on a finer geographical scale in endemic areas.</p

Using Visual Cues to Enhance Haptic Feedback for Palpation on Virtual Model of Soft Tissue

This paper explores methods that make use of visual cues aimed at generating actual haptic sensation to the user, namely pseudo-haptics. We propose a new pseudo-haptic feedback based method capable of conveying 3D haptic information and combining visual haptics with force feedback to enhance the user’s haptic experience. We focused on an application related to tumor identification during palpation and evaluated the proposed method in an experimental study where users interacted with a haptic device and graphical interface while exploring a virtual model of soft tissue, which represented stiffness distribution of a silicone phantom tissue with embedded hard inclusions. The performance of hard inclusion detection using force feedback only, pseudo-haptic feedback only, and the combination of the two feedbacks were compared with the direct hand touch. The combination method and direct hand touch had no significant difference in the detection results. Compared with the force feedback alone, our method increased the sensitivity by 5%, the positive predictive value by 4%, and decreased detection time by 48.7%. The proposed methodology has great potential for robot-assisted minimally invasive surgery and in all applications where remote haptic feedback is needed

Novel hybrid adaptive controller for manipulation in complex perturbation environments

© 2015 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In this paper we present a hybrid control scheme, combining the advantages of task-space and joint-space control. The controller is based on a human-like adaptive design, which minimises both control effort and tracking error. Our novel hybrid adaptive controller has been tested in extensive simulations, in a scenario where a Baxter robot manipulator is affected by external disturbances in the form of interaction with the environment and tool-like end-effector perturbations. The results demonstrated improved performance in the hybrid controller over both of its component parts. In addition, we introduce a novel method for online adaptation of learning parameters, using the fuzzy control formalism to utilise expert knowledge from the experimenter. This mechanism of meta-learning induces further improvement in performance and avoids the need for tuning through trial testing

Ciliary parathyroid hormone signaling activates transforming growth factor-β to maintain intervertebral disc homeostasis during aging

© 2018 The Author(s). Degenerative disc disease (DDD) is associated with intervertebral disc degeneration of spinal instability. Here, we report that the cilia of nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in the discs. We found that mechanical stress promotes transport of parathyroid hormone 1 receptor (PTH1R) to the cilia and enhances parathyroid hormone (PTH) signaling in NP cells. PTH induces transcription of integrin αvβ6 to activate the transforming growth factor (TGF)-β-connective tissue growth factor (CCN2)-matrix proteins signaling cascade. Intermittent injection of PTH (iPTH) effectively attenuates disc degeneration of aged mice by direct signaling through NP cells, specifically improving intervertebral disc height and volume by increasing levels of TGF-β activity, CCN2, and aggrecan. PTH1R is expressed in both mouse and human NP cells. Importantly, knockout PTH1R or cilia in the NP cells results in significant disc degeneration and blunts the effect of PTH on attenuation of aged discs. Thus, mechanical stress-induced transport of PTH1R to the cilia enhances PTH signaling, which helps maintain intervertebral disc homeostasis, particularly during aging, indicating therapeutic potential of iPTH for DDD

What Does Nature Tell Us About Anthropogenic Aerosol Indirect Effects?

No abstract availabl

Applications of 2D-layered palladium diselenide and its van der Waals heterostructures in electronics and optoelectronics

The rapid development of two-dimensional (2D) transition-metal dichalcogenides has been possible owing to their special structures and remarkable properties. In particular, palladium diselenide (PdSe2) with a novel pentagonal structure and unique physical characteristics have recently attracted extensive research interest. Consequently, tremendous research progress has been achieved regarding the physics, chemistry, and electronics of PdSe2. Accordingly, in this review, we recapitulate and summarize the most recent research on PdSe2, including its structure, properties, synthesis, and applications. First, a mechanical exfoliation method to obtain PdSe2 nanosheets is introduced, and large-area synthesis strategies are explained with respect to chemical vapor deposition and metal selenization. Next, the electronic and optoelectronic properties of PdSe2 and related heterostructures, such as field-effect transistors, photodetectors, sensors, and thermoelectric devices, are discussed. Subsequently, the integration of systems into infrared image sensors on the basis of PdSe2 van der Waals heterostructures is explored. Finally, future opportunities are highlighted to serve as a general guide for physicists, chemists, materials scientists, and engineers. Therefore, this comprehensive review may shed light on the research conducted by the 2D material community.Web of Science131art. no. 14

Histological and transcriptome-wide level characteristics of fetal myofiber hyperplasia during the second half of gestation in Texel and Ujumqin sheep

<p>Abstract</p> <p>Background</p> <p>Whether myofibers increase with a pulsed-wave mode at particular developmental stages or whether they augment evenly across developmental stages in large mammals is unclear. Additionally, the molecular mechanisms of myostatin in myofiber hyperplasia at the fetal stage in sheep remain unknown. Using the first specialized transcriptome-wide sheep oligo DNA microarray and histological methods, we investigated the gene expression profile and histological characteristics of developing fetal ovine longissimus muscle in Texel sheep (high muscle and low fat), as a myostatin model of natural mutation, and Ujumqin sheep (low muscle and high fat). Fetal skeletal muscles were sampled at 70, 85, 100, 120, and 135 d of gestation.</p> <p>Results</p> <p>Myofiber number increased sharply with a pulsed-wave mode at certain developmental stages but was not augmented evenly across developmental stages in fetal sheep. The surges in myofiber hyperplasia occurred at 85 and 120 d in Texel sheep, whereas a unique proliferative surge appeared at 100 d in Ujumqin sheep. Analysis of the microarray demonstrated that immune and hematological systems' development and function, lipid metabolism, and cell communication were the biological functions that were most differentially expressed between Texel and Ujumqin sheep during muscle development. Pathways associated with myogenesis and the proliferation of myoblasts, such as calcium signaling, chemokine (C-X-C motif) receptor 4 signaling, and vascular endothelial growth factor signaling, were affected significantly at specific fetal stages, which underpinned fetal myofiber hyperplasia and postnatal muscle hypertrophy. Moreover, we identified some differentially expressed genes between the two breeds that could be potential myostatin targets for further investigation.</p> <p>Conclusions</p> <p>Proliferation of myofibers proceeded in a pulsed-wave mode at particular fetal stages in the sheep. The myostatin mutation changed the gene expression pattern in skeletal muscle at a transcriptome-wide level, resulting in variation in myofiber phenotype between Texel and Ujumqin sheep during the second half of gestation. Our findings provide a novel and dynamic description of the effect of myostatin on skeletal muscle development, which contributes to understanding the biology of muscle development in large mammals.</p