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https://www.readbyqxmd.com/read/29134656/long-term-dynamic-synaptic-reorganization-after-gabaergic-precursor-cell-transplantation-into-adult-mouse-spinal-cord
#1
Ida J Llewellyn-Smith, Allan I Basbaum, João M Bráz
Transplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE-derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP-expressing MGE-derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short- (5-6 weeks) or long-term (4-6 months) transplants...
November 13, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/29134249/early-siv-and-hiv-infection-promotes-the-lilrb2-mhc-i-inhibitory-axis-in-cdcs
#2
Lamine Alaoui, Gustavo Palomino, Sandy Zurawski, Gerard Zurawski, Sixtine Coindre, Nathalie Dereuddre-Bosquet, Camille Lecuroux, Cecile Goujard, Bruno Vaslin, Christine Bourgeois, Pierre Roques, Roger Le Grand, Olivier Lambotte, Benoit Favier
Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29128831/dynamic-morphogenesis-of-dendritic-structures-formation-in-hen-egg-white-lysozyme-fibrils-doped-with-magnetic-nanoparticles
#3
Natália Tomašovičová, Po-Sheng Hu, Cyun-Lun Zeng, Mária Huráková, Kornel Csach, Jozefína Majorošová, Martina Kubovčíková, Peter Kopčanský
In this research, the dynamic process of aggregation that forms microflower morphology in solution of lysozyme amyloid fibrils doped with spherical or spindle-like magnetic nanoparticles during the process of drying as well as their final microstructures were investigated. The prepared lysozyme amyloid fibrils as well as their mixtures with in-lab synthesized magnetic particles, which were prepared by adding the nanoparticles to the fibrils solution after the process of fibrillation was done, were characterized using brightfield trans-illumination-mode optical microscope, atomic force microscopy (AFM) and scanning electron microscope (SEM)...
November 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29123470/regulation-of-ampa-receptor-trafficking-by-protein-ubiquitination
#4
REVIEW
Jocelyn Widagdo, Sumasri Guntupalli, Se E Jang, Victor Anggono
The molecular mechanisms underlying plastic changes in the strength and connectivity of excitatory synapses have been studied extensively for the past few decades and remain the most attractive cellular models of learning and memory. One of the major mechanisms that regulate synaptic plasticity is the dynamic adjustment of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor content on the neuronal plasma membrane. The expression of surface AMPA receptors (AMPARs) is controlled by the delicate balance between the biosynthesis, dendritic transport, exocytosis, endocytosis, recycling and degradation of the receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29122984/effects-of-mutating-%C3%AE-tubulin-lysine-40-on-sensory-dendrite-development
#5
Brian V Jenkins, Harriet A J Saunders, Helena L Record, Dena M Johnson-Schlitz, Jill Wildonger
Microtubules are essential to neuronal structure and function. Axonal and dendritic microtubules are enriched in post-translational modifications that impact microtubule dynamics, transport, and microtubule-associated proteins. Acetylation of α-tubulin lysine 40 (K40) is a prominent, conserved modification of neuronal microtubules. However, the cellular role of microtubule acetylation remains controversial. To resolve how microtubule acetylation might affect neuronal morphogenesis we mutated endogenous α-tubulin in vivo using a new fly strain that facilitates the rapid knock-in of designer α-tubulin alleles...
November 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29118918/image-guided-dendritic-cell-based-vaccine-immunotherapy-in-murine-carcinoma-models
#6
REVIEW
Bin Wang, Chong Sun, Sijia Wang, Na Shang, Matteo Figini, Quanhong Ma, Shanzhi Gu, Daniele Procissi, Vahid Yaghmai, Guoxin Li, Andrew Larson, Zhuoli Zhang
In recent decades, immunotherapy has undergone extensive developments for oncologic therapy applications. Dendritic cells (DCs) plays a fundamental role in cell-based vaccination immunotherapy against various types of cancer. It involves stimulating innate and adaptive immunity, in particular cytotoxic T-cell mediated antitumor effects, against targeted tumors and has been studied in both preclinical and clinical settings. Nevertheless, clinical outcomes have been unsatisfying. The antitumor response requires sufficient migration of viable DCs from primary administration site to targeted tumors through related lymphatics...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29117560/timed-synaptic-inhibition-shapes-nmda-spikes-influencing-local-dendritic-processing-and-global-i-o-properties-of-cortical-neurons
#7
Michael Doron, Giuseppe Chindemi, Eilif Muller, Henry Markram, Idan Segev
The NMDA spike is a long-lasting nonlinear phenomenon initiated locally in the dendritic branches of a variety of cortical neurons. It plays a key role in synaptic plasticity and in single-neuron computations. Combining dynamic system theory and computational approaches, we now explore how the timing of synaptic inhibition affects the NMDA spike and its associated membrane current. When impinging on its early phase, individual inhibitory synapses strongly, but transiently, dampen the NMDA spike; later inhibition prematurely terminates it...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29114037/reducing-eif4e-eif4g-interactions-restores-the-balance-between-protein-synthesis-and-actin-dynamics-in-fragile-x-syndrome-model-mice
#8
Emanuela Santini, Thu N Huynh, Francesco Longo, So Yeon Koo, Edward Mojica, Laura D'Andrea, Claudia Bagni, Eric Klann
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism spectrum disorder. FXS is caused by silencing of the FMR1 gene, which encodes fragile X mental retardation protein (FMRP), an mRNA-binding protein that represses the translation of its target mRNAs. One mechanism by which FMRP represses translation is through its association with cytoplasmic FMRP-interacting protein 1 (CYFIP1), which subsequently sequesters and inhibits eukaryotic initiation factor 4E (eIF4E). CYFIP1 shuttles between the FMRP-eIF4E complex and the Rac1-Wave regulatory complex, thereby connecting translational regulation to actin dynamics and dendritic spine morphology, which are dysregulated in FXS model mice that lack FMRP...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29112734/memantine-prevents-acute-radiation-induced-toxicities-at-hippocampal-excitatory-synapses
#9
Joseph G Duman, Jeffrey Dinh, Wei Zhou, Henry Cham, Vasilis C Mavratsas, Matea Paveškovic, Shalaka Mulherkar, Susan L McGovern, Kimberley F Tolias, David R Grosshans
Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing eGFP were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy...
November 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29112124/gene-regulatory-network-rewiring-in-the-immune-cells-associated-with-cancer
#10
Pengyong Han, Chandrasekhar Gopalakrishnan, Haiquan Yu, Edwin Wang
The gene regulatory networks (GRNs) of immune cells not only indicate cell identity but also reveal the dynamic changes of immune cells when comparing their GRNs. Cancer immunotherapy has advanced in the past few years. Immune-checkpoint blockades (i.e., blocking PD-1, PD-L1, or CTLA-4) have shown durable clinical effects on some patients with various advanced cancers. However, major gaps in our knowledge of immunotherapy have been recognized. To fill these gaps, we conducted a systematic analysis of the GRNs of key immune cell subsets (i...
November 7, 2017: Genes
https://www.readbyqxmd.com/read/29111749/unravelling-the-formation-mechanism-of-dendritic-fibrous-nanosilica
#11
Ayan Maity, Avik Das, Debasis Sen, Subhasish Mazumder, Vivek Polshettiwar
We studied the formation mechanism of dendritic fibrous nanosilica (DFNS) that involves several intriguing dynamical steps. Through electron microscopy and real-time small-angle X-ray scattering studies, it has been demonstrated that the structural evolu-tion of bi-continuous microemulsion droplets (BMDs) and their subsequent coalescence, yielding nano-reactor template, is responsible for to the formation of complex DFNS morphology. The role of co-surfactant has been found to be quite crucial, which allowed the understanding of this intricate mechanism involving the complex interplay of self-assembly, dynamics of BMDs formation and coa-lescence...
November 7, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29106931/interplay-between-keratinocytes-and-myeloid-cells-drives-dengue-virus-spread-in-human-skin
#12
Parichat Duangkhae, Geza Erdos, Kate D Ryman, Simon C Watkins, Louis D Falo, Ernesto T A Marques, Simon M Barratt-Boyes
The skin is the site of dengue virus (DENV) transmission following the bite of an infected mosquito, but the contribution of individual cell types within skin to infection is unknown. We studied the dynamics of DENV infection in human skin explants using quantitative in situ imaging. DENV replicated primarily in the epidermis and induced a transient interferon-α response. DENV infected a wide range of cells, including Langerhans cells, macrophages, dermal dendritic cells (DC), mast cells, fibroblasts and lymphatic endothelium, but keratinocytes were the earliest targets of infection and made up 60% of infected cells over time...
October 26, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29097544/er-mitochondria-tethering-by-pdzd8-regulates-ca-2-dynamics-in-mammalian-neurons
#13
Yusuke Hirabayashi, Seok-Kyu Kwon, Hunki Paek, Wolfgang M Pernice, Maëla A Paul, Jinoh Lee, Parsa Erfani, Ashleigh Raczkowski, Donald S Petrey, Liza A Pon, Franck Polleux
Interfaces between organelles are emerging as critical platforms for many biological responses in eukaryotic cells. In yeast, the ERMES complex is an endoplasmic reticulum (ER)-mitochondria tether composed of four proteins, three of which contain a SMP (synaptotagmin-like mitochondrial-lipid binding protein) domain. No functional ortholog for any ERMES protein has been identified in metazoans. Here, we identified PDZD8 as an ER protein present at ER-mitochondria contacts. The SMP domain of PDZD8 is functionally orthologous to the SMP domain found in yeast Mmm1...
November 3, 2017: Science
https://www.readbyqxmd.com/read/29097502/inhibitor-of-serine-peptidase-2-enhances-leishmania-major-survival-in-the-skin-through-control-of-monocytes-and-monocyte-derived-cells
#14
Amy Goundry, Audrey Romano, Ana Paula C A Lima, Jeremy C Mottram, Elmarie Myburgh
Leishmania major is the causative agent of the neglected tropical disease, cutaneous leishmaniasis. In the mouse, protective immunity to Leishmania is associated with inflammatory responses. Here, we assess the dynamics of the inflammatory responses at the lesion site during experimental long-term, low-dose intradermal infection of the ear, employing noninvasive imaging and genetically modified L. major Significant infiltrates of neutrophils and monocytes occurred at 1-4 d and 2-4 wk, whereas dermal macrophage and dendritic cell (DC) numbers were only slightly elevated in the first days...
November 2, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29097383/mind-the-sr-gap-roles-of-slit-robo-gaps-in-neurons-brains-and-beyond
#15
REVIEW
Bethany Lucas, Jeff Hardin
The Slit-Robo GTPase-activating proteins (srGAPs) were first identified as potential Slit-Robo effectors that influence growth cone guidance. Given their N-terminal F-BAR, central GAP and C-terminal SH3 domains, srGAPs have the potential to affect membrane dynamics, Rho family GTPase activity and other binding partners. Recent research has clarified how srGAP family members act in distinct ways at the cell membrane, and has expanded our understanding of the roles of srGAPs in neuronal and non-neuronal cells...
November 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29091766/cns-neurons-deposit-laminin-%C3%AE-5-to-stabilize-synapses
#16
Mitchell H Omar, Meghan Kerrisk Campbell, Xiao Xiao, Qiaonan Zhong, William J Brunken, Jeffrey H Miner, Charles A Greer, Anthony J Koleske
Synapses in the developing brain are structurally dynamic but become stable by early adulthood. We demonstrate here that an α5-subunit-containing laminin stabilizes synapses during this developmental transition. Hippocampal neurons deposit laminin α5 at synapses during adolescence as connections stabilize. Disruption of laminin α5 in neurons causes dramatic fluctuations in dendritic spine head size that can be rescued by exogenous α5-containing laminin. Conditional deletion of laminin α5 in vivo increases dendritic spine size and leads to an age-dependent loss of synapses accompanied by behavioral defects...
October 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/29089443/detailed-dendritic-excitatory-inhibitory-balance-through-heterosynaptic-spike-timing-dependent-plasticity
#17
Naoki Hiratani, Tomoki Fukai
The balance between excitatory and inhibitory inputs is a key feature of cortical dynamics. Such a balance is arguably preserved in dendritic branches, yet its underlying mechanism and functional roles remain unknown. In this study, we developed computational models of heterosynaptic spike-timing-dependent plasticity (STDP) to show that the excitatory/inhibitory balance in dendritic branches is robustly achieved through heterosynaptic interactions between excitatory and inhibitory synapses. The model reproduces key features of experimental heterosynaptic STDP well, and provides analytical insights...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29089437/transient-hypoxemia-chronically-disrupts-maturation-of-preterm-fetal-ovine-subplate-neuron-arborization-and-activity
#18
Evelyn McClendon, Daniel C Shaver, Kiera Degener-O'Brien, Xi Gong, Thuan Nguyen, Anna Hoerder-Suabedissen, Zoltán Molnár, Claudia Mohr, Ben D Richardson, David J Rossi, Stephen A Back
Preterm infants are at risk for a broad spectrum of neurobehavioral disabilities associated with diffuse disturbances in cortical growth and development. During brain development, subplate neurons (SPNs) are a largely transient population that serves a critical role to establish functional cortical circuits. By dynamically integrating into developing cortical circuits they assist in consolidation of intra and extracortical circuits. Although SPNs reside in close proximity to cerebral white matter, which is particularly vulnerable to oxidative stress, the susceptibility of SPNs remains controversial...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29078331/lack-of-bace1-s-palmitoylation-reduces-amyloid-burden-and-mitigates-memory-deficits-in-transgenic-mouse-models-of-alzheimer-s-disease
#19
Robert J Andrew, Celia G Fernandez, Molly Stanley, Hong Jiang, Phuong Nguyen, Richard C Rice, Virginie Buggia-Prévot, Pierre De Rossi, Kulandaivelu S Vetrivel, Raza Lamb, Arnau Argemi, Emilie S Allaert, Elle M Rathbun, Sofia V Krause, Steven L Wagner, Angèle T Parent, David M Holtzman, Gopal Thinakaran
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, is axonally transported in neurons and accumulates in dystrophic neurites near cerebral amyloid deposits in AD. BACE1 is modified by S-palmitoylation at four juxtamembrane cysteine residues...
October 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29078305/%C3%AE-iii-spectrin-spinocerebellar-ataxia-type-5-mutation-reveals-a-dominant-cytoskeletal-mechanism-that-underlies-dendritic-arborization
#20
Adam W Avery, David D Thomas, Thomas S Hays
A spinocerebellar ataxia type 5 (SCA5) L253P mutation in the actin-binding domain (ABD) of β-III-spectrin causes high-affinity actin binding and decreased thermal stability in vitro. Here we show in mammalian cells, at physiological temperature, that the mutant ABD retains high-affinity actin binding. Significantly, we provide evidence that the mutation alters the mobility and recruitment of β-III-spectrin in mammalian cells, pointing to a potential disease mechanism. To explore this mechanism, we developed a Drosophila SCA5 model in which an equivalent mutant Drosophila β-spectrin is expressed in neurons that extend complex dendritic arbors, such as Purkinje cells, targeted in SCA5 pathogenesis...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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