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https://www.readbyqxmd.com/read/29786422/mechanisms-regulating-the-association-of-protein-phosphatase-1-with-spinophilin-and-neurabin
#1
Michael C Edler, Asma B Salek, Darryl S Watkins, Harjot Kaur, Cameron W Morris, Bryan K Yamamoto, Anthony J Baucum
Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homolog neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins...
May 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29785027/targeting-g-quadruplex-dna-as-cognitive-function-therapy-for-atr-x-syndrome
#2
Norifumi Shioda, Yasushi Yabuki, Kouya Yamaguchi, Misaki Onozato, Yue Li, Kenji Kurosawa, Hideyuki Tanabe, Nobuhiko Okamoto, Takumi Era, Hiroshi Sugiyama, Takahito Wada, Kohji Fukunaga
Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#3
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784760/formation-of-the-intrathymic-dendritic-cell-pool-requires-ccl21-mediated-recruitment-of-ccr7-progenitors-to-the-thymus
#4
Emilie J Cosway, Izumi Ohigashi, Karin Schauble, Sonia M Parnell, William E Jenkinson, Sanjiv Luther, Yousuke Takahama, Graham Anderson
During αβ T cell development in the thymus, migration of newly selected CD4+ and CD8+ thymocytes into medullary areas enables tolerance mechanisms to purge the newly selected αβ TCR repertoire of autoreactive specificities. Thymic dendritic cells (DC) play key roles in this process and consist of three distinct subsets that differ in their developmental origins. Thus, plasmacytoid DC and Sirpα+ conventional DC type 2 are extrathymically derived and enter into the thymus via their respective expression of the chemokine receptors CCR9 and CCR2...
May 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29784759/of-what-use-is-connectomics-a-personal-perspective-on-the-drosophila-connectome
#5
REVIEW
Ian A Meinertzhagen
The brain is a network of neurons and its biological output is behaviour. This is an exciting age, with a growing acknowledgement that the comprehensive compilation of synaptic circuits densely reconstructed in the brains of model species is now both technologically feasible and a scientifically enabling possibility in neurobiology, much as 30 years ago genomics was in molecular biology and genetics. Implemented by huge advances in electron microscope technology, especially focused ion beam-scanning electron microscope (FIB-SEM) milling (see Glossary), image capture and alignment, and computer-aided reconstruction of neuron morphologies, enormous progress has been made in the last decade in the detailed knowledge of the actual synaptic circuits formed by real neurons, in various brain regions of the fly Drosophila It is useful to distinguish synaptic pathways that are major, with 100 or more presynaptic contacts, from those that are minor, with fewer than about 10; most neurites are both presynaptic and postsynaptic, and all synaptic sites have multiple postsynaptic dendrites...
May 20, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#6
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29784128/immunosurveillance-of-cancer-and-the-heat-shock-protein-cd91-pathway
#7
Robert J Binder
The intracellular functions of heat shock proteins (HSPs) as chaperones of macromolecules are well known. Current observations point to a role of these chaperones in initiating and modulating immune responses to tumors via receptor(s) on dendritic cells. In this article we provide an insight into, and a basis for, the importance of these HSP-mediated immune responses in rejecting nascent and emerging tumors.
May 16, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29783988/tolerogenic-bone-marrow-derived-dendritic-cells-induce-neuroprotective-regulatory-t-cells-in-a-model-of-parkinson-s-disease
#8
Charles R Schutt, Howard E Gendelman, R Lee Mosley
BACKGROUND: Administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases regulatory T cell (Treg) number and function with control of neuroinflammation and neuronal protection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Recently, we demonstrated in an early phase 1 clinical trial that GM-CSF also improves motor skills in PD patients. However, the mechanisms of Treg induction and its effects on neuroprotective responses remain unknown...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782948/dendritic-peg-outer-shells-enhance-serum-stability-of-polymeric-micelles
#9
Hao-Jui Hsu, Yanxiao Han, Michael Cheong, Petr Král, Seungpyo Hong
A higher surface density of poly(ethylene glycol) (PEG) on polymeric micelles enhances their stability in serum, leading to improved plasma circulation. To obtain fundamental, mechanistic understanding of the PEG effect associated with polymeric architecture/configuration, we have synthesized PEGylated dendron-based copolymers (PDCs) and linear block copolymers (LBCs) with similar molecular weights. These copolymers formed dendron (hyperbranched) and linear micelles, respectively, which were compared in terms of their stabilities in serum, micelle-serum protein interactions, and in vivo biodistributions...
May 18, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29782803/amphiphilic-hybrid-dendritic-linear-molecules-as-nanocarriers-for-shape-dependent-antitumor-drug-delivery
#10
Yifei Guo, Ting Wang, Shuang Zhao, Meihua Han, Zhengqi Dong, Xiangtao Wang, Yanhong Wang
Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs. G2-C18 not only affected the drug-loading content of nanoparticles, but also influenced the morphology of HCPT nanoparticles, the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio...
May 21, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29782700/nonionic-dendritic-and-carbohydrate-based-amphiphiles-self-assembly-and-transport-behavior
#11
Suchita Prasad, Katharina Achazi, Boris Schade, Rainer Haag, Sunil K Sharma
Herein, a new series of non-ionic dendritic and carbohydrate based amphiphiles is synthesized employing biocompatible starting materials and studied for supramolecular aggregate formation in aqueous solution. The dendritic amphiphiles 12 and 13 possessing poly(glycerol) [G2.0] as hydrophilic unit and C-10 and C-18 hydrophobic alkyl chains, respectively, exhibit low critical aggregation concentration (CAC) in the order of 10-5 m and hydrodynamic diameters in the 8-10 nm range and supplemented by cryogenic transmission electron microscopy...
May 21, 2018: Macromolecular Bioscience
https://www.readbyqxmd.com/read/29782659/self-suspended-nanomesh-scaffold-for-ultrafast-flexible-photodetectors-based-on-organic-semiconducting-crystals
#12
Lei Zhang, Nadiia Pasthukova, Yifan Yao, Xiaolan Zhong, Egon Pavlica, Gvido Bratina, Emanuele Orgiu, Paolo Samorì
Self-standing nanostructures are of fundamental interest in materials science and nanoscience and are widely used in (opto-)electronic and photonic devices as well as in micro-electromechanical systems. To date, large-area and self-standing nanoelectrode arrays assembled on flexible substrates have not been reported. Here the fabrication of a hollow nanomesh scaffold on glass and plastic substrates with a large surface area over 1 mm2 and ultralow leakage current density (≈1-10 pA mm-2 @ 2 V) across the empty scaffold is demonstrated...
May 21, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29782555/langerin-dcs-regulate-innate-il-17-production-in-the-oral-mucosa-during-candida-albicans-mediated-infection
#13
Florian Sparber, Tamas Dolowschiak, Sarah Mertens, Laura Lauener, Björn E Clausen, Nicole Joller, Patrizia Stoitzner, Roxane Tussiwand, Salomé LeibundGut-Landmann
The opportunistic fungal pathogen Candida albicans frequently causes diseases such as oropharyngeal candidiasis (OPC) in immunocompromised individuals. Although it is well appreciated that the cytokine IL-17 is crucial for protective immunity against OPC, the cellular source and the regulation of this cytokine during infection are still a matter of debate. Here, we directly visualized IL-17 production in the infected tongue of experimentally infected mice, thereby demonstrating that this key cytokine is expressed by three complementary subsets of CD90+ leukocytes: RAG-dependent αβ and γδ T cells, as well as RAG-independent ILCs...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782541/an-unappreciated-role-for-neutrophil-dc-hybrids-in-immunity-to-invasive-fungal-infections
#14
J Scott Fites, Michael Gui, John F Kernien, Paige Negoro, Zeina Dagher, David B Sykes, Jeniel E Nett, Michael K Mansour, Bruce S Klein
Neutrophils are classically defined as terminally differentiated, short-lived cells; however, neutrophils can be long-lived with phenotypic plasticity. During inflammation, a subset of neutrophils transdifferentiate into a population called neutrophil-DC hybrids (PMN-DCs) having properties of both neutrophils and dendritic cells. While these cells ubiquitously appear during inflammation, the role of PMN-DCs in disease remains poorly understood. We observed the differentiation of PMN-DCs in pre-clinical murine models of fungal infection: blastomycosis, aspergillosis and candidiasis...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29781994/a-drosophila-in-vivo-injury-model-for-studying-neuroregeneration-in-the-peripheral-and-central-nervous-system
#15
Dan Li, Feng Li, Pavithran Guttipatti, Yuanquan Song
The regrowth capacity of damaged neurons governs neuroregeneration and functional recovery after nervous system trauma. Over the past few decades, various intrinsic and extrinsic inhibitory factors involved in the restriction of axon regeneration have been identified. However, simply removing these inhibitory cues is insufficient for successful regeneration, indicating the existence of additional regulatory machinery. Drosophila melanogaster, the fruit fly, shares evolutionarily conserved genes and signaling pathways with vertebrates, including humans...
May 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29781786/sitagliptin-rescues-memory-deficits-in-parkinsonian-rats-via-upregulating-bdnf-to-prevent-neuron-and-dendritic-spine-loss
#16
Jing Li, Shuhu Zhang, Chenye Li, Mei Li, Lan Ma
OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative disease with high morbidity among adults worldwide that causes tremendous trouble to people's lives. The purpose of this study was to investigate the impact of sitagliptin on PD and its potential mechanism. METHODS: First, the memory of rats in each group was evaluated with the Morris water maze (MWM) test and the passive avoidance test. Then, both brain-derived neurotrophic factor (BDNF) protein and mRNA levels were detected by ELISA and qPCR assays, respectively...
May 21, 2018: Neurological Research
https://www.readbyqxmd.com/read/29780980/charge-and-hydration-structure-of-dendritic-polyelectrolytes-molecular-simulations-of-polyglycerol-sulphate
#17
Rohit Nikam, Xiao Xu, Matthias Ballauff, Matej Kanduč, Joachim Dzubiella
Macromolecules based on dendritic or hyperbranched polyelectrolytes have been emerging as high potential candidates for biomedical applications. Here we study the charge and solvation structure of dendritic polyglycerol sulphate (dPGS) of generations 0 to 3 in aqueous sodium chloride solution by explicit-solvent molecular dynamics computer simulations. We characterize dPGS by calculating several important properties such as relevant dPGS radii, molecular distributions, the solvent accessible surface area, and the partial molecular volume...
May 21, 2018: Soft Matter
https://www.readbyqxmd.com/read/29780470/stable-2d-anti-ferromagnetically-coupled-fluorenyl-radical-dendrons
#18
Jian Wang, Gakhyun Kim, María Eugenia Sandoval-Salinas, Hoa Phan, Tullimilli Y Gopalakrishna, Xuefeng Lu, David Casanova, Dongho Kim, Jishan Wu
We report the first class of stable, two-dimensional (2D) anti-ferromagnetically coupled dendritic polyradicaloids. A kinetically blocked fluorenyl radical was used to build up the first and second generation dendrons FR-G1 and FR-G2 containing three and seven fluorenyl units, respectively. The neighboring fluorenyl radicals in FR-G1 and FR-G2 show moderate anti-ferromagnetic exchange interaction, resulting in a doublet and quartet ground state, respectively, with a small doublet-quartet energy gap. From FR-G1 to FR-G2 , the energy gap decreased and the two-photon absorption was enhanced owing to more extended 2D π-conjugation...
April 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29780316/resonance-analysis-as-a-tool-for-characterizing-functional-division-of-layer-5-pyramidal-neurons
#19
Melvin A Felton, Alfred B Yu, David L Boothe, Kelvin S Oie, Piotr J Franaszczuk
Evidence suggests that layer 5 pyramidal neurons can be divided into functional zones with unique afferent connectivity and membrane characteristics that allow for post-synaptic integration of feedforward and feedback inputs. To assess the existence of these zones and their interaction, we characterized the resonance properties of a biophysically-realistic compartmental model of a neocortical layer 5 pyramidal neuron. Consistent with recently published theoretical and empirical findings, our model was configured to have a "hot zone" in distal apical dendrite and apical tuft where both high- and low-threshold Ca2+ ionic conductances had densities 1-2 orders of magnitude higher than anywhere else in the apical dendrite...
2018: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/29779874/a-gabaergic-feedback-shapes-dopaminergic-input-on-the-drosophila-mushroom-body-to-promote-appetitive-long-term-memory
#20
Alice Pavlowsky, Johann Schor, Pierre-Yves Plaçais, Thomas Preat
Memory consolidation is a crucial step for long-term memory (LTM) storage. However, we still lack a clear picture of how memory consolidation is regulated at the neuronal circuit level. Here, we took advantage of the well-described anatomy of the Drosophila olfactory memory center, the mushroom body (MB), to address this question in the context of appetitive LTM. The MB lobes, which are made by the fascicled axons of the MB intrinsic neurons, are organized into discrete anatomical modules, each covered by the terminals of a defined type of dopaminergic neuron (DAN) and the dendrites of a corresponding type of MB output neuron (MBON)...
May 9, 2018: Current Biology: CB
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