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https://www.readbyqxmd.com/read/28218920/a-non-volatile-organic-electrochemical-device-as-a-low-voltage-artificial-synapse-for-neuromorphic-computing
#1
Yoeri van de Burgt, Ewout Lubberman, Elliot J Fuller, Scott T Keene, Grégorio C Faria, Sapan Agarwal, Matthew J Marinella, A Alec Talin, Alberto Salleo
The brain is capable of massively parallel information processing while consuming only ∼1-100 fJ per synaptic event. Inspired by the efficiency of the brain, CMOS-based neural architectures and memristors are being developed for pattern recognition and machine learning. However, the volatility, design complexity and high supply voltages for CMOS architectures, and the stochastic and energy-costly switching of memristors complicate the path to achieve the interconnectivity, information density, and energy efficiency of the brain using either approach...
February 20, 2017: Nature Materials
https://www.readbyqxmd.com/read/28207953/sgs1-a-neomorphic-nac52-allele-impairing-ptgs-through-sgs3-down-regulation
#2
Nicolas Butel, Ivan Le Masson, Nathalie Bouteiller, Hervé Vaucheret, Taline Elmayan
Post-transcriptional gene silencing (PTGS) is a defense mechanism that targets invading nucleic acids from endogenous (transposons) or exogenous (pathogens, transgenes) origins. Genetic screens based on the reactivation of silenced transgenes have long been used to identify cellular PTGS components and regulators. Here we show that the first isolated PTGS-deficient mutant, sgs1, is impaired in the transcription factor NAC52. This mutant exhibits striking similarities with a mutant impaired in the H3K4me3 demethylase JMJ14 isolated from the same genetic screen...
February 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28183734/skap2-is-required-for-%C3%AE-2-integrin-mediated-neutrophil-recruitment-and-functions
#3
Mark Boras, Stephanie Volmering, Arne Bokemeyer, Jan Rossaint, Helena Block, Bernadette Bardel, Veerle Van Marck, Barbara Heitplatz, Stefanie Kliche, Annegret Reinhold, Clifford Lowell, Alexander Zarbock
Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in β2 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin cytoplasmic domain, thereby being indispensable for β2 integrin activation and neutrophil recruitment...
February 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28157452/activated-%C3%AE-2-integrins-restrict-neutrophil-recruitment-during-murine-acute-pseudomonal-pneumonia
#4
Zachary S Wilson, Lawrence B Ahn, William S Serratelli, Matthew D Belley, Joanne Lomas-Neira, Mehmet Sen, Craig T Lefort
Rapid neutrophil recruitment is critical for the efficient clearance of bacterial pathogens from the lungs. While β2 integrins and their activation are required for neutrophil recruitment from postcapillary venules of the systemic circulation into inflamed tissues, the involvement of integrins in neutrophil recruitment in response to respiratory infection varies between bacterial pathogens. For stimuli eliciting β2 integrin-dependent neutrophil influx, including Pseudomonas aeruginosa, it remains unclear whether the activation of β2 integrins is an essential step in this process...
February 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28155884/the-molecular-basis-of-talin2-s-high-affinity-toward-%C3%AE-1-integrin
#5
Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P Hytönen, Chang-Guo Zhan, Cai Huang
Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β-integrin tails...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135265/%C3%AE-integrin-de-phosphorylation-by-the-density-enhanced-phosphatase-dep-1-attenuates-egfr-signaling-in-c-elegans
#6
Michael Walser, Christoph Alois Umbricht, Erika Fröhli, Paolo Nanni, Alex Hajnal
Density-Enhanced Phosphatase-1 (DEP-1) de-phosphorylates various growth factor receptors and adhesion proteins to regulate cell proliferation, adhesion and migration. Moreover, dep-1/scc1 mutations have been detected in various types of human cancers, indicating a broad tumor suppressor activity. During C. elegans development, DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling. Using a substrate-trapping DEP-1 mutant in a proteomics approach, we have identified the C. elegans β-integrin subunit PAT-3 as a specific DEP-1 substrate...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28131835/nano-mechanical-characterization-of-tension-sensitive-helix-bundles-in-talin-rod
#7
Koichiro Maki, Nobuhiko Nakao, Taiji Adachi
Tension-induced exposure of a cryptic signaling binding site is one of the most fundamental mechanisms in molecular mechanotransduction. Helix bundles in rod domains of talin, a tension-sensing protein at focal adhesions, unfurl under tension to expose cryptic vinculin binding sites. Although the difference in their mechanical stabilities would determine which helix bundle is tension-sensitive, their respective mechanical behaviors under tension have not been characterized. In this study, we evaluated the mechanical behaviors of residues 486-654 and 754-889 of talin, which form helix bundles with low and high tension-sensitivity, by employing AFM nano-tensile testing...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28117756/talin-modulation-by-a-synthetic-n-acylurea-derivative-reduces-angiogenesis-in-human-endothelial-cells
#8
I-Rang Lim, Hyung Joon Joo, Minseon Jeong, Jong-Ho Kim, Seung-Cheol Choi, Chungho Kim, Jong-Wha Jung, Soon Jun Hong
Talin is a focal adhesion protein that activates integrins and recruits other focal adhesion proteins. Talin regulates the interactions between integrins and the extracellular matrix, which are critical for endothelial cells during angiogenesis. In this study, we successfully synthesized a novel talin modulator, N-((2-(1H-indol-3-yl)ethyl)carbamoyl)-2-(benzo[d][1,3]dioxol-5-yloxy)acetamide, referred to as KCH-1521. KCH-1521 was determined to bind talin and modulate downstream signaling molecules of talin. After 24 h of treatment, KCH-1521 changed the cell morphology of human umbilical vein endothelial cells (HUVECs) and reduced focal adhesion protein expression including vinculin and paxillin...
January 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28101696/role-of-the-helix-in-talin-f3-domain-f3-helix-in-talin-mediated-integrin-activation
#9
Ang Li, Qiang Guo, Ailin Wei, Yaliang Zhou, Weiming Hu
Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin's capacity to activate integrin has never been explored before...
January 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28099903/talin-1-interaction-network-promotes-hepatocellular-carcinoma-progression
#10
Peng Chen, Xiaohu Zheng, Yonggang Zhou, Yechuan Xu, Lixin Zhu, Yeben Qian
Talin-1 is a known oncogene-associated protein. In this study, we set out to determine its role and mechanisms in hepatocellular carcinoma (HCC) progression. We found Talin-1 to be highly expressed in HCC cells relative to non-cancer liver epithelial cells and to promote tumor growth and metastasis. We used Whole Human Genome Oligo Microarray analysis with HCC cells and HCC cells in which Talin-1 was knocked down using shRNA to identify transcripts regulated by Talin-1. Of the 40,000 tested genes, 3099 were differentially expressed after Talin-1 knockdown; expression of 1924 genes was increased, while expression of 2175 was decreased...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096216/basal-filopodia-and-vascular-mechanical-stress-organize-fibronectin-into-pillars-bridging-the-mesoderm-endoderm-gap
#11
Yuki Sato, Kei Nagatoshi, Ayumi Hamano, Yuko Imamura, David Huss, Seiichi Uchida, Rusty Lansford
Cells may exchange information with other cells and tissues by exerting forces on the extracellular matrix (ECM). Fibronectin (FN) is an important ECM component that forms fibrils through cell contacts and creates directionally biased geometry. Here, we demonstrate that FN is deposited as pillars between widely separated germ layers, namely the somitic mesoderm and the endoderm, in quail embryos. Alongside the FN pillars, long filopodia protrude from the basal surfaces of somite epithelial cells. Loss-of-function of Ena/VASP, α5β1-integrins or talin in the somitic cells abolished the FN pillars, indicating that FN pillar formation is dependent on the basal filopodia through these molecules...
January 15, 2017: Development
https://www.readbyqxmd.com/read/28069919/calpain-mediated-proteolysis-of-talin-and-fak-regulates-adhesion-dynamics-necessary-for-axon-guidance
#12
Patrick C Kerstein, Kevin M Patel, Timothy M Gomez
Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca(2+)) is an essential signal for axon guidance that mediates opposing effects on growth cone motility. The diverse effects of Ca(2+) arise from the precise localization of Ca(2+) signals into microdomains containing specific Ca(2+) effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca(2+) signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28063985/revealing-the-three-dimensional-architecture-of-focal-adhesion-components-to-explain-ca-2-mediated-turnover-of-focal-adhesions
#13
Shu-Jing Chang, Ying-Chi Chen, Chi-Hsun Yang, Soon-Cen Huang, Ho-Kai Huang, Chun-Chun Li, Hans I-Chen Harn, Wen-Tai Chiu
BACKGROUND: Focal adhesions (FAs) are large, dynamic protein complexes located close to the plasma membrane, which serve as the mechanical linkages and a biochemical signaling hub of cells. The coordinated and dynamic regulation of focal adhesion is required for cell migration. Degradation, or turnover, of FAs is a major event at the trailing edge of a migratory cell, and is mediated by Ca(2+)/calpain-dependent proteolysis and disassembly. Here, we investigated how Ca(2+) influx induces cascades of FA turnover in living cells...
March 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28052935/d120-and-k152-within-the-ph-domain-of-t-cell-adapter-skap55-regulate-plasma-membrane-targeting-of-skap55-and-lfa-1-affinity-modulation-in-human-t-lymphocytes
#14
Amelie Witte, Bernhard Meineke, Jana Sticht, Lars Philipsen, Benno Kuropka, Andreas J Müller, Christian Freund, Burkhart Schraven, Stefanie Kliche
The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) is needed for T cell receptor (TCR) induced activation of LFA-1 to promote T cell adhesion and interaction with antigen presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src Kinase-Associated Phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its Pleckstrin Homology (PH) domain...
January 4, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27997081/uterine-focal-adhesion-dynamics-during-pregnancy-in-a-marsupial-sminthopsis-crassicaudata-dasyuridae
#15
Melanie K Laird, Michaela Turancova, Bronwyn M McAllan, Christopher R Murphy, Michael B Thompson
Alterations to the basal attachment points between the epithelium of the uterus and the underlying tissue in early pregnancy affect how easily the epithelium can be invaded by the implanting embryo. Attachment points- focal adhesions- disassemble to facilitate highly invasive implantation in rats, but species with less invasive implantation, including marsupials, may require different basal alterations for successful pregnancy. Here we used immunofluorescence microscopy and Western blotting to conduct the first study of basal plasma membrane dynamics in the uterus during marsupial pregnancy...
December 20, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
https://www.readbyqxmd.com/read/27974389/structure-and-lipid-binding-properties-of-the-kindlin-3-pleckstrin-homology-domain
#16
Tao Ni, Antreas C Kalli, Fiona B Naughton, Luke A Yates, Omar Naneh, Mirijam Kozorog, Gregor Anderluh, Mark S P Sansom, Robert J C Gilbert
Kindlins co-activate integrins alongside talin. They possess, like talin, a FERM domain (4.1-erythrin-radixin-moiesin domain) comprising F0-F3 subdomains, but with a pleckstrin homology (PH) domain inserted in the F2 subdomain that enables membrane association. We present the crystal structure of murine kindlin-3 PH domain determined at a resolution of 2.23 Å and characterise its lipid binding using biophysical and computational approaches. Molecular dynamics simulations suggest flexibility in the PH domain loops connecting β-strands forming the putative phosphatidylinositol phosphate (PtdInsP)-binding site...
February 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/27933836/fabrication-testing-and-simulation-of-all-solid-state-three-dimensional-li-ion-batteries
#17
A Alec Talin, Dmitry Ruzmetov, Andrei Kolmakov, Kim McKelvey, Nicholas Ware, Farid El Gabaly, Bruce Dunn, Henry S White
Demonstration of three-dimensional all-solid-state Li-ion batteries (3D SSLIBs) has been a long-standing goal for numerous researchers in the battery community interested in developing high power and high areal energy density storage solutions for a variety of applications. Ideally, the 3D geometry maximizes the volume of active material per unit area, while keeping its thickness small to allow for fast Li diffusion. In this paper, we describe experimental testing and simulation of 3D SSLIBs fabricated using materials and thin-film deposition methods compatible with semiconductor device processing...
November 30, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27910855/l-type-calcium-channels-regulate-filopodia-stability-and-cancer-cell-invasion-downstream-of-integrin-signalling
#18
Guillaume Jacquemet, Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska
Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src...
December 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27883227/preterm-infants-exhibited-less-pain-during-a-heel-stick-when-they-were-played-the-same-music-their-mothers-listened-to-during-pregnancy
#19
Lina Kurdahi Badr, Taline Demerjian, Tania Daaboul, Hanan Abbas, Mirvat Hasan Zeineddine, Lama Charafeddine
AIM: Playing music during painful procedures has shown inconsistent benefits for preterm infants. This study observed preterm infants during a heel stick procedure to assess whether listening to the music their mothers listened to during pregnancy had any impact on their pain and physiological and behavioural parameters. METHODS: We randomly exposed 42 preterm infants, with a mean gestational age of 31.8 ± 2.79 weeks, to the music their mothers listened to during pregnancy, recorded lullabies and no music, before, during and after a heel stick...
November 24, 2016: Acta Paediatrica
https://www.readbyqxmd.com/read/27874238/li-ion-synaptic-transistor-for-low-power-analog-computing
#20
Elliot J Fuller, Farid El Gabaly, François Léonard, Sapan Agarwal, Steven J Plimpton, Robin B Jacobs-Gedrim, Conrad D James, Matthew J Marinella, A Alec Talin
Nonvolatile redox transistors (NVRTs) based upon Li-ion battery materials are demonstrated as memory elements for neuromorphic computer architectures with multi-level analog states, "write" linearity, low-voltage switching and low power dissipation. Simulations of backpropagation using the device properties reaches ideal classification accuracy. Physics-based simulations predict energy costs per "write" operation of <10 aJ when scaled to 200 × 200 nm.
November 22, 2016: Advanced Materials
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