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https://www.readbyqxmd.com/read/27927783/spectral-and-spatial-tuning-of-onset-and-offset-response-functions-in-auditory-cortical-fields-a1-and-cl-of-rhesus-macaques
#1
Deepa L Ramamurthy, Gregg H Recanzone
The mammalian auditory cortex is necessary for spectral and spatial processing of acoustic stimuli. Most physiological studies of single neurons in the auditory cortex have focused on the onset and sustained portions of evoked responses, but there have been far fewer studies on the relationship between onset and offset responses. In the current study, we compared spectral and spatial tuning of onset and offset responses of neurons in primary auditory cortex (A1) and the caudolateral (CL) belt area of awake macaque monkeys...
December 7, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#2
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27924919/a-central-cavity-within-the-holo-translocon-suggests-a-mechanism-for-membrane-protein-insertion
#3
Mathieu Botte, Nathan R Zaccai, Jelger Lycklama À Nijeholt, Remy Martin, Kèvin Knoops, Gabor Papai, Juan Zou, Aurélien Deniaud, Manikandan Karuppasamy, Qiyang Jiang, Abhishek Singha Roy, Klaus Schulten, Patrick Schultz, Juri Rappsilber, Giuseppe Zaccai, Imre Berger, Ian Collinson, Christiane Schaffitzel
The conserved SecYEG protein-conducting channel and the accessory proteins SecDF-YajC and YidC constitute the bacterial holo-translocon (HTL), capable of protein-secretion and membrane-protein insertion. By employing an integrative approach combining small-angle neutron scattering (SANS), low-resolution electron microscopy and biophysical analyses we determined the arrangement of the proteins and lipids within the super-complex. The results guided the placement of X-ray structures of individual HTL components and allowed the proposal of a model of the functional translocon...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920897/impact-of-biopolymer-matrices-on-relaxometric-properties-of-contrast-agents
#4
Alfonso Maria Ponsiglione, Maria Russo, Paolo Antonio Netti, Enza Torino
Properties of water molecules at the interface between contrast agents (CAs) for magnetic resonance imaging and macromolecules could have a valuable impact on the effectiveness of metal chelates. Recent studies, indeed, demonstrated that polymer architectures could influence CAs' relaxivity by modifying the correlation times of the metal chelate. However, an understanding of the physico-chemical properties of polymer/CA systems is necessary to improve the efficiency of clinically used CAs, still exhibiting low relaxivity...
December 6, 2016: Interface Focus
https://www.readbyqxmd.com/read/27919007/challenges-in-assignment-of-allosteric-effects-in-cytochrome-p450-catalyzed-substrate-oxidations-to-structural-dynamics-in-the-hemoprotein-architecture
#5
Peter Hlavica
Cytochrome P450s (CYP) represent a superfamily of b-type hemoproteins catalyzing NAD(P)H-dependent oxidative biotransformation of a vast array of natural and xenobiotic compounds. Many eu- and prokaryotic members of this class of monooxygenases display complex non-Michaelis-Menten saturation kinetics, suggestive of homo-/heterotropic cooperativity arising from substrate-/effector-induced allosteric interactions. Here, the paradigm of multiple-ligand occupancy of the catalytic pocket in combination with enzyme oligomerization provides the most favored explanations for the atypical kinetic patterns...
November 25, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27917684/the-long-term-effect-of-oral-isotretinoin-therapy-on-macula-ganglion-cell-complex-thickness
#6
Gülizar Demirok, Yasemin Topalak, Özge Gündüz, Dilsun Yıldırım, Mehmet Fatih Kocamaz, Ahmet Sengun
PURPOSE: To evaluate the long term effect of oral isotretinoin therapy on macula ganglion cell complex (GCC) thickness by spectral domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Newly diagnosed cystic acne patients who received low dose for a long time systemic isotretinoin therapy were included to study. Thorough ophthalmic evaluation and GCC thickness analysis by using SD-OCT were performed at baseline, and at 1, 3, 6, and 12 months of treatment...
December 4, 2016: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/27914010/recruitment-by-the-repressor-freud-1-of-histone-deacetylase-brg1-chromatin-remodeling-complexes-to-strengthen-htr1a-gene-repression
#7
Tatiana Souslova, Kim Mirédin, Anne M Millar, Paul R Albert
Five-prime repressor element under dual repression binding protein-1 (Freud-1)/CC2D1A is genetically linked to intellectual disability and implicated in neuronal development. Freud-1 represses the serotonin-1A (5-HT1A) receptor gene HTR1A by histone deacetylase (HDAC)-dependent or HDAC-independent mechanisms in 5-HT1A-negative (e.g., HEK-293) or 5-HT1A-expressing cells (SK-N-SH), respectively. To identify the underlying mechanisms, Freud-1-associated proteins were affinity-purified from HEK-293 nuclear extracts and members of the Brg1/SMARCCA chromatin remodeling and Sin3A-HDAC corepressor complexes were identified...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27906279/adaptive-multifocus-image-fusion-using-block-compressed-sensing-with-smoothed-projected-landweber-integration-in-the-wavelet-domain
#8
Unni V S, Deepak Mishra, G R K S Subrahmanyam
The need for image fusion in current image processing systems is increasing mainly due to the increased number and variety of image acquisition techniques. Image fusion is the process of combining substantial information from several sensors using mathematical techniques in order to create a single composite image that will be more comprehensive and thus more useful for a human operator or other computer vision tasks. This paper presents a new approach to multifocus image fusion based on sparse signal representation...
December 1, 2016: Journal of the Optical Society of America. A, Optics, Image Science, and Vision
https://www.readbyqxmd.com/read/27904784/high-foxred1-expression-predicted-good-prognosis-of-colorectal-cancer
#9
Weiqiang Fei, Shuiping Liu, Xiaotong Hu
The human FAD-dependent oxidoreductase domain containing 1 (FOXRED1) protein is reported as an assembly factor which promotes the correct assembly and stability of mitochondrial Complex I (CI). Alterations of mitochondrial CI might cause tumorigenesis and metastasis, but it's molecular mechanisms remain unclear. In this study, we selected 145 cases of colorectal cancer for immunohistochemistry to explore the role of FOXRED1 played in the tumor progression of colorectal cancer. The relationship between FOXRED1 expression and clinicopathological features of colorectal cancers was evaluated...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#10
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27901172/conformational-states-of-hamp-domains-interacting-with-sensory-rhodopsin-membrane-systems-an-integrated-all-atom-and-coarse-grained-molecular-dynamics-simulation-approach
#11
Bikash Ranjan Sahoo, Toshimichi Fujiwara
Understanding the downstream signaling mechanism of sensory rhodopsin and its cognate transducer complex (srII-htrII) has long been a challenge in the field of photoreceptor research. Here, an integration of all-atom and coarse-grained (CG) molecular dynamics (MD) simulations in different srII-htrII complex states is carried out. It is shown that the cytoplasmic four-helix HAMP dimer gives rise to a gear-box model interaction with discrete hydrophobic packing in Natronomonas pharaonis (Np). Structural analysis in all-atom and CG-MD reveals a stable conformational state in the physiological environment (323 K and 1...
November 30, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27901146/comparative-experimental-and-theoretical-study-of-the-rotational-excitation-of-co-by-collision-with-ortho-and-para-d2-molecules
#12
T Stoecklin, A Faure, P Jankowski, S Chefdeville, A Bergeat, C Naulin, S B Morales, M Costes
A joint crossed beam and quantum mechanical investigation of the rotationally inelastic collisions of CO with ortho- and para-D2 molecules is reported. A new 4D potential energy surface (PES) averaged over the ground vibrational states of D2 and CO is used to calculate the rovibrational bound states of the ortho-D2-CO complexes. Close coupling calculations are then performed in the rigid rotor approximation for ortho- and para-D2 colliding with CO for the experimentally investigated transition of CO (j = 0 → 1) and for collision energies ranging from 0...
November 30, 2016: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/27896130/studies-of-the-autoinhibitory-segment-comprising-residues-31-60-of-the-prodomain-of-pcsk9-possible-implications-for-the-mechanism-underlying-gain-of-function-mutations
#13
Lene Wierød, Jamie Cameron, Thea Bismo Strøm, Trond P Leren
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) at the cell surface and is internalized as a complex with the LDLR. In the acidic milieu of the sorting endosome, PCSK9 remains bound to the LDLR and prevents the LDLR from folding over itself to adopt a closed conformation. As a consequence, the LDLR fails to recycle back to the cell membrane. Even though it is the catalytic domain of PCSK9 that interacts with the LDLR at the cell surface, the structurally disordered segment consisting of residues 31-60 and which is rich in acidic residues, has a negative effect both on autocatalytic cleavage and on the activity of PCSK9 towards the LDLR...
December 2016: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/27889368/graph-quality-in-top-medical-journals
#14
Jennifer C Chen, Richelle J Cooper, Michael E McMullen, David L Schriger
STUDY OBJECTIVE: Well-designed graphs can portray complex data and relationships in ways that are easier to interpret and understand than text and tables. Previous investigations of reports of clinical research showed that graphs are underused and, when used, often depict summary statistics instead of the data distribution. This descriptive study aims to evaluate the quantity and quality of graphs in the current medical literature across a broad range of better journals. METHODS: We performed a cross-sectional survey of 10 randomly selected original research articles per journal from the 2012 issues of 20 highly cited journals...
November 23, 2016: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/27884142/dna-methylation-patterns-associated-with-oxidative-stress-in-an-ageing-population
#15
Åsa K Hedman, Mihkel Zilmer, Johan Sundström, Lars Lind, Erik Ingelsson
BACKGROUND: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease...
November 25, 2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/27883986/a-model-of-free-living-gait-a-factor-analysis-in-parkinson-s-disease
#16
Rosie Morris, Aodhán Hickey, Silvia Del Din, Alan Godfrey, Sue Lord, Lynn Rochester
INTRODUCTION: Gait is a marker of global health, cognition and falls risk. Gait is complex, comprised of multiple characteristics sensitive to survival, age and pathology. Due to covariance amongst characteristics, conceptual gait models have been established to reduce redundancy and aid interpretation. Previous models have been derived from laboratory gait assessments which are costly in equipment and time. Body-worn monitors (BWM) allow for free-living, low-cost and continuous gait measurement and produce similar covariant gait characteristics...
November 16, 2016: Gait & Posture
https://www.readbyqxmd.com/read/27881680/structures-and-short-linear-motif-of-disordered-transcription-factor-regions-provide-clues-to-the-interactome-of-the-cellular-hub-radical-induced-cell-death1
#17
Charlotte O'Shea, Lasse Staby, Sidsel Krogh Bendsen, Frederik Grønbæk Tidemand, Andreas Redsted, Martin Willemoës, Birthe B Kragelund, Karen Skriver
Intrinsically disordered protein regions (IDRs) lack a well-defined three-dimensional structure, but often facilitate key protein functions. Some interactions between IDRs and folded protein domains rely on short linear motifs (SLiMs). These motifs are challenging to identify, but once found can point to larger networks of interactions, such as with proteins that serve as hubs for essential cellular functions. The stress-associated plant protein Radical-Induced Cell Death1 (RCD1) is one such hub, interacting with many transcription factors via their flexible IDRs...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27881652/inhibition-of-human-cytomegalovirus-pul89-terminase-subunit-blocks-virus-replication-and-genome-cleavage
#18
Yan Wang, Lili Mao, Jayakanth Kankanala, Zhengqiang Wang, Robert J Geraghty
: Human cytomegalovirus terminase complex cleaves the concatemeric genomic DNA into unit lengths during genome packaging and particle assembly. This process is an attractive drug target because cleavage of concatemeric DNA is not required in mammalian cell DNA replication, indicating that drugs targeting the terminase complex could be safe and selective. One component of the human cytomegalovirus terminase complex, pUL89, provides the endonucleolytic activity for genome cleavage and the domain responsible is reported to have an RNase H-like fold...
November 23, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27876371/approaches-for-treatment-of-aortic-arch-aneurysm-a-numerical-study
#19
Asaph Nardi, Idit Avrahami
Aortic arch aneurysm is a complex pathology which requires coverage of one or more aortic arch vessels. In this study we explore the hemodynamic behavior of the aortic arch in aneurysmatic and treated cases with three currently available treatment approaches: Surgery Graft, hybrid Stent-Graft and chimney Stent Graft. The analysis included four models of the time-dependent fluid domains of aneurysmatic arch and of the surgery, hybrid and chimney endovascular techniques. Dimensions of the models are based on typical anatomy, and boundary conditions are based on typical physiological flow...
November 12, 2016: Journal of Biomechanics
https://www.readbyqxmd.com/read/27872875/a-comparison-of-the-innate-flexibilities-of-six-chains-in-f1-atpase-with-identical-secondary-and-tertiary-folds-3-active-enzymes-and-3-structural-proteins
#20
Monique M Tirion
The α and β subunits comprising the hexameric assembly of F1-ATPase share a high degree of structural identity, though low primary identity. Each subunit binds nucleotide in similar pockets, yet only β subunits are catalytically active. Why? We re-examine their internal symmetry axes and observe interesting differences. Dividing each chain into an N-terminal head region, a C-terminal foot region, and a central torso, we observe (1) that while the foot and head regions in all chains obtain high and similar mobility, the torsos obtain different mobility profiles, with the β subunits exhibiting a higher motility compared to the α subunits, a trend supported by the crystallographic B-factors...
July 2017: Structural Dynamics (Melville, N.Y.)
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