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https://www.readbyqxmd.com/read/28593744/thermosensitive-heparin-poloxamer-hydrogels-enhance-the-effects-of-gdnf-on-neuronal-circuit-remodelling-and-neuroprotection-after-spinal-cord-injury
#1
Ying-Zheng Zhao, Xi Jiang, Qian Lin, He-Lin Xu, Ya-Dong Huang, Cui-Tao Lu, Jun Cai
Traumatic spinal cord injury (SCI) results in paraplegia or quadriplegia, and currently, therapeutic interventions for axonal regeneration after SCI are not clinically available. Animal studies have revealed that glial cell-derived neurotrophic factor (GDNF) plays multiple beneficial roles in neuroprotection, glial scarring remodelling, axon regeneration and remyelination in SCI. However, the poor physicochemical stability of GDNF, as well as its limited ability to cross the blood-spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice...
June 7, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28572509/dynamic-distinctions-in-the-sodium-calcium-exchanger-adopting-the-inward-and-outward-facing-conformational-states
#2
Moshe Giladi, Liat van Dijk, Bosmat Refaeli, Lior Almagor, Reuben Hiller, Petr Man, Eric Forest, Daniel Khananshvili
Na(+)/Ca(2+) exchanger (NCX) proteins operate through the alternating access mechanism, where the ion-binding pocket is exposed in succession either to the extracellular or the intracellular face of the membrane. The archaeal NCX_Mj (Methanococcus jannaschii NCX) system was used to resolve the backbone dynamics in the inward facing (IF) and outward-facing (OF) states by analyzing purified preparations of apo and ion-bound forms of NCX_Mj-WT and its mutant, NCX_Mj-5L6-8. First, the exposure of extracellular and cytosolic vestibules to the bulk phase was evaluated as the reactivity of single cysteine-mutants to a fluorescent probe, verifying that NCX_Mj-WT and NCX_Mj-5L6-8 preferentially adopt the OF and IF states, respectively...
June 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28514446/identification-of-preoptic-sleep-neurons-using-retrograde-labelling-and-gene-profiling
#3
Shinjae Chung, Franz Weber, Peng Zhong, Chan Lek Tan, Thuc Nghi Nguyen, Kevin T Beier, Nikolai Hörmann, Wei-Cheng Chang, Zhe Zhang, Johnny Phong Do, Shenqin Yao, Michael J Krashes, Bosiljka Tasic, Ali Cetin, Hongkui Zeng, Zachary A Knight, Liqun Luo, Yang Dan
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep...
May 25, 2017: Nature
https://www.readbyqxmd.com/read/28490179/-living-dynamics-of-filamentous-bacteria-on-an-adherent-surface-under-hydrodynamic-exposure
#4
Justin P Jahnke, Austin M Smith, Nicole E Zander, Victoria Wiedorn, Kenneth E Strawhecker, Jessica L Terrell, Dimitra N Stratis-Cullum, Xuanhong Cheng
The potential advantages of cell-based biohybrid devices over conventional nonliving systems drive the interest to control the behavior of the underlying biological cells in microdevices. Here, the authors studied how shear influenced the geometry and elongation of fimbriated filaments on affinity substrates. The cells were engineered to express FimH, which binds to mannose with a high affinity. A microfluidic channel was functionalized with RNAse B, which is rich in mannose residues, and the device was used to control the hydrodynamic force on live Escherichia coli under filamentous growth...
May 10, 2017: Biointerphases
https://www.readbyqxmd.com/read/28364042/kinetic-based-trapping-by-intervening-sequence-variants-of-the-active-sites-of-protein-disulfide-isomerase-identifies-platelet-protein-substrates
#5
Jack D Stopa, Katherine M Baker, Steven P Grover, Robert Flaumenhaft, Bruce Furie
Thiol isomerases such as protein-disulfide isomerase (PDI) direct disulfide rearrangements required for proper folding of nascent proteins synthesized in the endoplasmic reticulum. Identifying PDI substrates is challenging because PDI catalyzes conformational changes that cannot be easily monitored (e.g. compared with proteolytic cleavage or amino acid phosphorylation); PDI has multiple substrates; and it can catalyze either oxidation, reduction, or isomerization of substrates. Kinetic-based substrate trapping wherein the active site motif CGHC is modified to CGHA to stabilize a PDI-substrate intermediate is effective in identifying some substrates...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27581987/imperfect-symmetry-of-sp1-and-core-promoter-sequences-regulates-early-and-late-virus-gene-expression-of-the-bidirectional-bk-polyomavirus-noncoding-control-region
#6
Tobias Bethge, Elvis Ajuh, Hans H Hirsch
Rearrangements or point mutations in the noncoding control region (NCCR) of BK polyomavirus (BKPyV) have been associated with higher viral loads and more pronounced organ pathology in immunocompromised patients. The respective alterations affect a multitude of transcription factor binding sites (TFBS) but consistently cause increased expression of the early viral gene region (EVGR) at the expense of late viral gene region (LVGR) expression. By mutating TFBS, we identified three phenotypic groups leading to strong, intermediate, or impaired EVGR expression and corresponding BKPyV replication...
November 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27280685/%C3%AE-synuclein-binds-to-tom20-and-inhibits-mitochondrial-protein-import-in-parkinson-s-disease
#7
Roberto Di Maio, Paul J Barrett, Eric K Hoffman, Caitlyn W Barrett, Alevtina Zharikov, Anupom Borah, Xiaoping Hu, Jennifer McCoy, Charleen T Chu, Edward A Burton, Teresa G Hastings, J Timothy Greenamyre
α-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be related. Mitochondrial dysfunction leads to accumulation and oligomerization of α-synuclein, and increased levels of α-synuclein cause mitochondrial impairment, but the basis for this bidirectional interaction remains obscure. We now report that certain posttranslationally modified species of α-synuclein bind with high affinity to the TOM20 (translocase of the outer membrane 20) presequence receptor of the mitochondrial protein import machinery...
June 8, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27136113/spatial-separation-of-replisome-arrest-sites-influences-homologous-recombination-quality-at-a-tus-ter-mediated-replication-fork-barrier
#8
Nicholas A Willis, Ralph Scully
The Escherichia coli replication fork arrest complex Tus/Ter mediates site-specific replication fork arrest and homologous recombination (HR) on a mammalian chromosome, inducing both conservative "short tract" gene conversion (STGC) and error-prone "long tract" gene conversion (LTGC) products. We showed previously that bidirectional fork arrest is required for the generation of STGC products at Tus/Ter-stalled replication forks and that the HR mediators BRCA1, BRCA2 and Rad51 mediate STGC but suppress LTGC at Tus/Ter-arrested forks...
July 17, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27122038/neurotrophin-3-regulates-synapse-development-by-modulating-trkc-ptp%C3%AF-synaptic-adhesion-and-intracellular-signaling-pathways
#9
Kyung Ah Han, Doyeon Woo, Seungjoon Kim, Gayoung Choii, Sangmin Jeon, Seoung Youn Won, Ho Min Kim, Won Do Heo, Ji Won Um, Jaewon Ko
UNLABELLED: Neurotrophin-3 (NT-3) is a secreted neurotrophic factor that binds neurotrophin receptor tyrosine kinase C (TrkC), which in turn binds to presynaptic protein tyrosine phosphatase σ (PTPσ) to govern excitatory synapse development. However, whether and how NT-3 cooperates with the TrkC-PTPσ synaptic adhesion pathway and TrkC-mediated intracellular signaling pathways in rat cultured neurons has remained unclear. Here, we report that NT-3 enhances TrkC binding affinity for PTPσ...
April 27, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26539440/insights-into-the-molecular-mechanism-of-allostery-in-hsp70s
#10
REVIEW
Matthias P Mayer, Roman Kityk
Hsp70s chaperone an amazing number and variety of cellular protein folding processes. Key to their versatility is the recognition of a short degenerate sequence motif, present in practically all polypeptides, and a bidirectional allosteric intramolecular regulation mechanism linking their N-terminal nucleotide binding domain (NBD) and their C-terminal polypeptide substrate binding domain (SBD). Through this interdomain communication ATP binding to the NBD and ATP hydrolysis control the affinity of the SBD for polypeptide substrates and substrate binding to the SBD triggers ATP hydrolysis...
2015: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/26526814/flowers-of-the-early-branching-papilionoid-legume-petaladenium-urceoliferum-display-unique-morphological-and-ontogenetic-features
#11
Gerhard Prenner, Domingos Cardoso, Charles E Zartman, Luciano P de Queiroz
PREMISE OF THE STUDY: Floral development can help to shed light on puzzling features across flowering plants. The enigmatic Amazonian monospecific genus Petaladenium of the legume family (Leguminosae) had rarely been collected and only recently became available for ontogenetic studies. The fimbriate-glandular wing petals of P. urceoliferum are unique among the more than 19000 legume species. Ontogenetic data illuminate the systematic position of the genus and foster our understanding on floral evolution during the early diversification of the papilionoid legumes...
November 2015: American Journal of Botany
https://www.readbyqxmd.com/read/26435028/bidirectional-effects-of-dexmedetomidine-on-human-platelet-functions-in-vitro
#12
Shuji Kawamoto, Hideo Hirakata, Naoko Sugita, Kazuhiko Fukuda
Platelets express the imidazoline (I)-receptor, I1 and I2, as well as the α2-adrenoceptor. Although dexmedetomidine, a selective α2-adrenoceptor agonist with some affinity for the I-receptor is expected to affect platelet function, the effects of dexmedetomidine on platelet functions remain unclear. In the present study, we investigated the effects of dexmedetomidine on human platelet functions in vitro. The effects of dexmedetomidine on platelet aggregation were examined using aggregometers. The formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in platelets was measured by an enzyme immunoassay...
November 5, 2015: European Journal of Pharmacology
https://www.readbyqxmd.com/read/26382577/optical-mapping-of-intra-sarcoplasmic-reticulum-ca2-and-transmembrane-potential-in-the-langendorff-perfused-rabbit-heart
#13
Lianguo Wang, Nicole M De Jesus, Crystal M Ripplinger
Sarcoplasmic reticulum (SR) Ca2+ handling plays a key role in normal excitation-contraction coupling and aberrant SR Ca2+ handling is known to play a significant role in certain types of arrhythmia. Because arrhythmias are spatially distinct, emergent phenomena, they must be investigated at the tissue level. However, methods for directly probing SR Ca2+ in the intact heart remain limited. This article describes the protocol for dual optical mapping of transmembrane potential (Vm) and free intra-SR [Ca2+] ([Ca2+]SR) in the Langendorff-perfused rabbit heart...
September 10, 2015: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/26356009/rerouting-electron-transfer-in-molecular-assemblies-by-redox-pair-matching
#14
Renata Balgley, Sreejith Shankar, Michal Lahav, Milko E van der Boom
We demonstrate how the distance over which electron transfer occurs through organic materials can be controlled and extended. Coating of conductive surfaces with nanoscale layers of redox-active metal complexes allows the electrochemical addressing of distant layers that are otherwise electrochemically silent. Our materials can pass electrons selectively in directions that are determined by positioning of layers of metal complexes and the distances between them. These electron-transfer processes can be made dominantly uni- or bidirectional...
October 12, 2015: Angewandte Chemie
https://www.readbyqxmd.com/read/26235970/nonlinear-dynamics-in-the-perceptual-grouping-of-connected-surfaces
#15
Howard S Hock, Gregor Schöner
Evidence obtained using the dynamic grouping method has shown that the grouping of an object's connected surfaces has properties characteristic of a nonlinear dynamical system. When a surface's luminance changes, one of its boundaries is perceived moving across the surface. The direction of this dynamic grouping (DG) motion indicates which of two flanking surfaces has been grouped with the changing surface. A quantitative measure of overall grouping strength (affinity) for adjacent surfaces is provided by the frequency of DG motion perception in directions promoted by the grouping variables...
September 2016: Vision Research
https://www.readbyqxmd.com/read/26189062/regulation-of-integrin-mediated-adhesions
#16
REVIEW
Daniel V Iwamoto, David A Calderwood
Integrins are heterodimeric transmembrane adhesion receptors that couple the actin cytoskeleton to the extracellular environment and bidirectionally relay signals across the cell membrane. These processes are critical for cell attachment, migration, differentiation, and survival, and therefore play essential roles in metazoan development, physiology, and pathology. Integrin-mediated adhesions are regulated by diverse factors, including the conformation-specific affinities of integrin receptors for their extracellular ligands, the clustering of integrins and their intracellular binding partners into discrete adhesive structures, mechanical forces exerted on the adhesion, and the intracellular trafficking of integrins themselves...
October 2015: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/26119475/elevated-non-esterified-fatty-acid-concentrations-hamper-bovine-oviductal-epithelial-cell-physiology-in-three-different-in-vitro-culture-systems
#17
L Jordaens, M Arias-Alvarez, I Pintelon, S Thys, S Valckx, Y Dezhkam, P E J Bols, J L M R Leroy
Elevated non-esterified fatty acids (NEFAs) have been recognized as an important link between lipolytic metabolic conditions and impaired fertility in high-yielding dairy cows. However, NEFA effects on the oviductal micro-environment currently remain unknown. We hypothesize that elevated NEFAs may contribute to the complex pathology of subfertility by exerting a negative effect on bovine oviductal epithelial cell (BOEC) physiology. Therefore, the objectives of this study were to elucidate direct NEFA effects on BOEC physiology in three different in vitro cell culture systems...
October 1, 2015: Theriogenology
https://www.readbyqxmd.com/read/25727331/isolation-of-integrin-based-adhesion-complexes
#18
Matthew C Jones, Jonathan D Humphries, Adam Byron, Angélique Millon-Frémillon, Joseph Robertson, Nikki R Paul, Daniel H J Ng, Janet A Askari, Martin J Humphries
The integration of cells with their extracellular environment is facilitated by cell surface adhesion receptors, such as integrins, which play important roles in both normal development and the onset of pathologies. Engagement of integrins with their ligands in the extracellular matrix, or counter-receptors on other cells, initiates the intracellular assembly of a wide variety of proteins into adhesion complexes such as focal contacts, focal adhesions, and fibrillar adhesions. The proteins recruited to these complexes mediate bidirectional signaling across the plasma membrane, and, as such, help to coordinate and/or modulate the multitude of physical and chemical signals to which the cell is subjected...
March 2, 2015: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/25724910/quantitative-proteomics-reveals-protein-protein-interactions-with-fibroblast-growth-factor-12-as-a-component-of-the-voltage-gated-sodium-channel-1-2-nav1-2-macromolecular-complex-in-mammalian-brain
#19
Norelle C Wildburger, Syed R Ali, Wei-Chun J Hsu, Alexander S Shavkunov, Miroslav N Nenov, Cheryl F Lichti, Richard D LeDuc, Ekaterina Mostovenko, Neli I Panova-Elektronova, Mark R Emmett, Carol L Nilsson, Fernanda Laezza
Voltage-gated sodium channels (Nav1.1-Nav1.9) are responsible for the initiation and propagation of action potentials in neurons, controlling firing patterns, synaptic transmission and plasticity of the brain circuit. Yet, it is the protein-protein interactions of the macromolecular complex that exert diverse modulatory actions on the channel, dictating its ultimate functional outcome. Despite the fundamental role of Nav channels in the brain, information on its proteome is still lacking. Here we used affinity purification from crude membrane extracts of whole brain followed by quantitative high-resolution mass spectrometry to resolve the identity of Nav1...
May 2015: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/25721438/a-lysinated-thiophene-based-semiconductor-as-a-multifunctional-neural-bioorganic-interface
#20
Simone Bonetti, Assunta Pistone, Marco Brucale, Saskia Karges, Laura Favaretto, Massimo Zambianchi, Tamara Posati, Anna Sagnella, Marco Caprini, Stefano Toffanin, Roberto Zamboni, Nadia Camaioni, Michele Muccini, Manuela Melucci, Valentina Benfenati
Lysinated molecular organic semiconductors are introduced as valuable multifunctional platforms for neural cells growth and interfacing. Cast films of quaterthiophene (T4) semiconductor covalently modified with lysine-end moieties (T4Lys) are fabricated and their stability, morphology, optical/electrical, and biocompatibility properties are characterized. T4Lys films exhibit fluorescence and electronic transport as generally observed for unsubstituted oligothiophenes combined to humidity-activated ionic conduction promoted by the charged lysine-end moieties...
June 3, 2015: Advanced Healthcare Materials
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