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https://www.readbyqxmd.com/read/28337468/comparative-analysis-data-of-sf1-and-sf2-helicases-from-three-domains-of-life
#1
Wafi Chaar, Hiba Ibrahim, Juliana Kozah, Hala Chamieh
SF1 and SF2 helicases are important molecular motors that use the energy of ATP to unwind nucleic acids or nucleic-acid protein complexes. They are ubiquitous enzymes and found in almost all organisms sequenced to date. This article provides a comparative analysis for SF1 and SF2 helicase families from three domains of life archaea, human, bacteria. Seven families are conserved in these three representatives and includes Upf1-like, UvrD-like, Rad3-like, DEAD-box, RecQ-like. Snf2 and Ski2-like. The data highlight conservation of the helicase core motifs for each of these families...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28336609/transition-from-turbulent-to-coherent-flows-in-confined-three-dimensional-active-fluids
#2
Kun-Ta Wu, Jean Bernard Hishamunda, Daniel T N Chen, Stephen J DeCamp, Ya-Wen Chang, Alberto Fernández-Nieves, Seth Fraden, Zvonimir Dogic
Transport of fluid through a pipe is essential for the operation of macroscale machines and microfluidic devices. Conventional fluids only flow in response to external pressure. We demonstrate that an active isotropic fluid, composed of microtubules and molecular motors, autonomously flows through meter-long three-dimensional channels. We establish control over the magnitude, velocity profile, and direction of the self-organized flows and correlate these to the structure of the extensile microtubule bundles...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28334866/c9orf72-and-rab7l1-regulate-vesicle-trafficking-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#3
Yoshitsugu Aoki, Raquel Manzano, Yi Lee, Ruxandra Dafinca, Misako Aoki, Andrew G L Douglas, Miguel A Varela, Chaitra Sathyaprakash, Jakub Scaber, Paola Barbagallo, Pieter Vader, Imre Mäger, Kariem Ezzat, Martin R Turner, Naoki Ito, Samanta Gasco, Norihiko Ohbayashi, Samir El Andaloussi, Shin'ichi Takeda, Mitsunori Fukuda, Kevin Talbot, Matthew J A Wood
A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#4
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28329908/re-evaluating-the-roles-of-myosin-18a%C3%AE-and-f-actin-in-determining-golgi-morphology
#5
Kyle Bruun, Jordan R Beach, Sarah M Heissler, Kirsten Remmert, James R Sellers, John A Hammer
The peri-centrosomal localization and morphology of the Golgi apparatus depends largely on the microtubule cytoskeleton and the microtubule motor protein dynein. Recent studies proposed that myosin 18Aα (M18Aα) also contributes to Golgi morphology by binding the Golgi protein GOLPH3 and walking along adjacent actin filaments to stretch the Golgi into its classic ribbon structure. Biochemical analyses have shown, however, that M18A is not an actin-activated ATPase and lacks motor activity. Our goal, therefore, was to define the precise molecular mechanism by which M18Aα determines Golgi morphology...
March 22, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/28324302/huntington-s-disease-update-on-treatments
#6
REVIEW
Kara J Wyant, Andrew J Ridder, Praveen Dayalu
Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, ending in death. Despite the discovery of the underlying genetic mutation more than 20 years ago, treatment remains focused on symptomatic management. Chorea, the most recognizable symptom, responds to medication that reduces dopaminergic neurotransmission. Psychiatric symptoms such as depression and anxiety may also respond well to symptomatic therapies...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28324299/fatal-familial-insomnia-clinical-aspects-and-molecular-alterations
#7
REVIEW
Franc Llorens, Juan-José Zarranz, Andre Fischer, Inga Zerr, Isidro Ferrer
PURPOSE OF REVIEW: Fatal familiar insomnia (FFI) is an autosomal dominant inherited prion disease caused by D178N mutation in the prion protein gene (PRNP D178N) accompanied by the presence of a methionine at the codon 129 polymorphic site on the mutated allele. FFI is characterized by severe sleep disorder, dysautonomia, motor signs and abnormal behaviour together with primary atrophy of selected thalamic nuclei and inferior olives, and expansion to other brain regions with disease progression...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28321933/exploring-the-cause-of-aggregation-and-reduced-zn-binding-affinity-by-g85r-mutation-in-sod1-rendering-amyotrophic-lateral-sclerosis
#8
E Srinivasan, R Rajasekaran
Amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disorder is characterized by the degeneration of upper and lower motor neuron. ALS occurs due to various notably prominent missense mutations, in gene encoding Cu-Zn superoxide dismutase (SOD1) thereby leading to aggregation, dysfunction and reduced Zn binding affinity. In this study, one such mutation, G85R was explored in comparison with wild type SOD1, using discrete molecular dynamics (DMD). Accordingly, the conformational changes were significantly observed in mutant SOD1, through various geometrical parameters, which substantiated the difference in conformational deviation, flexibility and compactness, thus stipulating a root cause for aggregation...
March 21, 2017: Proteins
https://www.readbyqxmd.com/read/28320824/molecular-mechanism-of-dynein-recruitment-to-kinetochores-by-the-rod-zw10-zwilch-complex-and-spindly
#9
José B Gama, Cláudia Pereira, Patrícia A Simões, Ricardo Celestino, Rita M Reis, Daniel J Barbosa, Helena R Pires, Cátia Carvalho, João Amorim, Ana X Carvalho, Dhanya K Cheerambathur, Reto Gassmann
The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal β-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod β-propeller-Zwilch complex in vitro...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28319616/dna-probes-for-monitoring-dynamic-and-transient-molecular-encounters-on-live-cell-membranes
#10
Mingxu You, Yifan Lyu, Da Han, Liping Qiu, Qiaoling Liu, Tao Chen, Cuichen Sam Wu, Lu Peng, Liqin Zhang, Gang Bao, Weihong Tan
Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals...
March 20, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28319615/dual-light-control-of-nanomachines-that-integrate-motor-and-modulator-subunits
#11
Justin T Foy, Quan Li, Antoine Goujon, Jean-Rémy Colard-Itté, Gad Fuks, Emilie Moulin, Olivier Schiffmann, Damien Dattler, Daniel P Funeriu, Nicolas Giuseppone
A current challenge in the field of artificial molecular machines is the synthesis and implementation of systems that can produce useful work when fuelled with a constant source of external energy. The first experimental achievements of this kind consisted of machines with continuous unidirectional rotations and translations that make use of 'Brownian ratchets' to bias random motions. An intrinsic limitation of such designs is that an inversion of directionality requires heavy chemical modifications in the structure of the actuating motor part...
March 20, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28315782/human-comt-over-expression-confers-a-heightened-susceptibility-to-dyskinesia-in-mice
#12
Oscar Solís, Jose-Rubén García-Montes, Patricia Garcia-Sanz, Antonio S Herranz, Maria-José Asensio, Gina Kang, Noboru Hiroi, Rosario Moratalla
Catechol-O-methyltransferase (COMT) degrades dopamine and its precursor l-DOPA and plays a critical role in regulating synaptic dopamine actions. We investigated the effects of heightened levels of COMT on dopamine-regulated motor behaviors and molecular alterations in a mouse model of dyskinesia. Transgenic mice overexpressing human COMT (TG) and their wildtype (WT) littermates received unilateral 6-OHDA lesions in the dorsal striatum and were treated chronically with l-DOPA for two weeks. l-DOPA-induced dyskinesia was exacerbated in TG mice without altering l-DOPA motor efficacy as determined by contralateral rotations or motor coordination...
March 16, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28315276/the-sigma-1-receptor-a-therapeutic-target-for-the-treatment-of-als
#13
Timur A Mavlyutov, Erin M Baker, Tasher M Losenegger, Jaimie R Kim, Brian Torres, Miles L Epstein, Arnold E Ruoho
The membrane bound 223 amino acid Sigma-1 Receptor (S1R) serves as a molecular chaperone and functional regulator of many signaling proteins. Spinal cord motor neuron activation occurs, in part, via large ventral horn cholinergic synapses called C-boutons/C-terminals. Chronic excitation of motor neurons and alterations in C-terminals has been associated with Amyotrophic Lateral Sclerosis (ALS ). The S1R has an important role in regulating motor neuron function. High levels of the S1R are localized in postsynaptic endoplasmic reticulum (ER) subsurface cisternae within 10-20 nm of the plasma membrane that contain muscarinic type 2 acetylcholine receptors (M2AChR), calcium activated potassium channels (Kv2...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315072/direct-myosin-activation-by-omecamtiv-mecarbil-for-heart-failure-with-reduced-ejection-fraction
#14
Mitchell A Psotka, John R Teerlink
Myosin is the indispensable molecular motor that utilizes chemical energy to produce force for contraction within the cardiac myocyte. Myosin activity is gated by intracellular calcium levels which are regulated by multiple upstream signaling cascades that can be altered for clinical utility using inotropic medications. In contrast to clinically available cardiac inotropes, omecamtiv mecarbil is a novel direct myosin activator developed to augment left ventricular systolic function without the undesirable secondary effects of altered calcium homeostasis...
March 18, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28302912/intraflagellar-transport-protein-ift52-recruits-ift46-to-the-basal-body-and-flagella
#15
Bo Lv, Lei Wan, Michael Taschner, Xi Cheng, Esben Lorentzen, Kaiyao Huang
Cilia are microtubule based organelles and perform motile, sensing and signaling functions. The assembly and maintenance of cilia depend on intraflagellar transport. Besides ciliary localization, most IFT proteins accumulate at basal bodies. However, little is known about the molecular mechanism of basal body targeting of IFT proteins. We first identified the possible basal body targeting sequence of IFT46 by expressing IFT46 truncations in ift46-1 mutant. The C-terminal sequence 246-321 aa, termed BBTS3, was sufficient to target YFPs to basal bodies in ift46-1 Interestingly, BBTS3 is also responsible for the ciliary targeting of IFT46...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302907/skip-controls-lysosome-positioning-using-a-composite-kinesin-1-heavy-and-light-chain-binding-domain
#16
Anneri Sanger, Yan Y Yip, Thomas S Randall, Stefano Pernigo, Roberto A Steiner, Mark P Dodding
The molecular interplay between cargo recognition and regulation of the activity of the kinesin-1 microtubule motor is not well understood. Using the lysosome adaptor SKIP as model cargo, we show that the heavy chains (KHCs), in addition to the light chains (KLCs), can recognize tryptophan-acidic binding determinants on the cargo when presented in the context of an extended KHC interacting domain. Mutational separation of KHC and KLC binding shows that both interactions are important for SKIP-kinesin-1 interaction in vitro and that KHC binding is important for lysosome transport in vivo...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28297971/sufficient-conditions-for-the-additivity-of-stall-forces-generated-by-multiple-filaments-or-motors
#17
Tripti Bameta, Dipjyoti Das, Dibyendu Das, Ranjith Padinhateeri, Mandar M Inamdar
Molecular motors and cytoskeletal filaments work collectively most of the time under opposing forces. This opposing force may be due to cargo carried by motors or resistance coming from the cell membrane pressing against the cytoskeletal filaments. Some recent studies have shown that the collective maximum force (stall force) generated by multiple cytoskeletal filaments or molecular motors may not always be just a simple sum of the stall forces of the individual filaments or motors. To understand this excess or deficit in the collective force, we study a broad class of models of both cytoskeletal filaments and molecular motors...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28297930/analysis-of-spontaneous-oscillations-for-a-three-state-power-stroke-model
#18
Takumi Washio, Toshiaki Hisada, Seine A Shintani, Hideo Higuchi
Our study considers the mechanism of the spontaneous oscillations of molecular motors that are driven by the power stroke principle by applying linear stability analysis around the stationary solution. By representing the coupling equation of microscopic molecular motor dynamics and mesoscopic sarcomeric dynamics by a rank-1 updated matrix system, we derived the analytical representations of the eigenmodes of the Jacobian matrix that cause the oscillation. Based on these analytical representations, we successfully derived the essential conditions for the oscillation in terms of the rate constants of the power stroke and the reversal stroke transitions of the molecular motor...
February 2017: Physical Review. E
https://www.readbyqxmd.com/read/28297650/rotation-mechanism-of-molecular-motor-v1-atpase-studied-by-multiscale-molecular-dynamics-simulation
#19
Yuta Isaka, Toru Ekimoto, Yuichi Kokabu, Ichiro Yamato, Takeshi Murata, Mitsunori Ikeguchi
Enterococcus hirae V1-ATPase is a molecular motor composed of the A3B3 hexamer ring and the central stalk. In association with ATP hydrolysis, three catalytic AB pairs in the A3B3 ring undergo conformational changes, which lead to a 120° rotation of the central stalk. To understand how the conformational changes of three catalytic pairs induce the 120° rotation of the central stalk, we performed multiscale molecular dynamics (MD) simulations in which coarse-grained and all-atom MD simulations were combined using a fluctuation matching methodology...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28294431/fluorine-substituted-molecular-motors-with-a-quaternary-stereogenic-center
#20
Peter Štacko, Jos C M Kistemaker, Ben Lucas Feringa
A series of unprecedented second generation molecular motors featuring a quaternary stereogenic center substituted with a fluorine atom has been synthesized. It is demonstrated that a seemingly benign replacement of the stereogenic hydrogen for a fluorine atom, regarded as a common substituent in pharmacology, resulted in a dramatic change in the energetic profile of thermal helix inversion. The barrier for the thermal helix inversion was found to increase considerably (by 20-30 kJ·mol-1), presumably due to destabilization of the transition state by increased steric hindrance when the fluorine atom is forced to pass over the lower half of the motor...
March 15, 2017: Chemistry: a European Journal
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