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https://www.readbyqxmd.com/read/27910992/tug-of-war-between-two-elastically-coupled-molecular-motors-a-case-study-on-force-generation-and-force-balance
#1
Mehmet Can Uçar, Reinhard Lipowsky
Intracellular transport is performed by molecular motors that pull cargos along cytoskeletal filaments. Many cellular cargos are observed to move bidirectionally, with fast transport in both directions. This behaviour can be understood as a stochastic tug-of-war between two teams of antagonistic motors. The first theoretical model for such a tug-of-war, the Müller-Klumpp-Lipowsky (MKL) model, was based on two simplifying assumptions: (i) both motor teams move with the same velocity in the direction of the stronger team, and (ii) this velocity matching and the associated force balance arise immediately after the rebinding of an unbound motor to the filament...
December 2, 2016: Soft Matter
https://www.readbyqxmd.com/read/27905041/new-xymedon-analogues-for-stimulation-of-posttraumatic-regeneration-of-the-spinal-cord-in-rats
#2
T V Povysheva, V E Semenov, I V Galyametdinova, V S Reznik, K S Knni, P E Kolesnikov, Yu A Chelyshev
Effect of systemic administration of synthetic pyrimidine derivatives, xymedon and compounds 29D and 34D, was studied in rats with experimental dosed contusion spinal cord injury. Xymedon promoted recovery of motor function after injury. Compounds 29D and 34D more effectively restored the parameters of open-field and Rotarod tests in comparison with xymedon. Compound 29D more effectively than xymedon maintained the number of Olig2(+) oligodendrocytes in the corticospinal tract and NG2 cells in all investigated areas of the white matter...
December 1, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27899296/targeting-the-norepinephrinergic-system-in-parkinson-s-disease-and-related-disorders-the-locus-coeruleus-story
#3
Yannick Vermeiren, Peter P De Deyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are related, progressive and debilitating neurodegenerative disorders with hallmark features that include a variety of motor and non-motor symptoms (behavioral, autonomic and cognitive dysfunction). For almost half a century, the motor aspects have been attributed to Lewy pathology (LP) predominantly in the substantia nigra (SN), causing a major loss of dopaminergic neurons. However, the relative success of dopaminergic replacement therapies for alleviation of solely the parkinsonian features has prompted researchers to further explore other monoaminergic strategies which may tackle all PD-related aspects...
November 26, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27894930/sex-dependent-influence-of-chronic-mild-stress-cms-on-voluntary-alcohol-consumption-study-of-neurobiological-consequences
#4
Eva M Marco, Javier Antonio Ballesta, Carlos Irala, María-Donina Hernández, María Elisa Serrano, Virginia Mela, Meritxell López-Gallardo, María-Paz Viveros
Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males...
November 25, 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27891785/editorial-brain-malformation-surveillance-in-the-zika-era
#5
EDITORIAL
Edwin Trevathan
The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection...
November 2016: Birth Defects Research. Part A, Clinical and Molecular Teratology
https://www.readbyqxmd.com/read/27891669/a-molecular-dynamics-study-of-the-binary-complexes-of-app-jip1-and-the-cargo-binding-domain-of-klc
#6
Cooper A Taylor, Bill R Miller, Soleil S Shah, Carol A Parish
Mutations in the amyloid precursor protein (APP) are responsible for the formation of amyloid-β peptides. These peptides play a role in Alzheimer's and other dementia-related diseases. The cargo binding domain of the kinesin-1 light chain motor protein (KLC1) may be responsible for transporting APP either directly or via interaction with C-jun N-terminal kinase-interacting protein 1 (JIP1). However, to date there has been no direct experimental or computational assessment of such binding at the atomistic level...
November 7, 2016: Proteins
https://www.readbyqxmd.com/read/27884703/mechanistic-and-biological-considerations-of-oxidatively-damaged-dna-for-helicase-dependent-pathways-of-nucleic-acid-metabolism
#7
Jack D Crouch, Robert M Brosh
Cells are under constant assault from reactive oxygen species that occur endogenously or arise from environmental agents. An important consequence of such stress is the generation of oxidatively damaged DNA, which is represented by a wide range of non-helix distorting and helix-distorting bulkier lesions that potentially affect a number of pathways including replication and transcription; consequently DNA damage tolerance and repair pathways are elicited to help cells cope with the lesions. The cellular consequences and metabolism of oxidatively damaged DNA can be quite complex with a number of DNA metabolic proteins and pathways involved...
November 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27881601/structural-basis-for-snrna-recognition-by-the-double-wd40-repeat-domain-of-gemin5
#8
Wenxing Jin, Yi Wang, Chao-Pei Liu, Na Yang, Mingliang Jin, Yao Cong, Mingzhu Wang, Rui-Ming Xu
Assembly of the spliceosomal small nuclear ribonucleoparticle (snRNP) core requires the participation of the multisubunit SMN (survival of motor neuron) complex, which contains SMN and several Gemin proteins. The SMN and Gemin2 subunits directly bind Sm proteins, and Gemin5 is required for snRNP biogenesis and has been implicated in snRNA recognition. The RNA sequence required for snRNP assembly includes the Sm site and an adjacent 3' stem-loop, but a precise understanding of Gemin5's RNA-binding specificity is lacking...
November 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27880015/bifunctional-molecular-photoswitches-based-on-overcrowded-alkenes-for-dynamic-control-of-catalytic-activity-in-michael-addition-reactions
#9
Stefano F Pizzolato, Beatrice S L Collins, Thomas van Leeuwen, Ben Lucas Feringa
The emerging field of artificial photoswitchable catalysis has recently shown striking examples of functional light-responsive systems allowing for dynamic control of activity and selectivity in organocatalysis and metal-catalysed transformations. While our group has already disclosed systems featuring first generation molecular motors as the switchable central core, a design based on second generation molecular motors is lacking. Herein, the syntheses of two bifunctionalized molecular switches based on a photoresponsive tetrasubstituted alkene core are reported...
November 23, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27877154/immununochemical-markers-of-the-amyloid-cascade-in-the-hippocampus-in-motor-neuron-diseases
#10
Ulises Gómez-Pinedo, Rocio N Villar-Quiles, Lucia Galán, Jordi A Matías-Guiu, Maria S Benito-Martin, Antonio Guerrero-Sola, Teresa Moreno-Ramos, Jorge Matías-Guiu
BACKGROUND: Several findings suggest that the amyloid precursor protein (APP) and the amyloid cascade may play a role in motor neuron disease (MND). OBJECTIVE: Considering that dementia is one of the most frequent non-motor symptoms in amyotrophic lateral sclerosis (ALS) and that hippocampus is one of the brain areas with greater presence of amyloid-related changes in neurodegenerative diseases, our aim was to analyze the molecular markers of the amyloid cascade of APP in pathology studies of the hippocampus of autopsied patients with ALS and ALS-frontotemporal dementia (FTD)...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27877114/ontogenetic-development-of-vestibulo-ocular-reflexes-in-amphibians
#11
REVIEW
Francisco Branoner, Boris P Chagnaud, Hans Straka
Vestibulo-ocular reflexes (VOR) ensure gaze stability during locomotion and passively induced head/body movements. In precocial vertebrates such as amphibians, vestibular reflexes are required very early at the onset of locomotor activity. While the formation of inner ears and the assembly of sensory-motor pathways is largely completed soon after hatching, angular and translational/tilt VOR display differential functional onsets and mature with different time courses. Otolith-derived eye movements appear immediately after hatching, whereas the appearance and progressive amelioration of semicircular canal-evoked eye movements is delayed and dependent on the acquisition of sufficiently large semicircular canal diameters...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27875632/variable-phenotypic-expression-and-onset-in-myh14-distal-hmn-phenotype-in-a-large-multigenerational-north-american-family
#12
Stanley Iyadurai, W David Arnold, John T Kissel, Corey Ruhno, Vicki L McGovern, Pamela J Snyder, Thomas W Prior, Jennifer Roggenbuck, Arthur H Burghes, Stephen J Kolb
INTRODUCTION: Distal hereditary motor neuropathy (dHMN) causes distal-predominant weakness without prominent sensory loss. Myosin heavy chain disorders most commonly result in distal myopathy and cardiomyopathy with or without hearing loss, but a complex phenotype with dHMN, myopathy, hoarseness, and hearing loss was reported in a Korean family with a c.2822G>T mutation in MYH14. OBJECTIVE: To report phenotypic features in a North American family with the c.2822G>T in MYH14...
November 22, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/27870427/understanding-the-broad-influence-of-sex-hormones-and-sex-differences-in-the-brain
#13
REVIEW
Bruce S McEwen, Teresa A Milner
Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27865833/defects-in-the-ratio-of-the-dynein-isoform-dhc11-in-the-long-flagella-mutants-of-chlamydomonas-reinhardtii
#14
Marilyn P Sequeira, Sapna Sinha, Mustafa J Motiwalla, Venkatramanan G Rao, Jacinta S D'Souza
The long-flagella mutants (lf1, lf2, lf3 and lf4) of Chlamydomonas reinhardtii are defective in proteins that are required for the assembly of normal flagella, their phenotype being long flagella. In a previous study, we biophysically characterized these mutants for their waveform patterns, swimming speed, beat frequencies and correlated these parameters with their flagellar lengths. We found an anomaly in this correlation and set out to explore the underlying molecular significance, if any. The diverse inner dynein isoforms are the flagellar motors that convert the chemical energy of ATP into the mechanical energy of motility; we probed the presence of one of these isoforms (DHC11, which might help in bend initiation) in the lf mutants and compared it with the wild-type...
November 16, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27864381/lc8-dynein-light-chain-promotes-localization-and-function-of-puf-protein-fbf-2-in-germline-progenitor-cells
#15
Xiaobo Wang, Jenessa R Olson, Dominique Rasoloson, Mary Ellenbecker, Jessica Bailey, Ekaterina Voronina
PUF family translational repressors are conserved developmental regulators, but the molecular function provided by the regions flanking the PUF RNA-binding domain is unknown. In C. elegans, PUF proteins FBF-1 and FBF-2 support germline progenitor maintenance by repressing production of meiotic proteins and use distinct mechanisms to repress their target mRNAs. We identify dynein light chain DLC-1 as an important new regulator of FBF-2 function. DLC-1 directly binds to FBF-2 outside of the RNA-binding domain and promotes FBF-2 localization and function...
November 18, 2016: Development
https://www.readbyqxmd.com/read/27863379/targeted-next-generation-sequencing-identifies-two-novel-mutations-in-sepn1-in-rigid-spine-muscular-dystrophy-1
#16
Yi Dai, Shengran Liang, Yan Huang, Lin Chen, Santasree Banerjee
Rigid spine muscular dystrophy 1 (RSMD1) is a neuromuscular disorder, manifested with poor axial muscle strength, scoliosis and neck weakness, and a variable degree of spinal rigidity with an early ventilatory insufficiency which can lead to death by respiratory failure. Mutations of SEPN1 gene are associated with autosomal recessive RSMD1. Here, we present a clinical molecular study of a Chinese proband with RSMD1. The proband is a 17 years old male, showing difficulty in feeding, delayed motor response, problem in running with frequent fall down, early onset respiratory insufficiency, general muscle weakness and rigid cervical spine...
November 14, 2016: Oncotarget
https://www.readbyqxmd.com/read/27863212/antiangiogenic-therapeutic-potential-of-peptides-derived-from-the-molecular-motor-kif13b-that-transports-vegfr2-to-plasmalemma-in-endothelial-cells
#17
Kaori H Yamada, Hojin Kang, Asrar B Malik
Vascular endothelial growth factor receptor 2 (VEGFR2) localized on the surface of endothelial cells (ECs) is a key determinant of the magnitude and duration of angiogenesis induced by vascular endothelial growth factor (VEGF). The kinesin family plus-end motor KIF13B transports VEGFR2 to the EC surface, and as such, specific inhibition of polarized VEGFR2 trafficking prevents angiogenesis. We designed a series of bioactive peptides based on deep analysis of VEGFR2-binding domain of KIF13B that compete specifically with VEGFR2 binding of KIF13B and thereby potently inhibit angiogenesis...
November 15, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27862327/an-order-in-lewy-body-disorders-retrograde-degeneration-in-hyperbranching-axons-as-a-fundamental-structural-template-accounting-for-focal-multifocal-lewy-body-disease
#18
REVIEW
Toshiki Uchihara 内原 俊記
Initial clinical recognition of "paralysis agitans" by James Parkinson was expanded by Jean-Martin Charcot, who recognized additional clinical findings of his own, such as slowness (distinct from paralysis), rigidity (distinct from spasticity) and characteristic countenance. Charcot assembled these findings under the umbrella of "Parkinson disease (PD)". This purely clinical concept was so prescient and penetrating that subsequent neuropathological and biochemical evidences were ordered along this axis to establish the nigra-central trinity of PD (dopamine depletion, nigral lesion with Lewy bodies: LBs)...
November 14, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27861377/familial-atypical-parkinsonism-with-rare-variant-in-vps35-and-fbxo7-genes-a-case-report
#19
Tereza Bartonikova, Katerina Mensikova, Lenka Mikulicova, Radek Vodicka, Radek Vrtel, Marek Godava, Miroslav Vastik, Michaela Kaiserova, Pavel Otruba, Iva Dolinova, Martin Nevrly, Petr Kanovsky
BACKGROUND: A higher prevalence of parkinsonism was recently identified in southeastern Moravia (Czech Republic). Further research confirmed 3 large pedigrees with familial autosomal-dominant parkinsonism spanning 5 generations. METHODS: This case report concerns a patient belonging to one of these 3 pedigrees, in whom motor and oculomotor symptoms were accompanied by frontal-type dementia, who finally developed a clinical phenotype of progressive supranuclear palsy...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27858289/dynein-light-chain-dynll1-subunit-facilitates-porcine-circovirus-type-2-intracellular-transports-along-microtubules
#20
Sirin Theerawatanasirikul, Nantawan Phecharat, Chaiwat Prawettongsopon, Wanpen Chaicumpa, Porntippa Lekcharoensuk
Microtubule (MT) and dynein motor proteins facilitate intracytoplasmic transport of cellular proteins. Various viruses utilize microtubules and dynein for their movement from the cell periphery to the nucleus. The aim of this study was to investigate the intracellular transport of porcine circovirus type 2 (PCV2) via 8 kDa dynein light chain (DYNLL1, LC8) subunit along the MTs. At 20 μM, vinblastine sulfate inhibited tubulin polymerization resulting in disorganized morphology. In PCV2-infected PK-15 cells, double immunofluorescent labeling showed that the viral particles appeared at the cell periphery and gradually moved to the microtubule organization center (MTOC) at 0-12 hour post inoculation (hpi) while at 20-24 hpi they accumulated in the nucleus...
November 17, 2016: Archives of Virology
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