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https://www.readbyqxmd.com/read/28537258/exploiting-the-kinesin-1-molecular-motor-to-generate-a-virus-membrane-penetration-site
#1
Madhu Sudhan Ravindran, Martin F Engelke, Kristen J Verhey, Billy Tsai
Viruses exploit cellular machineries to penetrate a host membrane and cause infection, a process that remains enigmatic for non-enveloped viruses. Here we probe how the non-enveloped polyomavirus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a crucial infection step. We find that the microtubule-based motor kinesin-1 is recruited to the ER membrane by binding to the transmembrane J-protein B14. Strikingly, this motor facilitates SV40 ER-to-cytosol transport by constructing a penetration site on the ER membrane called a 'focus'...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28536821/impaired-motor-coordination-and-learning-in-mice-lacking-anoctamin-2-calcium-gated-chloride-channels
#2
Franziska Neureither, Katharina Ziegler, Claudia Pitzer, Stephan Frings, Frank Möhrlen
Neurons communicate through excitatory and inhibitory synapses. Both lines of communication are adjustable and allow the fine tuning of signal exchange required for learning processes in neural networks. Several distinct modes of plasticity modulate glutamatergic and GABAergic synapses in Purkinje cells of the cerebellar cortex to promote motor control and learning. In the present paper, we present evidence for a role of short-term ionic plasticity in the cerebellar circuit activity. This type of plasticity results from altered chloride driving forces at the synapses that molecular layer interneurons form on Purkinje cell dendrites...
May 23, 2017: Cerebellum
https://www.readbyqxmd.com/read/28535734/investigational-drugs-in-phase-i-and-phase-ii-for-levodopa-induced-dyskinesia
#3
Silvia Cerri, Francesca Siani, Fabio Blandini
prolonged treatment of Parkinson's disease with L-DOPA results in motor complications, including motor fluctuations and involuntary movements known as L-DOPA induced dyskinesias (LIDs). LIDs represent an additional cause of disability for PD patients and a major challenge for the clinical neurologist. Pre-clinical research has provided invaluable insights into the molecular and neural substrates of LIDs, identifying a number of potential targets for new anti-dyskinetic strategies. Areas covered: this review article is centered on drugs currently in Phase I and II clinical trials for LIDs and their relative pharmacological targets, which include glutamate, acetylcholine, serotonin, adrenergic receptors and additional targets of potential therapeutic interest...
May 24, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28534180/the-c-terminal-kinesin-motor-kifc1-may-participate-in-nuclear-reshaping-and-flagellum-formation-during-spermiogenesis-of-larimichthys-crocea
#4
Dan-Dan Zhang, Xin-Ming Gao, Yong-Qiang Zhao, Cong-Cong Hou, Jun-Quan Zhu
Spermatogenesis is a highly ordered process in the differentiation of male germ cells. Nuclear morphogenesis is one of the most fundamental cellular transformations to take place during spermatogenesis. These striking transformations from spermatogonia to spermatozoa are a result of phase-specific adaption of the cytoskeleton and its association with molecular motor proteins. KIFC1 is a C-terminal kinesin motor protein that plays an essential role in acrosome formation and nuclear reshaping during spermiogenesis in mammals...
May 23, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533764/serum-creatinine-distinguishes-duchenne-muscular-dystrophy-from-becker-muscular-dystrophy-in-patients-aged-%C3%A2-3-years-a-retrospective-study
#5
Liang Wang, Menglong Chen, Ruojie He, Yiming Sun, Juan Yang, Lulu Xiao, Jiqing Cao, Huili Zhang, Cheng Zhang
Here, we investigated correlations between serum creatinine (SCRN) levels and clinical phenotypes of dystrophinopathy in young patients. Sixty-eight patients with dystrophinopathy at the Neuromuscular Clinic, The First Affiliated Hospital, Sun Yat-sen University, were selected for this study. The diagnosis of dystrophinopathy was based on clinical manifestation, biochemical changes, and molecular analysis. Some patients underwent muscle biopsies; SCRN levels were tested when patients were ≤3 years old, and reading frame changes were analyzed...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28533743/neonatal-hypoxia-ischaemia-mechanisms-models-and-therapeutic-challenges
#6
REVIEW
Lancelot J Millar, Lei Shi, Anna Hoerder-Suabedissen, Zoltán Molnár
Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28533393/angular-measurements-of-the-dynein-ring-reveal-a-stepping-mechanism-dependent-on-a-flexible-stalk
#7
Lisa G Lippert, Tali Dadosh, Jodi A Hadden, Vishakha Karnawat, Benjamin T Diroll, Christopher B Murray, Erika L F Holzbaur, Klaus Schulten, Samara L Reck-Peterson, Yale E Goldman
The force-generating mechanism of dynein differs from the force-generating mechanisms of other cytoskeletal motors. To examine the structural dynamics of dynein's stepping mechanism in real time, we used polarized total internal reflection fluorescence microscopy with nanometer accuracy localization to track the orientation and position of single motors. By measuring the polarized emission of individual quantum nanorods coupled to the dynein ring, we determined the angular position of the ring and found that it rotates relative to the microtubule (MT) while walking...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28532681/resveratrol-protects-neuronal-like-cells-expressing-mutant-huntingtin-from-dopamine-toxicity-by-rescuing-atg4-mediated-autophagosome-formation
#8
Chiara Vidoni, Eleonora Secomandi, Andrea Castiglioni, Mariarosa A B Melone, Ciro Isidoro
Parkinsonian-like motor deficits in Huntington's Disease (HD) patients are associated with abnormal dopamine neurotransmission in the striatum. Dopamine metabolism leads to the formation of oxidized dopamine quinones that exacerbates mitochondrial dysfunction with production of reactive oxygen species (ROS) that eventually lead to neuronal cell death. We have previously shown that dopamine-induced oxidative stress triggers apoptotic cell death in dopaminergic neuroblastoma SH-SY5Y cells hyper-expressing the mutant polyQ Huntingtin (polyQ-Htt) protein...
May 19, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28530245/shifting-the-optimal-stiffness-for-cell-migration
#9
Benjamin L Bangasser, Ghaidan A Shamsan, Clarence E Chan, Kwaku N Opoku, Erkan Tüzel, Benjamin W Schlichtmann, Jesse A Kasim, Benjamin J Fuller, Brannon R McCullough, Steven S Rosenfeld, David J Odde
Cell migration, which is central to many biological processes including wound healing and cancer progression, is sensitive to environmental stiffness, and many cell types exhibit a stiffness optimum, at which migration is maximal. Here we present a cell migration simulator that predicts a stiffness optimum that can be shifted by altering the number of active molecular motors and clutches. This prediction is verified experimentally by comparing cell traction and F-actin retrograde flow for two cell types with differing amounts of active motors and clutches: embryonic chick forebrain neurons (ECFNs; optimum ∼1 kPa) and U251 glioma cells (optimum ∼100 kPa)...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529068/adverse-outcome-pathways-application-to-enhance-mechanistic-understanding-of-neurotoxicity
#10
REVIEW
Anna Bal-Price, M E Meek
Recent developments have prompted the transition of empirically based testing of late stage toxicity in animals for a range of different endpoints including neurotoxicity to more efficient and predictive mechanistically based approaches with greater emphasis on measurable key events early in the progression of disease. The adverse outcome pathway (AOP) has been proposed as a simplified organizational construct to contribute to this transition by linking molecular initiating events and earlier (more predictive) key events at lower levels of biological organization to disease outcomes...
May 18, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28528628/millisecond-time-resolution-correlative-light-and-electron-microscopy-for-dynamic-cellular-processes
#11
Ludek Stepanek, Gaia Pigino
Molecular motors propel cellular components at velocities up to microns per second with nanometer precision. Imaging techniques combining high temporal and spatial resolution are therefore indispensable to understand the cellular mechanics at the molecular level. For example, intraflagellar transport (IFT) trains constantly shuttle ciliary components between the base and tip of the eukaryotic cilium. 3-D electron microscopy has revealed IFT train morphology and position, but was unable to correlate these features with the direction of train movement...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28527690/testing-cognitive-functions-in-rodent-disease-models-present-pitfalls-and-future-perspectives
#12
REVIEW
Heikki Tanila
Testing of cognitive functions in rodent disease models constitutes a substantial sector of behavioral neuroscience. It is most often needed in phenotyping genetically modified new rodent (usually mouse) lines or in preclinical testing of cognitive effects of new CNS drugs. This review concerns present pitfalls and future perspectives in this large field, with an emphasis on memory testing in CNS disease models and their preclinical drug testing. It is important to realize that no behavioral test is specific for a single cognitive domain...
May 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28525545/gene-co-expression-network-analysis-for-identifying-modules-and-functionally-enriched-pathways-in-sca2
#13
Lance T Pflieger, Warunee Dansithong, Sharan Paul, Daniel Scoles, Karla P Figueroa, Pratap Meera, Thomas S Otis, Julio C Facelli, Stefan M Pulst
Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease caused by CAG repeat expansion in the ATXN2 gene. The repeat resides in an encoded region of the gene resulting in polyglutamine (polyQ) expansion which has been assumed to result in gain of function, predominantly, for the ATXN2 protein. We evaluated temporal cerebellar expression profiles by RNA sequencing of ATXN2Q127 mice vs wildtype littermates. ATXN2Q127 mice are characterized by a progressive motor phenotype onset, and have progressive cerebellar molecular and neurophysiological (Purkinje cell firing frequency) phenotypes...
May 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28524188/in-situ-control-of-polymer-helicity-with-a-non-covalently-bound-photoresponsive-molecular-motor-dopant
#14
Thomas van Leeuwen, G Henrieke Heideman, Depeng Zhao, Sander J Wezenberg, Ben L Feringa
The transfer of chirality from a molecular motor to a dynamic helical polymer via ionic interactions was investigated. A dopant with photoswitchable chirality was able to induce a preferred helicity in a poly(phenylacetylene) polymer and the helicity is inverted upon irradiation. The findings described herein will advance the development of functional and responsive polymeric systems.
May 19, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28522961/energy-homeostasis-and-abnormal-rna-metabolism-in-amyotrophic-lateral-sclerosis
#15
REVIEW
Yu-Ju Liu, Po-Yi Tsai, Yijuang Chern
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28515487/functional-interaction-between-fus-and-smn-underlies-sma-like-splicing-changes-in-wild-type-hfus-mice
#16
Alessia Mirra, Simona Rossi, Silvia Scaricamazza, Michela Di Salvio, Illari Salvatori, Cristiana Valle, Paola Rusmini, Angelo Poletti, Gianluca Cestra, Maria Teresa Carrì, Maur O Cozzolino
Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS) point to dysfunction in RNA processing as a major pathogenic mechanism. However, whether a precise RNA pathway is particularly affected remains unknown. Evidence suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e. regulation of alternative splicing, and that disturbances in SMN-regulated functions, either caused by depletion of SMN protein (as in the case of SMA) or by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a common theme in both diseases...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514764/trim32-affects-the-recovery-of-motor-function-following-spinal-cord-injury-through-regulating-proliferation-of-glia
#17
Qiang Fu, Ming-Ming Zou, Jian-Wei Zhu, Yan Zhang, Wen-Jin Chen, Mei Cheng, Chun-Feng Liu, Quan-Hong Ma, Ru-Xiang Xu
Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after spinal cord injury (SCI). However, the underlying molecular mechanisms remain unclear. In the present study, we identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following SCI. We further observe that deficiency of TRIM32 results in increased numbers of astrocytes and microglia, which is accompanied by enhanced proliferation of both cells and increased secretion of interleukin (IL)-1 and IL-10...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513584/kinesin-5-independent-mitotic-spindle-assembly-requires-the-antiparallel-microtubule-crosslinker-ase1-in-fission-yeast
#18
Sergio A Rincon, Adam Lamson, Robert Blackwell, Viktoriya Syrovatkina, Vincent Fraisier, Anne Paoletti, Meredith D Betterton, Phong T Tran
Bipolar spindle assembly requires a balance of forces where kinesin-5 produces outward pushing forces to antagonize the inward pulling forces from kinesin-14 or dynein. Accordingly, Kinesin-5 inactivation results in force imbalance leading to monopolar spindle and chromosome segregation failure. In fission yeast, force balance is restored when both kinesin-5 Cut7 and kinesin-14 Pkl1 are deleted, restoring spindle bipolarity. Here we show that the cut7Δpkl1Δ spindle is fully competent for chromosome segregation independently of motor activity, except for kinesin-6 Klp9, which is required for anaphase spindle elongation...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28512223/kinematics-of-the-lever-arm-swing-in-myosin-vi
#19
Mauro L Mugnai, D Thirumalai
Myosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively toward the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a unique coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps. First, the motor domain attains the poststroke conformation without directing the lever arm forward; and second, the lever arm reaches the poststroke orientation by undergoing a rotational diffusion...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28511918/molecular-imaging-of-serotonin-degeneration-in-mild-cognitive-impairment
#20
Gwenn S Smith, Frederick S Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J Sodums, Christopher M Marano, Cynthia A Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean F Wong, Clifford I Workman
Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions, as well as the cell bodies of origin (raphe nuclei)...
May 13, 2017: Neurobiology of Disease
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