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https://www.readbyqxmd.com/read/29167533/muscle-mri-and-functional-outcome-measures-in-becker-muscular-dystrophy
#1
Andrea Barp, Luca Bello, Luca Caumo, Paola Campadello, Claudio Semplicini, Annalisa Lazzarotto, Gianni Sorarù, Chiara Calore, Alessandro Rampado, Raffaella Motta, Roberto Stramare, Elena Pegoraro
Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167371/spontaneous-oscillations-of-elastic-filaments-induced-by-molecular-motors
#2
Gabriele De Canio, Eric Lauga, Raymond E Goldstein
It is known from the wave-like motion of microtubules in motility assays that the piconewton forces that motors produce can be sufficient to bend the filaments. In cellular phenomena such as cytosplasmic streaming, molecular motors translocate along cytoskeletal filaments, carrying cargo which entrains fluid. When large numbers of such forced filaments interact through the surrounding fluid, as in particular stages of oocyte development in Drosophila melanogaster, complex dynamics are observed, but the detailed mechanics underlying them has remained unclear...
November 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29163139/exercise-induced-neuroprotection-of-the-nigrostriatal-dopamine-system-in-parkinson-s-disease
#3
REVIEW
Lijuan Hou, Wei Chen, Xiaoli Liu, Decai Qiao, Fu-Ming Zhou
Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29163054/motor-deficits-and-cerebellar-atrophy-in-elovl5-knock-out-mice
#4
Eriola Hoxha, Rebecca M C Gabriele, Ilaria Balbo, Francesco Ravera, Linda Masante, Vanessa Zambelli, Cristian Albergo, Nico Mitro, Donatella Caruso, Eleonora Di Gregorio, Alfredo Brusco, Barbara Borroni, Filippo Tempia
Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5. The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the main symptoms of patients, motor deficits at the beam balance test and hyposmia. The cerebellar cortex of Elovl5 knock out mice showed a reduction of thickness of the molecular layer, already detectable at 6 months of age, confirmed at 12 and 18 months...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29163029/micrornas-and-target-genes-as-biomarkers-for-the-diagnosis-of-early-onset-of-parkinson-disease
#5
REVIEW
Ahmad R Arshad, Siti A Sulaiman, Amalia A Saperi, Rahman Jamal, Norlinah Mohamed Ibrahim, Nor Azian Abdul Murad
Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162650/evidence-that-a-steric-clash-in-the-upper-50kda-domain-of-the-motor-myo2p-leads-to-cytokinesis-defects-in-fission-yeast
#6
Saravanan Palani, Ramanujam Srinivasan, Paola Zambon, Anton Kamnev, Pananghat Gayathri, Mohan K Balasubramanian
Cytokinesis in many eukaryotes requires a contractile actomyosin ring that is placed at the division site. In fission yeast, an attractive organism for the study of cytokinesis, actomyosin ring assembly and contraction requires the myosin II heavy chain, Myo2p. Although myo2-E1, a temperature-sensitive mutant defective in the upper 50KDa domain of Myo2p has been studied extensively, the molecular basis of cytokinesis defect is not understood. Here we isolate myo2-E1-Sup2, an intragenic suppressor that contains the original mutation in myo2-E1 (G345R) and a second mutation in the upper 50KDa domain (Y297C)...
November 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29162634/update-on-myosin-motors-molecular-mechanisms-and-physiological-functions
#7
Jennifer M Ryan, Andreas Nebenfuehr
No abstract text is available yet for this article.
November 21, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29162464/biochemical-and-biophysical-characterization-of-curcumin-binding-to-human-mitotic-kinesin-eg5-iinsights-into-the-inhibitory-mechanism-of-curcumin-on-eg5
#8
Darpan Raghav, Jomon Sebastian, Krishnan Rathinasamy
In this study we have characterized the biochemical and biophysical interactions of curcumin with the mitotic kinesin Eg5 which plays a pivotal role in the separation of centrosomes during cell division. Curcumin bound to the purified Eg5 (Eg5-437H) with a Kd value of 7.8mM. The temperature dependent binding analysis and evaluation of thermodynamic parameters indicated the involvement of static quenching mechanism in the binding process. Evidences from competition experiment with monastrol indicated that curcumin bound to Eg5 at a novel druggable site...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29159890/whole-exome-sequencing-reveals-a-mutation-in-armc9-as-a-cause-of-mental-retardation-ptosis-and-polydactyly
#9
Anjana Kar, Shubha R Phadke, Aneek Das Bhowmik, Ashwin Dalal
Intellectual disability (ID) refers to deficits in mental abilities, social behavior, and motor skills to perform activities of daily living as compared to peers. Numerous genetic and environmental factors may be responsible for ID. We report on elucidation of molecular basis for syndromic ID associated with ptosis, polydactyly, and MRI features suggestive of Joubert syndrome using homozygosity mapping followed by exome sequencing. The analysis revealed a novel synonymous variation p.T293T (c.879G>A) which leads to a splicing defect in ARMC9 gene...
November 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29159770/jip3-localises-to-exocytic-vesicles-and-focal-adhesions-in-the-growth-cones-of-differentiated-pc12-cells
#10
Patrick T Caswell, Martin Dickens
The JNK-interacting protein 3 (JIP3) is a molecular scaffold, expressed predominantly in neurons, that serves to coordinate the activation of the c-Jun N-terminal kinase (JNK) by binding to JNK and the upstream kinases involved in its activation. The JNK pathway is involved in the regulation of many cellular processes including the control of cell survival, cell death and differentiation. JIP3 also associates with microtubule motor proteins such as kinesin and dynein and is likely an adapter protein involved in the tethering of vesicular cargoes to the motors involved in axonal transport in neurons...
November 20, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29158401/kinesin-dependent-mechanism-for-controlling-triglyceride-secretion-from-the-liver
#11
Priyanka Rai, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S Kamat, Roop Mallik
Despite massive fluctuations in its internal triglyceride content, the liver secretes triglyceride under tight homeostatic control. This buffering function is most visible after fasting, when liver triglyceride increases manyfold but circulating serum triglyceride barely fluctuates. How the liver controls triglyceride secretion is unknown, but is fundamentally important for lipid and energy homeostasis in animals. Here we find an unexpected cellular and molecular mechanism behind such control. We show that kinesin motors are recruited to triglyceride-rich lipid droplets (LDs) in the liver by the GTPase ARF1, which is a key activator of lipolysis...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29157304/a-novel-vector-for-transgenesis-in-the-rat-cns
#12
T Peter Lopez, Kurt Giles, Brittany N Dugger, Abby Oehler, Carlo Condello, Zuzana Krejciova, Julian A Castaneda, George A Carlson, Stanley B Prusiner
The larger brain of the rat enables a much greater repertoire of complex behaviors than mice, likely making rats preferential for investigating neurodegeneration. Because molecular tools for specific expression of transgenes in the rat brain are sparse, we chose Prnp encoding the prion protein (PrP) to develop a novel vector to drive transgene expression in the rat brain. We compared the rat Prnp sequence with mouse and Syrian hamster Prnp sequences, identifying conserved genetic elements and hypothesizing that these elements would be able to drive neuronal transgene expression...
November 21, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29156093/functional-and-molecular-outcomes-of-the-human-masticatory-muscles
#13
REVIEW
Gaetano Isola, Giuseppe Anastasi, Giovanni Matarese, Ray C Williams, Giuseppina Cutroneo, Pietro Bracco, Maria Grazia Piancino
The masticatory muscles achieve a broad range of different activities such as chewing, sucking, swallowing and speech. In order to accomplish these duties, masticatory muscles have a unique and heterogeneous structure and fibre composition, enabling them to produce their strength and contraction speed largely dependent on their motor units and myosin proteins that can change in response to genetic and environmental factors. Human masticatory muscles express unique myosin isoforms, including a combination of thick fibers, expressing myosin light chains (MyLC) and myosin class I and II heavy chains (MyHC) -IIA, -IIX, α-cardiac, embryonic and neonatal and thin fibers, respectively...
November 20, 2017: Oral Diseases
https://www.readbyqxmd.com/read/29155762/high-throughput-analysis-of-locomotor-behavior-in-the-drosophila-island-assay
#14
Ilse Eidhof, Michaela Fenckova, Dei M Elurbe, Bart van de Warrenburg, Anna Castells Nobau, Annette Schenck
Advances in next-generation sequencing technologies contribute to the identification of (candidate) disease genes for movement disorders and other neurological diseases at an increasing speed. However, little is known about the molecular mechanisms that underlie these disorders. The genetic, molecular, and behavioral toolbox of Drosophila melanogaster makes this model organism particularly useful to characterize new disease genes and mechanisms in a high-throughput manner. Nevertheless, high-throughput screens require efficient and reliable assays that, ideally, are cost-effective and allow for the automatized quantification of traits relevant to these disorders...
November 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155749/immobilization-of-caenorhabditis-elegans-to-analyze-intracellular-transport-in-neurons
#15
Shinsuke Niwa
Axonal transport and intraflagellar transport (IFT) are essential for axon and cilia morphogenesis and function. Kinesin superfamily proteins and dynein are molecular motors that regulate anterograde and retrograde transport, respectively. These motors use microtubule networks as rails. Caenorhabditis elegans (C. elegans) is a powerful model organism to study axonal transport and IFT in vivo. Here, I describe a protocol to observe axonal transport and IFT in living C. elegans. Transported cargo can be visualized by tagging cargo proteins using fluorescent proteins such as green fluorescent protein (GFP)...
October 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154435/braking-of-a-light-driven-molecular-rotary-motor-by-chemical-stimuli
#16
Thomas van Leeuwen, Wojciech Danowski, Stefano F Pizzolato, Peter Štacko, Sander J Wezenberg, Ben L Feringa
Artificial molecular motors hold great promise for application in responsive functional materials as well as to control the properties of biohybrid systems. Herein a strategy is reported to modulate the rotation of light-driven molecular motors. That is, the rotary speed of a molecular motor, functionalized with a biphenol moiety, could be decreased in situ by non-covalent substrate binding, as was established by (1) H NMR and UV/Vis spectroscopy. These findings constitute an important step in the development of multi-responsive molecular machinery...
November 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29149772/natural-history-of-infantile-onset-spinal-muscular-atrophy
#17
Stephen J Kolb, Christopher S Coffey, Jon W Yankey, Kristin Krosschell, W David Arnold, Seward B Rutkove, Kathryn J Swoboda, Sandra P Reyna, Ai Sakonju, Basil T Darras, Richard Shell, Nancy Kuntz, Diana Castro, Julie Parsons, Anne M Connolly, Claudia A Chiriboga, Craig McDonald, W Bryan Burnette, Klaus Werner, Mathula Thangarajh, Perry B Shieh, Erika Finanger, Merit E Cudkowicz, Michelle M McGovern, D Elizabeth McNeil, Richard Finkel, Susan T Iannaccone, Edward Kaye, Allison Kingsley, Samantha R Renusch, Vicki L McGovern, Xueqian Wang, Phillip G Zaworski, Thomas W Prior, Arthur H M Burghes, Amy Bartlett, John T Kissel
OBJECTIVE: Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death prior to age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes. METHODS: A longitudinal, multi-center, prospective natural history study enrolled 26 SMA infants, and 27 control infants less than six months of age...
November 17, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29148051/mechanical-parameters-of-the-molecular-motor-myosin-ii-determined-in-permeabilised-fibres-from-slow-and-fast-skeletal-muscles-of-the-rabbit
#18
Valentina Percario, Simona Boncompagni, Feliciano Protasi, Irene Pertici, Francesca Pinzauti, Marco Caremani
The skeletal muscle exhibits large functional differences depending on the myosin heavy chain (MHC) isoform expressed in its molecular motor myosin II. The differences in the mechanical features of force generation by myosin isoforms are investigated in situ by using fast sarcomere-level mechanical methods in permeabilised fibres (sarcomere length 2.4 μm, temperature 12°C, 4% dextran T-500) from the slow (soleus, containing the MHC-1 isoform) and the fast (psoas, containing the MHC-2X isoform) skeletal muscle of the rabbit...
November 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29146598/structural-analyses-unravel-the-molecular-mechanism-of-cyclic-di-gmp-regulation-of-bacterial-chemotaxis-via-a-pilz-adaptor-protein
#19
Xin-Fu Yan, Lingyi Xin, Jackie Tan Yen, Yukai Zeng, Shengyang Jin, Qing Wei Cheang, Rachel Andrea Chea Yuen Fong, Keng-Hwee Chiam, Zhao-Xun Liang, Yong-Gui Gao
The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility and pathogenicity. Cdi-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism in c-di-GMP-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ co-crystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa This co-crystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29146505/muscarinic-receptor-oligomerization
#20
REVIEW
Sara Marsango, Richard J Ward, Elisa Alvarez-Curto, Graeme Milligan
G protein coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing numbers of studies have supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of the GPCR oligomerization remain topics of intense speculation...
November 13, 2017: Neuropharmacology
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