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https://www.readbyqxmd.com/read/28447571/neuroprotective-effects-of-betulin-in-pharmacological-and-transgenic-c-elegans-models-of-parkinson-s-disease
#1
Chia-Wen Tsai, Rong-Tzong Tsai, Shih-Ping Liu, Chang-Shi Chen, Min-Chen Tsai, Shao-Hsuan Chien, Huey-Shan Hung, Shinn-Zong Lin, Woei-Cherng Shyu, Ru-Huei Fu
Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly.It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Currently, therapeutics for PD provide satisfactory symptom relief, but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#2
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28445732/the-hect-family-ubiquitin-ligase-eel-1-regulates-neuronal-function-and-development
#3
Karla J Opperman, Ben Mulcahy, Andrew C Giles, Monica G Risley, Rayna L Birnbaum, Erik D Tulgren, Ken Dawson-Scully, Mei Zhen, Brock Grill
Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with intellectual disability, but it remains unknown whether HUWE1 functions in post-mitotic neurons to affect circuit function. Using genetics, pharmacology, and electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans, preferentially regulates GABAergic presynaptic transmission. Decreasing or increasing EEL-1 function alters GABAergic transmission and the excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to impaired locomotion and increased sensitivity to electroshock...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445613/neuronal-distribution-of-tyramine-and-the-tyramine-receptor-amtar1-in-the-honeybee-brain
#4
Markus Thamm, Christina Scholl, Tina Reim, Kornelia Grübel, Karin Möller, Wolfgang Rössler, Ricarda Scheiner
Tyramine is an important neurotransmitter, neuromodulator, and neurohormone in insects. In honeybees, it is assumed to have functions in modulating sensory responsiveness and controlling motor behavior. Tyramine can bind to two characterized receptors in honeybees, both of which are coupled to intracellular cAMP pathways. How tyramine acts on neuronal, cellular and circuit levels is unclear. We investigated the spatial brain expression of the tyramine receptor AmTAR1 using a specific antibody. This antibody detects a membrane protein of the expected molecular weight in Western blot analysis...
April 26, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28444617/computational-theory-underlying-acute-vestibulo-ocular-reflex-motor-learning-with-cerebellar-long-term-depression-and-long-term-potentiation
#5
Keiichiro Inagaki, Yutaka Hirata
The vestibulo-ocular reflex (VOR) can be viewed as an adaptive control system that maintains compensatory eye movements during head motion. As the cerebellar flocculus is intimately involved in this adaptive motor control of the VOR, the VOR has been a popular model system for investigating cerebellar motor learning. Long-term depression (LTD) and long-term potentiation (LTP) at the parallel fiber-Purkinje cell synapses are considered to play major roles in cerebellar motor learning. A recent study using mutant mice demonstrated cerebellar motor learning with hampered LTD; the study concluded that the parallel fiber-Purkinje cell LTD is not essential...
April 25, 2017: Cerebellum
https://www.readbyqxmd.com/read/28443644/a-reciprocal-regulatory-loop-between-taz-yap-and-g-protein-g%C3%AE-s-regulates-schwann-cell-proliferation-and-myelination
#6
Yaqi Deng, Lai Man Natalie Wu, Shujun Bai, Chuntao Zhao, Haibo Wang, Jincheng Wang, Lingli Xu, Masahide Sakabe, Wenhao Zhou, Mei Xin, Q Richard Lu
Schwann cell (SC) myelination in the peripheral nervous system is essential for motor function, and uncontrolled SC proliferation occurs in cancer. Here, we show that a dual role for Hippo effectors TAZ and YAP in SC proliferation and myelination through modulating G-protein expression and interacting with SOX10, respectively. Developmentally regulated mutagenesis indicates that TAZ/YAP are critical for SC proliferation and differentiation in a stage-dependent manner. Genome-wide occupancy mapping and transcriptome profiling reveal that nuclear TAZ/YAP promote SC proliferation by activating cell cycle regulators, while targeting critical differentiation regulators in cooperation with SOX10 for myelination...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28442770/design-principles-governing-chemomechanical-coupling-of-kinesin
#7
Tomonari Sumi
A systematic chemomechanical network model for the molecular motor kinesin is presented in this report. The network model is based on the nucleotide-dependent binding affinity of the heads to an microtubule (MT) and the asymmetries and similarities between the chemical transitions caused by the intramolecular strain between the front and rear heads. The network model allows for multiple chemomechanical cycles and takes into account all possible mechanical transitions between states in which one head is strongly bound and the other head is weakly bound to an MT...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442535/multiple-kinesin-14-family-members-drive-microtubule-minus-end-directed-transport-in-plant-cells
#8
Moé Yamada, Yohko Tanaka-Takiguchi, Masahito Hayashi, Momoko Nishina, Gohta Goshima
Minus end-directed cargo transport along microtubules (MTs) is exclusively driven by the molecular motor dynein in a wide variety of cell types. Interestingly, during evolution, plants have lost the genes encoding dynein; the MT motors that compensate for dynein function are unknown. Here, we show that two members of the kinesin-14 family drive minus end-directed transport in plants. Gene knockout analyses of the moss Physcomitrella patens revealed that the plant-specific class VI kinesin-14, KCBP, is required for minus end-directed transport of the nucleus and chloroplasts...
April 25, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28438991/differentiation-of-v2a-interneurons-from-human-pluripotent-stem-cells
#9
Jessica C Butts, Dylan A McCreedy, Jorge Alexis Martinez-Vargas, Frederico N Mendoza-Camacho, Tracy A Hookway, Casey A Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C McDevitt
The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10(+) V2a interneurons from human pluripotent stem cells (hPSCs)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28437027/reprogrammable-assembly-of-molecular-motor-on-solid-surfaces-via-dynamic-bonds
#10
Li Yu, Jian Sun, Qian Wang, Yan Guan, Le Zhou, Jingxuan Zhang, Lanying Zhang, Huai Yang
Controllable assembly of molecular motors on solid surfaces is a fundamental issue for providing them to perform physical tasks. However, it can hardly be achieved by most previous methods due to their inherent limitations. Here, a general strategy is designed for the reprogrammable assembly of molecular motors on solid surfaces based on dynamic bonds. In this method, molecular motors with disulfide bonds can be remotely, reversibly, and precisely attached to solid surfaces with disulfide bonds, regardless of their chemical composition and microstructure...
April 24, 2017: Small
https://www.readbyqxmd.com/read/28433265/high-pressure-microscopy-for-tracking-dynamic-properties-of-molecular-machines
#11
Masayoshi Nishiyama
High-pressure microscopy is one of the powerful techniques to visualize the effects of hydrostatic pressures on research targets. It could be used for monitoring the pressure-induced changes in the structure and function of molecular machines in vitro and in vivo. This review focuses on the dynamic properties of the assemblies and machines, analyzed by means of high-pressure microscopy measurement. We developed a high-pressure microscope that is optimized both for the best image formation and for the stability to hydrostatic pressure up to 150 MPa...
March 30, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28430595/minus-end-directed-kinesin-14-kifc1-regulates-the-positioning-and-architecture-of-the-golgi-apparatus
#12
Zhen-Yu She, Meng-Ying Pan, Fu-Qing Tan, Wan-Xi Yang
The Golgi apparatus is the central organelle along the eukaryotic secretory and endocytic pathway. In non-polarized mammalian cells, the Golgi complex is usually located proximal to the nucleus at the cell center and is closely associated with the microtubule organizing center. Microtubule networks are essential in the organization and central localization of the Golgi apparatus, but the molecular basis underlying these processes are poorly understood. Here we reveal that minus end-directed kinesin-14 KIFC1 proteins are required for the structural integrity and positioning of the Golgi complex in non-polarized mammalian cells...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430193/self-propelled-supramolecular-nanomotors-with-temperature-responsive-speed-regulation
#13
Yingfeng Tu, Fei Peng, Xiaofeng Sui, Yongjun Men, Paul B White, Jan C M van Hest, Daniela A Wilson
Self-propelled catalytic micro- and nanomotors have been the subject of intense study over the past few years, but it remains a continuing challenge to build in an effective speed-regulation mechanism. Movement of these motors is generally fully dependent on the concentration of accessible fuel, with propulsive movement only ceasing when the fuel consumption is complete. Here we report a demonstration of control over the movement of self-assembled stomatocyte nanomotors via a molecularly built, stimulus-responsive regulatory mechanism...
May 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28430047/arf-gaps-and-molecular-motors
#14
Ruibai Luo, Christine E Reed, Jeffrey A Sload, Linda Wordeman, Paul A Randazzo, Pei-Wen Chen
Arf GTPase-activating proteins (Arf GAPs) were first identified as regulators of the small GTP-binding proteins ADP-ribosylation factors (Arfs). The Arf GAPs are a large family of proteins in metazoans, outnumbering the Arfs that they regulate. The members of the Arf GAP family have complex domain structures and some have been implicated in particular cellular functions, such as cell migration, or with particular pathologies, such as tumor invasion and metastasis. The specific effects of Arfs sometimes depend on the Arf GAP involved in their regulation...
April 21, 2017: Small GTPases
https://www.readbyqxmd.com/read/28428759/morphological-regeneration-and-functional-recovery-of-neuromuscular-junctions-after-tourniquet-induced-injuries-in-mouse-hindlimb
#15
Huiyin Tu, Dongze Zhang, Ryan M Corrick, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Tourniquet application and its subsequent release cause serious injuries to the skeletal muscle, nerve, and neuromuscular junction (NMJ) due to mechanical compression and ischemia-reperfusion (IR). Monitoring structural and functional repair of the NMJ, nerve, and skeletal muscle after tourniquet-induced injuries is beneficial in exploring potential cellular and molecular mechanisms responsible for tourniquet-induced injuries, and for establishing effective therapeutic interventions. Here, we observed long-term morphological and functional changes of the NMJ in a murine model of tourniquet-induced hindlimb injuries...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28427933/high-molecular-weight-genomic-dna-mini-prep-for-filamentous-fungi
#16
Mi-Kyung Lee, Hee-Soo Park, Kap-Hoon Han, Seung-Beom Hong, Jae-Hyuk Yu
Purification of high quality genomic DNA (gDNA) from filamentous fungi suitable for whole genome sequencing has previously involved many steps. Here, we report a simple and easy-to-follow mini-preparation protocol for high molecular weight (∼20kb) gDNA from filamentous fungi including Aspergillus and Eurotium. This comprehensive protocol includes graphic step-by-step instructions for inoculation, homogenization, and purification of gDNA. The most critical step is a thorough 3-5min homogenization of the freeze-dried mycelium using a motorized hand-held homogenizer with a mini spatula inserted...
April 18, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28427899/energy-and-information-flows-in-biological-systems-bioenergy-transduction-of-v1-atpase-rotary-motor-and-dynamics-of-thermodynamic-entropy-in-information-flows
#17
REVIEW
Ichiro Yamato, Takeshi Murata, Andrei Khrennikov
We classify research fields in biology with respect to flows of materials, energy, and information. We investigate energy transducing mechanisms in biology, using as a representative the typical molecular rotary motor V1-ATPase from a bacterium Enterococcus hirae. The structures of several intermediates of the rotary motor are described and the molecular mechanism of the motor converting chemical energy into mechanical energy is discussed. Comments and considerations on the information flows in biology, especially on the thermodynamic entropy in quantum physical and biological systems, are presented in section 3 in a biologist friendly manner...
April 17, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28426968/map2-defines-a-pre-axonal-filtering-zone-to-regulate-kif1-versus-kif5-dependent-cargo-transport-in-sensory-neurons
#18
Laura F Gumy, Eugene A Katrukha, Ilya Grigoriev, Dick Jaarsma, Lukas C Kapitein, Anna Akhmanova, Casper C Hoogenraad
Polarized cargo transport is essential for neuronal function. However, the minimal basic components required for selective cargo sorting and distribution in neurons remain elusive. We found that in sensory neurons the axon initial segment is largely absent and that microtubule-associated protein 2 (MAP2) defines the cargo-filtering zone in the proximal axon. Here, MAP2 directs axonal cargo entry by coordinating the activities of molecular motors. We show that distinct kinesins differentially regulate cargo velocity: kinesin-3 drives fast axonal cargo trafficking, while kinesin-1 slows down axonal cargo transport...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28426667/bioenergetic-status-modulates-motor-neuron-vulnerability-and-pathogenesis-in-a-zebrafish-model-of-spinal-muscular-atrophy
#19
Penelope J Boyd, Wen-Yo Tu, Hannah K Shorrock, Ewout J N Groen, Roderick N Carter, Rachael A Powis, Sophie R Thomson, Derek Thomson, Laura C Graham, Anna A L Motyl, Thomas M Wishart, J Robin Highley, Nicholas M Morton, Thomas Becker, Catherina G Becker, Paul R Heath, Thomas H Gillingwater
Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles...
April 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28426052/artificial-molecular-motors
#20
REVIEW
Salma Kassem, Thomas van Leeuwen, Anouk S Lubbe, Miriam R Wilson, Ben L Feringa, David A Leigh
Motor proteins are nature's solution for directing movement at the molecular level. The field of artificial molecular motors takes inspiration from these tiny but powerful machines. Although directional motion on the nanoscale performed by synthetic molecular machines is a relatively new development, significant advances have been made. In this review an overview is given of the principal designs of artificial molecular motors and their modes of operation. Although synthetic molecular motors have also found widespread application as (multistate) switches, we focus on the control of directional movement, both at the molecular scale and at larger magnitudes...
April 20, 2017: Chemical Society Reviews
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