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https://www.readbyqxmd.com/read/28805800/optogenetic-control-of-kinetochore-function
#1
Huaiying Zhang, Chanat Aonbangkhen, Ekaterina V Tarasovetc, Edward R Ballister, David M Chenoweth, Michael A Lampson
Kinetochores act as hubs for multiple activities during cell division, including microtubule interactions and spindle checkpoint signaling. Each kinetochore can act autonomously, and activities change rapidly as proteins are recruited to, or removed from, kinetochores. Understanding this dynamic system requires tools that can manipulate kinetochores on biologically relevant temporal and spatial scales. Optogenetic approaches have the potential to provide temporal and spatial control with molecular specificity...
August 14, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28803871/an-rnai-screen-in-a-novel-model-of-oriented-divisions-identifies-the-actin-capping-protein-z-%C3%AE-as-an-essential-regulator-of-spindle-orientation
#2
Florencia di Pietro, Léo Valon, Yingbo Li, Rosette Goïame, Auguste Genovesio, Xavier Morin
Oriented cell divisions are controlled by a conserved molecular cascade involving Gαi, LGN, and NuMA. We developed a new cellular model of oriented cell divisions combining micropatterning and localized recruitment of Gαi and performed an RNAi screen for regulators acting downstream of Gαi. Remarkably, this screen revealed a unique subset of dynein regulators as being essential for spindle orientation, shedding light on a core regulatory aspect of oriented divisions. We further analyze the involvement of one novel regulator, the actin-capping protein CAPZB...
August 4, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28802936/nonmotor-symptoms-in-experimental-models-of-parkinson-s-disease
#3
Nataliya Titova, Anthony H V Schapira, K Ray Chaudhuri, Mubasher A Qamar, Elena Katunina, Peter Jenner
Nonmotor symptoms of Parkinson's disease (PD) range from neuropsychiatric, cognitive to sleep and sensory disorders and can arise from the disease process as well as from drug treatment. The clinical heterogeneity of nonmotor symptoms of PD is underpinned by a wide range of neuropathological and molecular pathology, affecting almost the entire range of neurotransmitters present in brain and the periphery. Understanding the neurobiology and pathology of nonmotor symptoms is crucial to the effective treatment of PD and currently a key unmet need...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802921/imaging-the-nonmotor-symptoms-in-parkinson-s-disease
#4
Tayyabah Yousaf, Heather Wilson, Marios Politis
Parkinson's disease is acknowledged to be a multisystem syndrome, manifesting as a result of multineuropeptide dysfunction, including dopaminergic, cholinergic, serotonergic, and noradrenergic deficits. This multisystem disorder ultimately leads to the presentation of a range of nonmotor symptoms, now appreciated to be an integral part of the disease-specific spectrum of symptoms, often preceding the diagnosis of motor Parkinson's disease. In this chapter, we review the dopaminergic and nondopaminergic basis of these symptoms by exploring the neuroimaging evidence based on several techniques including positron emission tomography, single-photon emission computed tomography molecular imaging, magnetic resonance imaging, functional magnetic resonance imaging, and diffusion tensor imaging...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28801619/repetitive-motor-cortex-stimulation-reinforces-the-pain-modulation-circuits-of-peripheral-neuropathic-pain
#5
Myeounghoon Cha, Sun Woo Um, Minjee Kwon, Taick Sang Nam, Bae Hwan Lee
Recent evidence indicates that motor cortex stimulation (MCS) is a potentially effective treatment for chronic neuropathic pain. However, the neural mechanisms underlying the attenuated hyperalgesia after MCS are not completely understood. In this study, we investigated the neural mechanism of the effects of MCS using an animal model of neuropathic pain. After 10 daily sessions of MCS, repetitive MCS reduced mechanical allodynia and contributed to neuronal changes in the anterior cingulate cortex (ACC). Interestingly, inhibition of protein kinase M zeta (PKMζ), a regulator of synaptic plasticity, in the ACC blocked the effects of repetitive MCS...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800335/an-overview-of-human-immunodeficiency-virus-type-1-associated-common-neurological-complications-does-aging-pose-a-challenge
#6
Anantha Ram Nookala, Joy Mitra, Nitish S Chaudhari, Muralidhar L Hegde, Anil Kumar
With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications...
August 9, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28799908/the-molecular-basis-of-erythrocyte-invasion-by-malaria-parasites
#7
REVIEW
Alan F Cowman, Christopher J Tonkin, Wai-Hong Tham, Manoj T Duraisingh
Plasmodium species cause malaria by proliferating in human erythrocytes. Invasion of immunologically privileged erythrocytes provides a relatively protective niche as well as access to a rich source of nutrients. Plasmodium spp. target erythrocytes of different ages, but share a common mechanism of invasion. Specific engagement of erythrocyte receptors defines target cell tropism, activating downstream events and resulting in the physical penetration of the erythrocyte, powered by the parasite's actinomyosin-based motor...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28797588/longitudinal-assessments-in-discordant-twins-with-sma
#8
Marika Pane, Leonardo Lapenta, Emanuela Abiusi, Roberto de Sanctis, Marco Luigetti, Concetta Palermo, Domiziana Ranalli, Stefania Fiori, Francesco Danilo Tiziano, Eugenio Mercuri
We report longitudinal clinical and neurophysiological assessments in twins affected by spinal muscular atrophy (SMA) with discordant phenotypes. The boy had the homozygous deletion of SMN1, a typical type 1 SMA course, and died at the age of eight months. His twin sister, asymptomatic at the time of the diagnosis in her brother, had the same genetic defect but she developed clinical and electrophysiological signs of type 2 SMA. The reduction of tendon reflexes was the first clinical sign at the age of 4 months, followed within few weeks, by a mild decrement in the amplitude of the compound motor action potentials...
July 8, 2017: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28793971/unlocking-the-mystery-of-biomarkers-a-brief-introduction-challenges-and-opportunities-in-parkinson-disease
#9
Thomas F Tropea, Alice S Chen-Plotkin
First described 200 years ago, Parkinson Disease (PD) exhibits considerable heterogeneity in clinical presentation, as well as trajectory of motor and non-motor decline. This heterogeneity, in turn, complicates the planning of clinical research, particularly trials of disease-modifying therapies, as well as the care of PD patients. While clinical features have been used to delineate subgroups of PD patients, clinical subtyping is hampered by change in features over time, and clinical subtyping may fail to capture the biological processes underlying heterogeneity...
July 22, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28793211/design-of-elastic-networks-with-evolutionary-optimized-long-range-communication-as-mechanical-models-of-allosteric-proteins
#10
Holger Flechsig
Allosteric effects often underlie the activity of proteins, and elucidating generic design aspects and functional principles unique to allosteric phenomena represent a major challenge. Here an approach consisting of the in silico design of synthetic structures, which, as the principal element of allostery, encode dynamical long-range coupling among two sites, is presented. The structures are represented by elastic networks, similar to coarse-grained models of real proteins. A strategy of evolutionary optimization was implemented to iteratively improve allosteric coupling...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28793209/structural-rearrangement-upon-fragmentation-of-the-stability-core-of-the-als-linked-protein-tdp-43
#11
Brittany R Morgan, Jill A Zitzewitz, Francesca Massi
Amyotrophic lateral sclerosis (ALS) is the most common adult degenerative motor neuron disease. Experimental evidence indicates a direct role of transactive-response DNA-binding protein 43 (TDP-43) in the pathology of ALS and other neurodegenerative diseases. TDP-43 has been identified as a major component of cytoplasmic inclusions in patients with sporadic ALS; however, the molecular basis of the disease mechanism is not yet fully understood. Fragmentation within the second RNA recognition motif (RRM2) of TDP-43 has been observed in patient tissues and may play a role in the formation of aggregates in disease...
August 8, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28791401/implications-of-white-matter-damage-in-amyotrophic-lateral-sclerosis-review
#12
Ting Zhou, Tina Khorshid Ahmad, Kiana Gozda, Jessica Truong, Jiming Kong, Michael Namaka
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal‑glial interactions...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28789884/single-molecule-imaging-and-manipulation-of-biomolecular-machines-and-systems
#13
REVIEW
Ryota Iino, Tatsuya Iida, Akihiko Nakamura, Ei-Ichiro Saita, Huijuan You, Yasushi Sako
Biological molecular machines support various activities and behaviors of cells, such as energy production, signal transduction, growth, differentiation, and migration. Scope of Review We provide an overview of single-molecule imaging methods involving both small and large probes used to monitor the dynamic motions of molecular machines in vitro (purified proteins) and in living cells, and single-molecule manipulation methods used to measure the forces, mechanical properties and responses of biomolecules. We also introduce several examples of single-molecule analysis, focusing primarily on motor proteins and signal transduction systems...
August 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28780783/implications-of-circadian-rhythm-in-dopamine-and-mood-regulation
#14
REVIEW
Jeongah Kim, Sangwon Jang, Han Kyoung Choe, Sooyoung Chung, Gi Hoon Son, Kyungjin Kim
Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm...
July 31, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28775348/mechanistic-and-structural-basis-for-activation-of-cardiac-myosin-force-production-by-omecamtiv-mecarbil
#15
Vicente J Planelles-Herrero, James J Hartman, Julien Robert-Paganin, Fady I Malik, Anne Houdusse
Omecamtiv mecarbil is a selective, small-molecule activator of cardiac myosin that is being developed as a potential treatment for heart failure with reduced ejection fraction. Here we determine the crystal structure of cardiac myosin in the pre-powerstroke state, the most relevant state suggested by kinetic studies, both with (2.45 Å) and without (3.10 Å) omecamtiv mecarbil bound. Omecamtiv mecarbil does not change the motor mechanism nor does it influence myosin structure. Instead, omecamtiv mecarbil binds to an allosteric site that stabilizes the lever arm in a primed position resulting in accumulation of cardiac myosin in the primed state prior to onset of cardiac contraction, thus increasing the number of heads that can bind to the actin filament and undergo a powerstroke once the cardiac cycle starts...
August 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28772011/brain-molecular-changes-and-behavioral-alterations-induced-by-propofol-anesthesia-exposure-in-peripubertal-rats
#16
Željko Pavković, Kosara Smiljanić, Selma Kanazir, Desanka Milanović, Vesna Pešić, Sabera Ruždijić
BACKGROUND: Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. AIM: In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. METHODS: The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca(2+) /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry...
September 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28770114/human-app-gene-expression-alters-active-zone-distribution-and-spontaneous-neurotransmitter-release-at-the-drosophila-larval-neuromuscular-junction
#17
Ekaterina A Saburova, Alexander N Vasiliev, Violetta V Kravtsova, Elena V Ryabova, Andrey L Zefirov, Olga I Bolshakova, Svetlana V Sarantseva, Igor I Krivoi
This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28768772/a-computational-combinatorial-approach-identifies-a-protein-inhibitor-of-superoxide-dismutase-1-misfolding-aggregation-and-cytotoxicity
#18
Victor Banerjee, Ofek Oren, Efrat Ben-Zeev, Ran Taube, Stanislav Engel, Niv Papo
Molecular agents that specifically bind and neutralize misfolded and toxic superoxide dismutase 1 (SOD1) mutant proteins may find application in attenuating the disease progression of familial amyotrophic lateral sclerosis (fALS). However, high structural similarities between the wild-type and mutant SOD1 proteins limit the utility of this approach. Here, we addressed this challenge by converting a promiscuous natural human IgG binding domain, the hyperthermophilic variant of protein G (HTB1), into a highly specific aggregation inhibitor (designated HTB1M) of two fALS-linked SOD1 mutants, SOD1G93A and SOD1G85R...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768746/oxygen-and-capacity-limited-thermal-tolerance-bridging-ecology-and-physiology
#19
REVIEW
Hans-O Pörtner, Christian Bock, Felix C Mark
Observations of climate impacts on ecosystems highlight the need for an understanding of organismal thermal ranges and their implications at the ecosystem level. Where changes in aquatic animal populations have been observed, the integrative concept of oxygen- and capacity-limited thermal tolerance (OCLTT) has successfully characterised the onset of thermal limits to performance and field abundance. The OCLTT concept addresses the molecular to whole-animal mechanisms that define thermal constraints on the capacity for oxygen supply to the organism in relation to oxygen demand...
August 1, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28767193/decreased-hippocampal-brain-derived-neurotrophic-factor-and-impaired-cognitive-function-by-hypoglossal-nerve-transection-in-rats
#20
Doyun Kim, Sena Chung, Seung-Hyun Lee, Se-Young Choi, Soung-Min Kim, JaeHyung Koo, Jong-Ho Lee, Jeong Won Jahng
The hypoglossal nerve controls tongue movements, and damages of it result in difficulty in mastication and food intake. Mastication has been reported to maintain hippocampus-dependent cognitive function. This study was conducted to examine the effect of tongue motor loss on the hippocampus-dependent cognitive function and its underlying mechanism. Male Sprague Dawley rats were subjected to the initial training of Morris water maze task before or after the bilateral transection of hypoglossal nerves (Hx). When the initial training was given before the surgery, the target quadrant dwelling time during the probe test performed at a week after the surgery was significantly reduced in Hx rats relative to sham-operated controls...
August 2, 2017: Journal of Cellular and Molecular Medicine
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