1,368,397 research outputs found

    Riluzole: What It Does to Spinal and Brainstem Neurons and How It Does It

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    Amyotrophic lateral sclerosis (Lou Gehrig's disease) is a devastating neurodegenerative disorder for which the only licensed treatment is riluzole. Although riluzole clinical efficacy is rather limited, its use has important implications for identifying those parameters that might improve its clinical benefits (dose, timing, disease stage) and for its offlabel administration in other neurodegenerative diseases, such as spinal cord injury. Studies of riluzole also have an intrinsically heuristic value to unveil mechanisms regulating the excitability of brain and spinal neurons because this drug is a pharmacological tool to probe the function of certain ion channels, or to study neurotransmitter release processes, and intracellular neuroprotective pathways. The present review focuses on how riluzole acts on brain and spinal neurons within motor networks, what mechanisms can be deduced from its effects, and what conditions may favor its use to contrast neurodegeneration or to ameliorate late symptoms like spasticity. Taking as an example the experimental neurodegeneration caused by overactivation of glutamatergic synapses (excitotoxicity), it seems likely that protection of motor networks by riluzole involves selected administration timing and dosing to target processes for releasing glutamate from very active synapses or for dampening repetitive firing by hyperfunctional motor cells. © The Author(s) 2012

    A repertoire of rhythmic bursting produced by hypoglossal motoneurons in physiological and pathological conditions

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    The brainstem nucleus hypoglossus contains motoneurons that provide the exclusive motor nerve supply to the tongue. In addition to voluntary tongue movements, tongue muscles rhythmically contract during a wide range of physiological activities, such as respiration, swallowing, chewing and sucking. Hypoglossal motoneurons are destroyed early in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease often associated with a deficit in the transport system of the neurotransmitter glutamate. The present study shows how periodic electrical discharges of motoneurons are mainly produced by a neuronal network that drives them into bursting mode via glutamatergic excitatory synapses. Burst activity is, however, modulated by the intrinsic properties of motoneurons that collectively synchronize their discharges via gap junctions to create ‘group bursters’. When glial uptake of glutamate is blocked, a distinct form of pathological bursting spontaneously emerges and leads to motoneuron death. Conversely, H2O2-induced oxidative stress strongly increases motoneuron excitability without eliciting bursting. Riluzole (the only drug currently licensed for the treatment of ALS) suppresses bursting of hypoglossal motoneurons caused by blockage of glutamate uptake and limits motoneuron death. These findings highlight how different patterns of electrical oscillations of brainstem motoneurons underpin not only certain physiological activities, but also motoneuron death induced by glutamate transporter impairment

    Hypoglossal motoneurons: a model to investigate physiological and pathophysiological properties of brainstem motoneurons

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    Hypoglossal motoneurons (HMs) are brainstem neurons that command rhytmic contraction of the tongue muscles during breathing as well as a variety of non-respiratory functions such as sleep, vocalization, suckling and swallowing. Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS; Lou-Gehrig disease) often damage HMs with distressing symptoms like dysarthria, dysphagia and breathing failure..

    Criptografia com Utilização de Cifra de Hill e Cifra Afim

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    Este trabalho consiste no estudo de dois métodos criptográficos de substituição Cifra de Hill e Cifra Afim, que servirão de auxilio ao estudo da matemática, incentivando atividades que estão relacionadas com a Teoria dos Números, envolvendo Números Inteiros, Divisibilidade, Números Primos e Congruência com os Números Inteiros mostrando suas aplicabilidades. Trabalharemos estes métodos voltados para Z_{26} que será análogo para Z{n

    Electro-Acoustic Behavior of the Mitotic Spindle: A Semi-Classical Coarse-Grained Model

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    The regulation of chromosome separation during mitosis is not fully understood yet. Microtubules forming mitotic spindles are targets of treatment strategies which are aimed at (i) the triggering of the apoptosis or (ii) the interruption of uncontrolled cell division. Despite these facts, only few physical models relating to the dynamics of mitotic spindles exist up to now. In this paper, we present the first electromechanical model which enables calculation of the electromagnetic field coupled to acoustic vibrations of the mitotic spindle. This electromagnetic field originates from the electrical polarity of microtubules which form the mitotic spindle. The model is based on the approximation of resonantly vibrating microtubules by a network of oscillating electric dipoles. Our computational results predict the existence of a rapidly changing electric field which is generated by either driven or endogenous vibrations of the mitotic spindle. For certain values of parameters, the intensity of the electric field and its gradient reach values which may exert a not-inconsiderable force on chromosomes which are aligned in the spindle midzone. Our model may describe possible mechanisms of the effects of ultra-short electrical and mechanical pulses on dividing cells - a strategy used in novel methods for cancer treatment. © 2014 Havelka et al

    A rejtett cifra szín genetikai módszerrel való kimutatása mudi fajtában

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    A kutyák cifra (Merle: rigó) színét egy retrotranszpozon beépülése okozza a SILV génbe, melynek eredménye az eumelanint termelő pigmentsejtek elégtelen működése. Homozigóta (MM) egyedekben gyakran fordulnak elő veleszületett látás- és hallásproblémák, ezért a heterozigóta (Mm) egyedek egymással történő párosítása nem javasolt, az érintett fajtáknál – így többek között a mudinál – pedig tiltott. Egyes színeket (pl. krém, bézs, fakó) azonban teljes egészében a feomelanin pigment határoz meg, melyre a merle génnek nincs hatása, így a heterozigóta egyedek fenotípusosan nem felismerhetőek (rejtett cifra). Hagyományosan a rejtett cifra egyedek csak az utánuk születő cifra utódok alapján azonosíthatók biztosan, de a tesztpárosítás nem tekinthető megbízható módszernek. Célunk egy gyors, megbízható és költséghatékony genetikai módszer tesztelése volt a mudi fajtában, mivel náluk a cifra szín mellett a fehér és a fakó szín is előfordul, növelve ezzel a rejtett cifra egyedek előfordulásának esélyét

    A1810 raw data

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    <p>Molecular dynamics simulation trajectories of kinesin motor domain exposed to electric field and the starting structure (<a href="https://zenodo.org/api/files/867c84b7-2f7b-4f33-ab01-ebba2d3e2dfe/system.gro?versionId=c2cc81fd-4605-4029-b2b2-01a4121d8659">system.gro</a>). </p> <p><strong>List of the files</strong></p> <ul> <li>system.gro – the initial structure of the system</li> </ul> <p> </p> <p><em>Trajectories, kinesin recentered</em></p> <p>trajectories with no electric field applied</p> <ul> <li>NOFIELD-traj_1_cent.xtc</li> <li>NOFIELD-traj_2_cent.xtc</li> <li>NOFIELD-traj_3_cent.xtc</li> </ul> <p> </p> <p>trajectories with 100 MV/m electric field in X direction</p> <ul> <li>X-traj_1_cent.xtc</li> <li>X-traj_2_cent.xtc</li> <li>X-traj_3_cent.xtc</li> </ul> <p>trajectories with 100 MV/m electric field in -X direction</p> <ul> <li>Xrev-traj_1_cent.xtc </li> <li>Xrev-traj_2_cent.xtc</li> <li>Xrev-traj_3_cent.xtc</li> </ul> <p>trajectories with 100 MV/m electric field in Y direction</p> <ul> <li>Y-traj_1_cent.xtc</li> <li>Y-traj_2_cent.xtc</li> <li>Y-traj_3_cent.xtc</li> </ul> <p>trajectories with 100 MV/m electric field in -Y direction</p> <ul> <li>Yrev-traj_1_cent.xtc</li> <li>Yrev-traj_2_cent.xtc</li> <li>Yrev-traj_3_cent.xtc</li> </ul&gt
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