2,988 research outputs found

    Modification of Loop 1 Affects the Nucleotide Binding Properties of Myo1c, the Adaptation Motor in the Inner Ear

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    Myo1c is one of eight members of the mammalian myosin I family of actin-associated molecular motors. In stereocilia of the hair cells in the inner ear, Myo1c presumably serves as the adaptation motor, which regulates the opening and closing of transduction channels. Although there is conservation of sequence and structure among all myosins in the N-terminal motor domain, which contains the nucleotide- and actin-binding sites, some differences include the length and composition of surface loops, including loop 1, which lies near the nucleotide-binding domain. To investigate the role of loop 1, we expressed in insect cells mutants of a truncated form of Myo1c, Myo1c1IQ, as well as chimeras of Myo1c1IQ with the analogous loop from other myosins. We found that replacement of the charged residues in loop 1 with alanines or the whole loop with a series of alanines did not alter the ATPase activity, transient kinetics properties, or Ca2+ sensitivity of Myo1c1IQ. Substitution of loop 1 with that of the corresponding region from tonic smooth muscle myosin II (Myo1c1IQ-tonic) or replacement with a single glycine (Myo1c1IQ-G) accelerated the release of ADP from A.M 2?3-fold in Ca2+, whereas substitution with loop 1 from phasic muscle myosin II (Myo1c1IQ-phasic) accelerated the release of ADP 35-fold. Motility assays with chimeras containing a single ?-helix, or SAH, domain showed that Myo1cSAH-tonic translocated actin in vitro twice as fast as Myo1cSAH-WT and 3-fold faster than Myo1cSAH-G. The studies show that changes induced in Myo1c via modification of loop 1 showed no resemblance to the behavior of the loop donor myosins or to the changes previously observed with similar Myo1b chimeras

    Qualification of the most statistically "sensitive" diffusion tensor imaging parameters for detection of spinal cord injury

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    Qualification of the most statistically "sensitive" diffusion parameters using Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) of the control and injured spinal cord of a rat in vivo and in vitro after the trauma is reported. Injury was induced in TH12/TH13 level by a controlled "weight-drop". In vitro experiments were performed in a home-built MR microscope, with a 6.4 T magnet, in vivo samples were measured in a 9.4 T/21 horizontal magnet The aim of this work was to find the most effective diffusion parameters which are useful in the statistically significant detection of spinal cord tissue damage. Apparent diffusion tensor (ADT) weighted data measured in vivo and in vitro on control and injured rat spinal cord (RSC) in the transverse planes and analysis of the diffusion anisotropy as a function of many parameters, which allows statisticall expose of the existence of the damage are reported

    Endplate calcification and cervical intervertebral disc degeneration: the role of endplate marrow contact channel occlusion

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    Background: The aim of this study was to determine the fundamental relationships between cervical intervertebral disc (IVD) degeneration, endplate calcification, and the patency of endplate marrow contact channels (MCC). Materials and methods: Sixty cervical IVDs were excised from 30 human cadavers. After sectioning the specimens underwent micro computed tomography (microCT) — from all images the number, calibre, diameter and distribution of endplate openings were measured using ImageJ. Next, the specimens were scored for macroscopic degeneration (Thompson’s classification), and subsequently underwent histological analysis for both IVD and endplate degeneration (Boos’s classification) and calcification. Results: The study group comprised 30 female and 30 male IVDs (mean age ± SD: 51.4 ± 19.5). Specimen’s age, macroscopic and microscopic degeneration correlated negatively with the number of MCCs (r = –0.33–(–0.95); p < 0.0001), apart from the MCCs > 300 μm in diameter (r = 0.66–0.79; p < 0.0001). The negative relationship was strongest for the MCCs 10–50 μm in diameter. Conclusions: There is a strong negative correlation between the number of endplate MCCs, and both macroscopic and microscopic cervical IVD and endplate degeneration. This could further support the thesis that endplate calcification, through the occlusion of MCCs, leads to a fall in nutrient transport to the IVD, and subsequently causes its degeneration

    Full Field Computing for Elastic Pulse Dispersion in Inhomogeneous Bars

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    In the paper, the finite element method and the finite volume method are used in parallel for the simulation of a pulse propagation in periodically layered composites beyond the validity of homogenization methods. The direct numerical integration of a pulse propagation demonstrates dispersion effects and dynamic stress redistribution in physical space on example of a one-dimensional layered bar. Results of numerical simulations are compared with analytical solution constructed specifically for the considered problem. Analytical solution as well as numerical computations show the strong influence of the composition of constituents on the dispersion of a pulse in a heterogeneous bar and the equivalence of results obtained by two numerical methods

    Contact processes with long-range interactions

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    A class of non-local contact processes is introduced and studied using mean-field approximation and numerical simulations. In these processes particles are created at a rate which decays algebraically with the distance from the nearest particle. It is found that the transition into the absorbing state is continuous and is characterized by continuously varying critical exponents. This model differs from the previously studied non-local directed percolation model, where particles are created by unrestricted Levy flights. It is motivated by recent studies of non-equilibrium wetting indicating that this type of non-local processes play a role in the unbinding transition. Other non-local processes which have been suggested to exist within the context of wetting are considered as well.Comment: Accepted with minor revisions by Journal of Statistical Mechanics: Theory and experiment

    Non Sequential Recursive Pair Substitution: Some Rigorous Results

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    We present rigorous results on some open questions on NSRPS, non sequential recursive pairs substitution method (see Grassberger in \cite{G}). In particular, starting from the action of NSRPS on finite strings we define a corresponding natural action on measures and we prove that the iterated measure becomes asymptotically Markov. This certify the effectiveness of NSRPS as a tool for data compression and entropy estimation.Comment: 20 page

    Type I interferon responses of common carp strains with different levels of resistance to koi herpesvirus disease during infection with CyHV-3 or SVCV

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    Carp from breeding strains with different genetic background present diverse levels of resistance to viral pathogens. Carp strains of Asian origin, currently being treated as Cyprinus rubrofuscus L., especially Amur wild carp (AS), were proven to be more resistant to koi herpesvirus disease (KHVD; caused by cyprinid herpesvirus 3, CyHV-3) than strains originating from Europe and belonging to Cyprinus carpio L., like the Prerov scale carp (PS) or koi carp from a breed in the Czech Republic. We hypothesised that it can be associated with a higher magnitude of type I interferon (IFN) response as a first line of innate defence mechanisms against viral infections. To evaluate this hypothesis, four strains of common carp (AS, Rop, PS and koi) were challenged using two viral infection models: Rhabdovirus SVCV (spring viremia of carp virus) and alloherpesvirus CyHV-3. The infection with SVCV induced a low mortality rate and the most resistant was the Rop strain (no mortalities), whereas the PS strain was the most susceptible (survival rate of 78%). During CyHV-3 infection, Rop and AS strains performed better (survival rates of 78% and 53%, respectively) than PS and koi strains (survival rates of 35% and 10%, respectively). The evaluation of virus loads and virus replication showed significant differences between the carp strains, which correlated with the mortality rate. The evaluation of type I IFN responses showed that there were fundamental differences between the virus infection models. While responses to the SVCV were high, the CyHV-3 generally induced low responses. Furthermore, the results demonstrated that the magnitude of type I IFN responses did not correlate with a higher resistance in infected carp. In the case of a CyHV-3 infection, reduced type I IFN responses could be related to the potential ability of the virus to interfere with cellular sensing of foreign nucleic acids. Taken together, the results broaden our understanding of how common carp from different genetic lines interact with various viral pathogens

    A status report on the observability of cosmic bubble collisions

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    In the picture of eternal inflation as driven by a scalar potential with multiple minima, our observable universe resides inside one of many bubbles formed from transitions out of a false vacuum. These bubbles necessarily collide, upsetting the homogeneity and isotropy of our bubble interior, and possibly leading to detectable signatures in the observable portion of our bubble, potentially in the Cosmic Microwave Background or other precision cosmological probes. This constitutes a direct experimental test of eternal inflation and the landscape of string theory vacua. Assessing this possibility roughly splits into answering three questions: What happens in a generic bubble collision? What observational effects might be expected? How likely are we to observe a collision? In this review we report the current progress on each of these questions, improve upon a few of the existing results, and attempt to lay out directions for future work.Comment: Review article; comments very welcome. 24 pages + 4 appendices; 19 color figures. (Revised version adds two figures, minor edits.
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