4,906 research outputs found

    The brainstem reticular formation is a small-world, not scale-free, network

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    Recently, it has been demonstrated that several complex systems may have simple graph-theoretic characterizations as so-called ‘small-world’ and ‘scale-free’ networks. These networks have also been applied to the gross neural connectivity between primate cortical areas and the nervous system of Caenorhabditis elegans. Here, we extend this work to a specific neural circuit of the vertebrate brain—the medial reticular formation (RF) of the brainstem—and, in doing so, we have made three key contributions. First, this work constitutes the first model (and quantitative review) of this important brain structure for over three decades. Second, we have developed the first graph-theoretic analysis of vertebrate brain connectivity at the neural network level. Third, we propose simple metrics to quantitatively assess the extent to which the networks studied are small-world or scale-free. We conclude that the medial RF is configured to create small-world (implying coherent rapid-processing capabilities), but not scale-free, type networks under assumptions which are amenable to quantitative measurement

    Silk-inspired polymers and proteins

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    The biocompatibility and biodegradability of natural silk fibres and the benign conditions under which they (with impressive mechanical properties) are produced represent a biomimetic ideal. This ideal has inspired people in both academia and industry to prepare silk-mimetic polymers and proteins by chemical and/or biotechnological means. in the present paper, we aim to give an overview of the design principles of such silk-inspired polymers/proteins, their processing into various materials morphologies, their mechanical and biological properties, and, finally, their technical and biomedical applications.</p

    Emotion in the German Lutheran Baroque and the development of subjective time consciousness

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    This study examines some of the ways in which it was possible to understand emotion in Lutheran church music of the seventeenth and early eighteenth centuries. It suggests that emotion related to music more through association and contextual factors than through a fixed relationship, thus explaining the ways in which musical passages and techniques could be taken from a secular context to serve a sacred purpose. With these factors in mind, it is possible to suggest ways in which a listener's likely emotional association with music can be harnessed through particular compositional procedures. Schütz's setting of part of the Song of Songs may well engage with the listener's consciousness over time, stretching it and reinforcing the ‘useful’ emotional associations that the sacred context might bring. The opening aria of Bach's cantata ‘Liebster Jesu, mein Verlangen’ achieves something similar over a longer span and with greater emotional intensity. Here there is the added sense of the believer finding, losing and then rediscovering the object of spiritual adoration. The music thus implies the potential alienation of the listener, something both supported and overcome through the very structuring of the music. Its repetitive ritornello process is sometimes hidden but always latent, thus playing on the potential for subconscious recognition. Together, these two examples suggest that music can be used as a powerful demonstration of the historical development of modern forms of consciousness as related to emotional states over time

    Is there an integrative center in the vertebrate brain-stem? A robotic evaluation of a model of the reticular formation viewed as an action selection device

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    Neurobehavioral data from intact, decerebrate, and neonatal rats, suggests that the reticular formation provides a brainstem substrate for action selection in the vertebrate central nervous system. In this article, Kilmer, McCulloch and Blum’s (1969, 1997) landmark reticular formation model is described and re-evaluated, both in simulation and, for the first time, as a mobile robot controller. Particular model configurations are found to provide effective action selection mechanisms in a robot survival task using either simulated or physical robots. The model’s competence is dependent on the organization of afferents from model sensory systems, and a genetic algorithm search identified a class of afferent configurations which have long survival times. The results support our proposal that the reticular formation evolved to provide effective arbitration between innate behaviors and, with the forebrain basal ganglia, may constitute the integrative, ’centrencephalic’ core of vertebrate brain architecture. Additionally, the results demonstrate that the Kilmer et al. model provides an alternative form of robot controller to those usually considered in the adaptive behavior literature

    Acidic Residues Control the Dimerization of the N-terminal Domain of Black Widow Spiders’ Major Ampullate Spidroin 1

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    Dragline silk is the most prominent amongst spider silks and comprises two types of major ampullate spidroins (MaSp) differing in their proline content. In the natural spinning process, the conversion of soluble MaSp into a tough fiber is, amongst other factors, triggered by dimerization and conformational switching of their helical amino-terminal domains (NRN). Both processes are induced by protonation of acidic residues upon acidification along the spinning duct. Here, the structure and monomer-dimer-equilibrium of the domain NRN1 of Latrodectus hesperus MaSp1 and variants thereof have been investigated, and the key residues for both could be identified. Changes in ionic composition and strength within the spinning duct enable electrostatic interactions between the acidic and basic pole of two monomers which prearrange into an antiparallel dimer. Upon naturally occurring acidification this dimer is stabilized by protonation of residue E114. A conformational change is independently triggered by protonation of clustered acidic residues (D39, E76, E81). Such step-by-step mechanism allows a controlled spidroin assembly in a pH- and salt sensitive manner, preventing premature aggregation of spider silk proteins in the gland and at the same time ensuring fast and efficient dimer formation and stabilization on demand in the spinning duct

    Identification of the N-terminal Peptide Binding Site of Glucose-regulated Protein 94

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    Because the stress protein GRP94 can augment presentation of peptides to T cells, it is important to define how it, as well as all other HSP90 family members, binds peptides. Having previously shown that the N-terminal half of GRP94 can account for the peptide binding activity of the full-length protein, we now locate this binding site by testing predictions of a molecular docking model. The best predicted site was on the opposite face of the β sheet from the pan-HSP90 radicicol-binding pocket, in close proximity to a deep hydrophobic pocket. The peptide and radicicol-binding sites are distinct, as shown by the ability of a radicicol-refractive mutant to bind peptide. When the fluorophore acrylodan is attached to Cys(117)within the hydrophobic pocket, its fluorescence is reduced upon peptide binding, consistent with proximity of the two ligands. Substitution of His(125), which contacts the bound peptide, compromises peptide-binding activity. We conclude that peptide binds to the concave face of the β sheet of the N-terminal domain, where binding is regulated during the action cycle of the chaperone

    Do Matrix Metalloproteases and Tissue Inhibitors of Metalloproteases in Tenocytes of the Rotator Cuff Differ with Varying Donor Characteristics?

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    An imbalance between matrix metalloproteases (MMPs) and the tissue inhibitors of metalloproteases (TIMPs) may have a negative impact on the healing of rotator cuff tears. The aim of the project was to assess a possible relationship between clinical and radiographic characteristics of patients such as the age, sex, as well as the degenerative status of the tendon and the MMPs and TIMPs in their tenocyte-like cells (TLCs). TLCs were isolated from ruptured supraspinatus tendons and quantitative Real-Time PCR and ELISA was performed to analyze the expression and secretion of MMPs and TIMPs. In the present study, MMPs, mostly gelatinases and collagenases such as MMP-2, -9 and -13 showed an increased expression and protein secretion in TLCs of donors with higher age or degenerative status of the tendon. Furthermore, the expression and secretion of TIMP-1, -2 and -3 was enhanced with age, muscle fatty infiltration and tear size. The interaction between MMPs and TIMPs is a complex process, since TIMPs are not only inhibitors, but also activators of MMPs. This study shows that MMPs and TIMPs might play an important role in degenerative tendon pathologies

    Impact of lattice dynamics on the phase stability of metamagnetic FeRh: Bulk and thin films

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    We present phonon dispersions, element-resolved vibrational density of states (VDOS) and corresponding thermodynamic properties obtained by a combination of density functional theory (DFT) and nuclear resonant inelastic X-ray scattering (NRIXS) across the metamagnetic transition of B2 FeRh in the bulk material and thin epitaxial films. We see distinct differences in the VDOS of the antiferromagnetic (AF) and ferromagnetic (FM) phase which provide a microscopic proof of strong spin-phonon coupling in FeRh. The FM VDOS exhibits a particular sensitivity to the slight tetragonal distortions present in epitaxial films, which is not encountered in the AF phase. This results in a notable change in lattice entropy, which is important for the comparison between thin film and bulk results. Our calculations confirm the recently reported lattice instability in the AF phase. The imaginary frequencies at the XX-point depend critically on the Fe magnetic moment and atomic volume. Analyzing these non vibrational modes leads to the discovery of a stable monoclinic ground state structure which is robustly predicted from DFT but not verified in our thin film experiments. Specific heat, entropy and free energy calculated within the quasiharmonic approximation suggest that the new phase is possibly suppressed because of its relatively smaller lattice entropy. In the bulk phase, lattice degrees of freedom contribute with the same sign and in similar magnitude to the isostructural AF-FM phase transition as the electronic and magnetic subsystems and therefore needs to be included in thermodynamic modeling.Comment: 15 pages, 12 figure
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