Otolithic receptor mechanisms for vestibular-evoked myogenic potentials: A review

Air-conducted sound and bone-conduced vibration activate otolithic receptors and afferent neurons in both the utricular and saccular maculae, and trigger small electromyographic (EMG) responses [called vestibular-evoked myogenic potentials (VEMPs)] in various muscle groups throughout the body. The use of these VEMPs for clinical assessment of human otolithic function is built on the following logical steps: (1) that high-frequency sound and vibration at clinically effective stimulus levels activate otolithic receptors and afferents, rather than semicircular canal afferents, (2) that there is differential anatomical projection of otolith afferents to eye muscles and neck muscles, and (3) that isolated stimulation of the utricular macula induces short latency responses in eye muscles, and that isolated stimulation of the saccular macula induces short latency responses in neck motoneurons. Evidence supports these logical steps, and so VEMPs are increasingly being used for clinical assessment of otolith function, even differential evaluation of utricular and saccular function. The proposal, originally put forward by Curthoys in 2010, is now accepted: that the ocular vestibular-evoked myogenic potential reflects predominantly contralateral utricular function and the cervical vestibular-evoked myogenic potential reflects predominantly ipsilateral saccular function. So VEMPs can provide differential tests of utricular and saccular function, not because of stimulus selectivity for either of the two maculae, but by measuring responses which are predominantly determined by the differential neural projection of utricular as opposed to saccular neural information to various muscle groups. The major question which this review addresses is how the otolithic sensory system, with such a high density otoconial layer, can be activated by individual cycles of sound and vibration and show such tight locking of the timing of action potentials of single primary otolithic afferents to a particular phase angle of the stimulus cycle even at frequencies far above 1,000 Hz. The new explanation is that it is due to the otoliths acting as seismometers at high frequencies and accelerometers at low frequencies. VEMPs are an otolith-dominated response, but in a particular clinical condition, semicircular canal dehiscence, semicircular canal receptors are also activated by sound and vibration, and act to enhance the otolith-dominated VEMP responses

Supramaximal calcium signaling triggers procoagulant platelet formation.

Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some platelets to become procoagulant, using the high-affinity Ca2+ indicator Fluo-4, which may become saturated during platelet stimulation, or low-affinity Fluo-5N, which reports only very high cytosolic Ca2+ concentrations. All activated platelets had high Fluo-4 fluorescence. However, in Fluo-5N-loaded platelets, only the procoagulant platelets had high fluorescence, indicating very high cytosolic Ca2+. This finding indicates a novel, "supramaximal" Ca2+ signal in procoagulant platelets (ie, much higher than normally considered maximal). Supramaximal Ca2+ signaling and the percentage of procoagulant platelets were inhibited by cyclosporin A, a mitochondrial permeability transition pore blocker, and Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, with no effect on Fluo-4 fluorescence. In contrast, Synta-66, an Orai1 blocker, reduced Fluo-4 fluorescence but did not directly inhibit generation of the supramaximal Ca2+ signal. Our findings show a distinct pattern of Ca2+ signaling in procoagulant platelets and provide a new framework to interpret the role of platelet signaling pathways in procoagulant platelets. This requires reassessment of the role of different Ca2+ channels and may provide new targets to prevent formation of procoagulant platelets and limit thrombosis

A mechanistic account of bodily resonance and implicit bias

Implicit social biases play a critical role in shaping our attitudes towards other people. Such biases are thought to arise, in part, from a comparison between features of one's own self-image and those of another agent, a process known as 'bodily resonance'. Recent data have demonstrated that implicit bias can be remarkably plastic, being modulated by brief immersive virtual reality experiences that place participants in a virtual body with features of an out-group member. Here, we provide a mechanistic account of bodily resonance and implicit bias in terms of a putative self-image network that encodes associations between different features of an agent. When subsequently perceiving another agent, the output of this self-image network is proportional to the overlap between their respective features, providing an index of bodily resonance. By combining the self-image network with a drift diffusion model of decision making, we simulate performance on the implicit association test (IAT) and show that the model captures the ubiquitous implicit bias towards in-group members. We subsequently demonstrate that this implicit bias can be modulated by a simulated illusory body ownership experience, consistent with empirical data; and that the magnitude and plasticity of implicit bias correlates with self-esteem. Hence, we provide a simple mechanistic account of bodily resonance and implicit bias which could contribute to the development of interventions for reducing the negative evaluation of social out-groups

Warped Tachyonic Inflation in Type IIB Flux Compactifications and the Open-String Completeness Conjecture

We consider a cosmological scenario within the KKLT framework for moduli stabilization in string theory. The universal open string tachyon of decaying non-BPS D-brane configurations is proposed to drive eternal topological inflation. Flux-induced `warping' can provide the small slow-roll parameters needed for successful inflation. Constraints on the parameter space leading to sufficient number of e-folds, exit from inflation, density perturbations and stabilization of the Kahler modulus are investigated. The conditions are difficult to satisfy in Klebanov-Strassler throats but can be satisfied in T^3 fibrations and other generic Calabi-Yau manifolds. This requires large volume and magnetic fluxes on the D-brane. The end of inflation may or may not lead to cosmic strings depending on the original non-BPS configuration. A careful investigation of initial conditions leading to a phenomenologically viable model for inflation is carried out. The initial conditions are chosen on the basis of Sen's open string completeness conjecture. We find time symmetrical bounce solutions without initial singularities for k=1 FRW models which are correlated with an inflationary period. Singular big-bang/big-crunch solutions also exist but do not lead to inflation. There is an intriguing correlation between having an inflationary universe in 4 dimensions and 6 compact dimensions or a big-crunch singularity and decompactification.Comment: 43 pages, 9 figures. v3: Typos correcte

Gauge Invariance and Finite Temperature Effective Actions of Chern-Simons Gauge Theories with Fermions

We discuss the behavior of theories of fermions coupled to Chern-Simons gauge fields with a non-abelian gauge group in three dimensions and at finite temperature. Using non-perturbative arguments and gauge invariance, and in contradiction with perturbative results, we show that the coefficient of the Chern-Simons term of the effective actions for the gauge fields at finite temperature can be {\it at most} an integer function of the temperature. This is in a sense a generalized no-renormalization theorem. We also discuss the case of abelian theories and give indications that a similar condition should hold there too. We discuss consequences of our results to the thermodynamics of anyon superfluids and fractional quantum Hall systems.Comment: Revtex, multico

Construction and biological characterization of an HB-GAM/FGF-1 chimera for vascular tissue engineering

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Isolation of DNA markers from a region between incontinentia pigmenti 1 (IP1) X-chromosomal translocation breakpoints by a comparative PCR analysis of a radiation hybrid subclone mapping panel

A strategy based on the use of human-specific interspersed repetitive sequence (IRS)-PCR amplification was used to isolate regional DNA markers in the vicinity of the incontinentia pigmenti 1 (IP1) locus. A radiation hybrid (RH) resulting from a fusion of an irradiated X-only somatic cell hybrid (C12D) and a thymidine kinase deficient (TK-) hamster cell line (a23) was identified as containing multiple X chromosome fragments, including DNA markers spanning IP1 X-chromosomal translocation breakpoints within region Xp11.21. From this RH, a panel of subclones was constructed and analyzed by IRS-PCR amplification to (a) identify subclones containing a reduced number of X chromosome fragments spanning the IP1 breakpoints and (b) construct a mapping panel to assist in identifying regional DNA markers in the vicinity of the IP1 locus. By using this strategy, we have isolated three different IRS-PCR amplification products that map to a region between IP1 X chromosome translocation breakpoints. A total of nine DNA sequences have now been mapped to this region; using these DNA markers for PFGE analyses, we obtained a probe order DXS14-DXS422-MTHFDL1-DXS705. These DNA markers provide a starting point for identifying overlapping genomic sequences spanning the IP1 translocation breakpoints; the availability of IP1 translocation breakpoints should assist the molecular analysis of this locus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29765/1/0000103.pd

On D3-brane Potentials in Compactifications with Fluxes and Wrapped D-branes

We study the potential governing D3-brane motion in a warped throat region of a string compactification with internal fluxes and wrapped D-branes. If the Kahler moduli of the compact space are stabilized by nonperturbative effects, a D3-brane experiences a force due to its interaction with D-branes wrapping certain four-cycles. We compute this interaction, as a correction to the warped four-cycle volume, using explicit throat backgrounds in supergravity. This amounts to a closed-string channel computation of the loop corrections to the nonperturbative superpotential that stabilizes the volume. We demonstrate for warped conical spaces that the superpotential correction is given by the embedding equation specifying the wrapped four-cycle, in agreement with the general form proposed by Ganor. Our approach automatically provides a solution to the problem of defining a holomorphic gauge coupling on wrapped D7-branes in a background with D3-branes. Finally, our results have applications to cosmological inflation models in which the inflaton is modeled by a D3-brane moving in a warped throat.Comment: 45 pages, 1 figure; v2: added reference, clarified notatio

Moduli Stabilisation and de Sitter String Vacua from Magnetised D7 Branes

Anomalous U(1)'s are ubiquitous in 4D chiral string models. Their presence crucially affects the process of moduli stabilisation and cannot be neglected in realistic set-ups. Their net effect in the 4D effective action is to induce a matter field dependence in the non-perturbative superpotential and a Fayet-Iliopoulos D-term. We study flux compactifications of IIB string theory in the presence of magnetised D7 branes. These give rise to anomalous U(1)'s that modify the standard moduli stabilisation procedure. We consider simple orientifold models to determine the matter field spectrum and the form of the effective field theory. We apply our results to one-modulus KKLT and multi-moduli large volume scenarios, in particular to the Calabi-Yau P^4_{[1,1,1,6,9]}. After stabilising the matter fields, the effective action for the Kahler moduli can acquire an extra positive term that can be used for de Sitter lifting with non-vanishing F- and D-terms. This provides an explicit realization of the D-term lifting proposal of hep-th/0309187.Comment: 35 pages, 1 figure. v2: Minor changes, references adde

Alu element in the RNA binding motif protein, X-linked 2 (RBMX2) gene found to be linked to bipolar disorder

Objective We have used long-read single molecule, real-time (SMRT) sequencing to fully characterize a similar to 12Mb genomic region on chromosome Xq24-q27, significantly linked to bipolar disorder (BD) in an extended family from a genetic sub-isolate. This family segregates BD in at least four generations with 24 affected individuals. Methods We selected 16 family members for targeted sequencing. The selected individuals either carried the disease haplotype, were non-carriers of the disease haplotype, or served as married-in controls. We designed hybrid capture probes enriching for 5-9Kb fragments spanning the entire 12Mb region that were then sequenced to screen for candidate structural variants (SVs) that could explain the increased risk for BD in this extended family. Results Altogether, 201 variants were detected in the critically linked region. Although most of these represented common variants, three variants emerged that showed near-perfect segregation among all BD type I affected individuals. Two of the SVs were identified in or near genes belonging to the RNA Binding Motif Protein, X-Linked (RBMX) gene family-a 330bp Alu (subfamily AluYa5) deletion in intron 3 of the RBMX2 gene and an intergenic 27bp tandem repeat deletion between the RBMX and G protein-coupled receptor 101 (GPR101) genes. The third SV was a 50bp tandem repeat insertion in intron 1 of the Coagulation Factor IX (F9) gene. Conclusions Among the three genetically linked SVs, additional evidence supported the Alu element deletion in RBMX2 as the leading candidate for contributing directly to the disease development of BD type I in this extended family.Peer reviewe