Practice makes perfect: the neural substrates of tactile discrimination by Mah-Jong experts include the primary visual cortex

Background

It has yet to be determined whether visual-tactile cross-modal plasticity due to visual deprivation, particularly in the primary visual cortex (V1), is solely due to visual deprivation or if it is a result of long-term tactile training. Here we conducted an fMRI study with normally-sighted participants who had undergone long-term training on the tactile shape discrimination of the two dimensional (2D) shapes on Mah-Jong tiles (Mah-Jong experts). Eight Mah-Jong experts and twelve healthy volunteers who were naïve to Mah-Jong performed a tactile shape matching task using Mah-Jong tiles with no visual input. Furthermore, seven out of eight experts performed a tactile shape matching task with unfamiliar 2D Braille characters.

Results

When participants performed tactile discrimination of Mah-Jong tiles, the left lateral occipital cortex (LO) and V1 were activated in the well-trained subjects. In the naïve subjects, the LO was activated but V1 was not activated. Both the LO and V1 of the well-trained subjects were activated during Braille tactile discrimination tasks.

Conclusion

The activation of V1 in subjects trained in tactile discrimination may represent altered cross-modal responses as a result of long-term training.     

Vaccine based on a ubiquitous cysteinyl protease and streptococcal pyrogenic exotoxin A protects against Streptococcus pyogenes sepsis and toxic shock

Background

The gram-positive bacterium Streptococcus pyogenes is a common pathogen of humans that causes invasive infections, toxic-shock syndrome, rheumatic fever, necrotizing fasciitis and other diseases. Detection of antibiotic resistance in clinical isolates has renewed interest in development of new vaccine approaches for control S. pyogenes sepsis. In the study presented, a novel protein vaccine was examined. The vaccine was based on a recombinant protein fusion between streptococcal pyrogenic exotoxin B (SpeB), a cysteinyl protease expressed by all clinical isolates, and streptococcal pyrogenic exotoxin A (SpeA), a superantigen produced by a large subset of isolates.

Results

A novel protein was produced by mutating the catalytic site of SpeB and the receptor binding surface of SpeA in a fusion of the two polypeptides. Vaccination of HLA-DQ8 transgenic mice with the SpeA-SpeB fusion protein protected against a challenge with the wild-type SpeA that was lethal to naïve controls, and vaccinated mice were protected from an otherwise lethal S. pyogenes infection.

Conclusion

These results suggest that the genetically attenuated SpeA-SpeB fusion protein may be useful for controlling S. pyogenes infections. Vaccination with the SpeA-SpeB fusion protein described in this study may potentially result in protective immunity against multiple isolates of S. pyogenes due to the extensive antibody cross-reactivity previously observed among all sequence variants of SpeB and the high frequency of SpeA-producing strains.     

Disturbed oscillatory brain dynamics in subcortical ischemic vascular dementia

Background

This study examined the effects of dietary polyunsaturated fatty acids (PUFA) as different n-6: n-3 ratios on spatial learning and gene expression of peroxisome- proliferator-activated receptors (PPARs) in the hippocampus of rats. Thirty male Sprague?CDawley rats were randomly allotted into 3 groups of ten animals each and received experimental diets with different n-6: n-3 PUFA ratios of either 65:1, 22:1 or 4.5:1. After 10?weeks, the spatial memory of the animals was assessed using the Morris Water Maze test. The expression of PPAR?? and PPAR?? genes were determined using real-time PCR.

Results

Decreasing dietary n-6: n-3 PUFA ratios improved the cognitive performance of animals in the Morris water maze test along with the upregulation of PPAR?? and PPAR?? gene expression. The animals with the lowest dietary n-6: n-3 PUFA ratio presented the highest spatial learning improvement and PPAR gene expression.

Conclusion

It can be concluded that modulation of n-6: n-3 PUFA ratios in the diet may lead to increased hippocampal PPAR gene expression and consequently improved spatial learning and memory in rats.     

Computational framework for the prediction of transcription factor binding sites by multiple data integration

Background

Activation of extracellular signal-regulated protein kinase (ERK), a member of mitogen-activated protein kinase (MAPK) family, has been proposed to mediate neurite outgrowth-promoting effects of several neurotrophic factors in vitro. However, the precise activity of ERK during axonal regeneration in vivo remains unclear. Peripheral axotomy has been shown to activate ERK in the cell bodies of primary afferent neurons and associated satellite cells. Nevertheless, whether ERK is also activated in the axons and surrounded Schwann cells which also play a key role in the regeneration process has not been clarified.

Results

Phosphorylation of ERK in the sciatic nerve in several time-points after crush injury has been examined. Higher phosphorylation of ERK was observed in the proximal and distal nerve stumps compared to the contralateral intact nerve from one day to one month after crush. The activation of ERK was mainly localized in the axons of the proximal segments. In the distal segments, however, active ERK was predominantly found in Schwann cells forming Bungner's bands.

Conclusion

The findings indicate that ERK is activated in both the proximal and distal nerve stumps following nerve injury. The role of activated ERK in Wallerian degeneration and subsequent regeneration in vivo remains to be elucidated.     

Inference of Kinetic Ising Model on Sparse Graphs

Based on dynamical cavity method, we propose an approach to the inference of kinetic Ising model, which asks to reconstruct couplings and external fields from given time-dependent output of original system. Our approach gives an exact result on tree graphs and a good approximation on sparse graphs, it can be seen as an extension of Belief Propagation inference of static Ising model to kinetic Ising model. While existing mean field methods to the kinetic Ising inference e.g., naïve mean-field, TAP equation and simply mean-field, use approximations which calculate magnetizations and correlations at time t from statistics of data at time t?1, dynamical cavity method can use statistics of data at times earlier than t?1 to capture more correlations at different time steps. Extensive numerical experiments show that our inference method is superior to existing mean-field approaches on diluted networks.     

Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain

Background

Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon.

Methods

For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants.

Results

We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression.

Conclusions

We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function.     

Der Grenzübergang zum starren Körper für das quantenmechanische Dreikörperproblem

It is a well known difficulty to introduce the concept of rigid body into quantum mechanics. The authors show how this problem may be solved rigorously for three particles by using a suitable set of coordinates. After subjecting the hamiltonian to a canonical transformation, the coupling term of rotational and vibrational motion vanishes in the limit of infinitesimal vibrational amplitudes, making them separable and thus leading back toWang's naïve quantum theory of the rigid body rotations.     

In Vitro Assessment of Tobacco Smoke Toxicity at the BBB: Do Antioxidant Supplements Have a Protective Role?

Background

Calcitonin gene-related peptide (CGRP) has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin), synaptophysin (synaptic vesicles) or IB4 (C-fibers in general) were performed.

Results

In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy.

Conclusions

This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1-level, and shows the possibility of CGRP acting postjunctionally in these areas putatively involved in primary headaches.     

Microcanonical Analysis of the Curie–Weiss Anisotropic Quantum Heisenberg Model in a Magnetic Field

The anisotropic quantum Heisenberg model with Curie-Weiss-type interactions is studied analytically in several variants of the microcanonical ensemble. (Non)equivalence of microcanonical and canonical ensembles is investigated by studying the concavity properties of entropies. The microcanonical entropy \(s(e,\varvec{m})\) is obtained as a function of the energy \(e\) and the magnetization vector \({\varvec{m}}\) in the thermodynamic limit. Since, for this model, \(e\) is uniquely determined by \({\varvec{m}}\) , the same information can be encoded either in \(s(\varvec{m})\) or \(s(e,m_1,m_2)\) . Although these two entropies correspond to the same physical setting of fixed \(e\) and \({\varvec{m}}\) , their concavity properties differ. The entropy \(s_{{\varvec{h}}}(u)\) , describing the model at fixed total energy \(u\) and in a homogeneous external magnetic field \({\varvec{h}}\) of arbitrary direction, is obtained by reduction from the nonconcave entropy \(s(e,m_1,m_2)\) . In doing so, concavity, and therefore equivalence of ensembles, is restored. \(s_{{\varvec{h}}}(u)\) has nonanalyticities on surfaces of co-dimension 1 in the \((u,\varvec{h})\) -space. Projecting these surfaces into lower-dimensional phase diagrams, we observe that the resulting phase transition lines are situated in the positive-temperature region for some parameter values, and in the negative-temperature region for others. In the canonical setting of a system coupled to a heat bath of positive temperatures, the nonanalyticities in the microcanonical negative-temperature region cannot be observed, and this leads to a situation of effective nonequivalence even when formal equivalence holds.     

Pyrid-2-yl and 2-CyanoPhenyl fused heterocyclic compounds as human P2X_{3} inhibitors: a combined approach based on homology modelling,docking and QSAR analysis

P2X receptors are hetero-oligomeric proteins that function as membrane ion channels and are gated by extracellular ATP. The hP2X $_{3}$ subunit is a constituent of the channels on a subset of sensory neurons involved in pain signaling, where ATP released by damaged and inflamed tissue can initiate action potentials. Hence, the inhibition of ATP-activated P2X $_{3}$ receptor is an exciting approach for the treatment of inflammatory and neuropathic pain. Recently, the crystal structures of zebrafish P2X $_{4}$ (zP2X $_{4})$ were obtained in closed, apo state (PDB ID: 3I5D) and ATP-bound, open state (PDB ID: 4DW1). These structures were used to develop a homology model of human P2X $_{3}$ (hP2X $_{3})$ in order to identify through docking studies, the binding modes of known P2X $_{3}$ inhibitors and their key active site interactions, along with a pharmacophore-based 3D-QSAR model for a series of 136 Pyrid-2-yl and 2-CyanoPhenyl fused heterocyclic compounds. These 3D-QSAR models have been developed with different combinations of training and test set divisions obtained by random separation, Jarvis–Patrick clustering, K-means clustering and sphere exclusion methods. The best predictive 3D-QSAR model resulted in training set R $^{2 }$ of 0.75, internal test set Q $^{2}$ of 0.74, Pearson-R value of 0.87 and root mean square error of 0.37. The information generated by the pharmacophore model and docking analyses using the homology model provides valuable clues to design novel potent hP2X $_{3}$ inhibitors.     

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

Background

Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve.

Results

Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia.

Conclusions

TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

     

Spectroscopy and lifetime measurement of high spin states in 73Se

The nucleus ⁷³ Se was studied by the reaction ⁵¹ V(²⁸ Si,αpn)⁷³ Se. The level scheme extended upto $\frac{{41}} {2}\bar h $ in both +ve and ?ve parity bands with 10 new transitions placed in the level scheme. Lifetimes of 17 high spin states measured by DSAM. The transitional quadrupole moment is found to drop down after the band crossing suggesting a less deformed configuration. At the band crossing region, Q _t increases suddenly in both +ve and ?ve parity bands. It is argued that the +ve parity band is a decoupled band.     

Localization in the ground state of the ising model with a random transverse field

We study the zero-temperature behavior of the Ising model in the presence of a random transverse field. The Hamiltonian is given by $$H = - J\sum\limits_{\left\langle {x,y} \right\rangle } {\sigma _3 (x)\sigma _3 (y) - \sum\limits_x {h(x)\sigma _1 (x)} } $$ whereJ>0,x,y∈Z ^d, σ₁, σ₃ are the usual Pauli spin 1/2 matrices, andh={h(x),x∈Z ^d} are independent identically distributed random variables. We consider the ground state correlation function 〈σ₃(x)σ₃(y)〉 and prove:

1. Letd be arbitrary. For anym>0 andJ sufficiently small we have, for almost every choice of the random transverse fieldh and everyx∈Z ^d, that $$\left\langle {\sigma _3 (x)\sigma _3 (y)} \right\rangle \leqq C_{x,h} e^{ - m\left| {x - y} \right|} $$ for ally∈Z ^d withC _{x h} <∞.
2. Letd≧2. IfJ is sufficiently large, then, for almost every choice of the random transverse fieldh, the model exhibits long range order, i.e., $$\mathop {\overline {\lim } }\limits_{\left| y \right| \to \infty } \left\langle {\sigma _3 (x)\sigma _3 (y)} \right\rangle > 0$$ for anyx∈Z ^d.

     

Dependence of electroweak parameters on the definition of the top-quark mass

The QCD corrections to electroweak parameters depend on the renormalization scheme and scales used to define the top-quark mass. We analyze these dependences for theW-boson mass predicted via Δr to ${\mathcal{O}}(\alpha \alpha _s )$ and ${\mathcal{O}}(\alpha \alpha _s^2 )$ in the on-shell and $\overline {MS} $ schemes. These variations provide us with a hint on the magnitude of the unknown higher-order QCD effects and contribute to the theoretical error of the prediction.     

Antihydrogen (hydrogen) atom formation

In this paper we show how the ATHENA data samples on the antihydrogen ( ${\bar{\rm H}}$ ) formation in very different conditions provide useful information on the two different possible mechanisms: the 3-body reaction ( $\bar{p}+{e^+}+{e^+}\rightarrow {\bar{\rm H}}+ e^+$ ) and the 2-body reaction ( $\bar{p}+{\rm e^+}\rightarrow {\bar{\rm H}}+{h\nu}$ ).     

The Distribution of the Area Under a Bessel Excursion and its Moments

A Bessel excursion is a Bessel process that begins at the origin and first returns there at some given time \(T\) . We study the distribution of the area under such an excursion, which recently found application in the context of laser cooling. The area \(A\) scales with the time as \(A \sim T^{3/2}\) , independent of the dimension, \(d\) , but the functional form of the distribution does depend on \(d\) . We demonstrate that for \(d=1\) , the distribution reduces as expected to the distribution for the area under a Brownian excursion, known as the Airy distribution, deriving a new expression for the Airy distribution in the process. We show that the distribution is symmetric in \(d-2\) , with nonanalytic behavior at \(d=2\) . We calculate the first and second moments of the distribution, as well as a particular fractional moment. We also analyze the analytic continuation from \(d<2\) to \(d>2\) . In the limit where \(d\rightarrow 4\) from below, this analytically continued distribution is described by a one-sided Lévy \(\alpha \) -stable distribution with index \(2/3\) and a scale factor proportional to \([(4-d)T]^{3/2}\) .     

Coupled-Channels Approach and Simple Models in the Theory of Exotic Atom Formation

Atomic collisions of slow negative particles X ^? (μ^?, $\bar p$ , etc.) are considered using coupled channels semiclassical approximation that takes into account 2- and 3-particle channels. Analytical expression for differential elastic cross section is proposed. Differential cross section reveals essential quantum interference effects. Inelastic $\bar p$ –Ne and $\bar p$ –Ar cross sections are considered using model potentials.     

Misalignment tolerance analysis and fabrication for highly efficient parallel optical-electrical convertor module

A compact, highly efficient, and passively assembled parallel optical-electrical convertor module (POECM) for active optical cable application is proposed. This paper presents our POECM structure, optical design simulation results, fabrication process, and data transmission test results, in sequence. The POECM has a compact size of \(18.5\hbox {mm} \times 10\hbox {mm} \times 2.8\hbox {mm}\) . We confirm a data rate of total throughput at 21.6 Gbps ( \(5.4\hbox {Gbps} \times 4\) channels) with a bit error rate of less than \(10^{-12}\) .