Measuring the effects of manipulating stimulus presentation time on sensorimotor alpha and low beta reactivity during hand movement observation

The present study addresses three methodological questions that have been ignored in previous research on EEG indices of the human mirror neuron system (hMNS), particularly in regard to autistic individuals. The first question regards how to elicit the EEG indexed hMNS during movement observation: Is hMNS activation best elicited using long stimulus presentations or multiple short repetitions? The second question regards what EEG sensorimotor frequency bands reflect sensorimotor reactivity during hand movement observation? The third question regards how widespread is the EEG reactivity over the sensorimotor cortex during movement observation? The present study explored sensorimotor alpha and low beta reactivity during hand movement versus static hand or bouncing balls observation and compared two experimental protocols (long exposure vs. multiple repetitions) in the same participants. Results using the multiple repetitions protocol indicated a greater low beta desynchronisation over the sensorimotor cortex during hand movement compared to static hand and bouncing balls observation. This result was not achieved using the long exposure protocol. Therefore, the present study suggests that the multiple repetitions protocol is a more robust protocol to use when exploring the sensorimotor reactivity induced by hand action observation. In addition, sensorimotor low beta desynchronisation was differently modulated during hand movement, static hand and bouncing balls observation (non-biological motion) while it was not the case for sensorimotor alpha and that suggest that low beta may be a more sensitive index of hMNS activation during biological motion observation. In conclusion the present study indicates that sensorimotor reactivity of low beta during hand movement observation was found to be more widespread over the sensorimotor cortex than previously thought.

Internal wave drag in stratified flow over mountains on a beta plane

The impact of the variation of the Coriolis parameter f on the drag exerted by internal Rossby-gravity waves on elliptical mountains is evaluated using linear theory, assuming constant wind and static stability and a beta-plane approximation. Previous calculations of inertia-gravity wave drag are thus extended in an attempt to establish a connection with existing studies on planetary wave drag, developed primarily for fluids topped by a rigid lid. It is found that the internal wave drag for zonal westerly flow strongly increases relative to that given by the calculation where f is assumed to be a constant, particularly at high latitudes and for mountains aligned meridionally. Drag increases with mountain width for sufficiently wide mountains, reaching values much larger than those valid in the non-rotating limit. This occurs because the drag receives contributions from a low wavenumber range, controlled by the beta effect, which accounts for the drag amplification found here. This drag amplification is shown to be considerable for idealized analogues of real mountain ranges, such as the Himalayas and the Rocky mountains, and comparable to the barotropic Rossby wave drag addressed in previous studies.

Endosomal endothelin-converting enzyme-1: a regulator of beta-arrestin-dependent ERK signaling

Neuropeptide signaling at the cell surface is regulated by metalloendopeptidases, which degrade peptides in the extracellular fluid, and beta-arrestins, which interact with G protein-coupled receptors (GPCRs) to mediate desensitization. beta-Arrestins also recruit GPCRs and mitogen-activated protein kinases to endosomes to allow internalized receptors to continue signaling, but the mechanisms regulating endosomal signaling are unknown. We report that endothelin-converting enzyme-1 (ECE-1) degrades substance P (SP) in early endosomes of epithelial cells and neurons to destabilize the endosomal mitogen-activated protein kinase signalosome and terminate signaling. ECE-1 inhibition caused endosomal retention of the SP neurokinin 1 receptor, beta-arrestins, and Src, resulting in markedly sustained ERK2 activation in the cytosol and nucleus, whereas ECE-1 overexpression attenuated ERK2 activation. ECE-1 inhibition also enhanced SP-induced expression and phosphorylation of the nuclear death receptor Nur77, resulting in cell death. Thus, endosomal ECE-1 attenuates ERK2-mediated SP signaling in the nucleus to prevent cell death. We propose that agonist availability in endosomes, here regulated by ECE-1, controls beta-arrestin-dependent signaling of endocytosed GPCRs.

Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins

Although cell surface metalloendopeptidases degrade neuropeptides in the extracellular fluid to terminate signaling, the function of peptidases in endosomes is unclear. We report that isoforms of endothelin-converting enzyme-1 (ECE-1a-d) are present in early endosomes, where they degrade neuropeptides and regulate post-endocytic sorting of receptors. Calcitonin gene-related peptide (CGRP) co-internalizes with calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), beta-arrestin2, and ECE-1 to early endosomes, where ECE-1 degrades CGRP. CGRP degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution to the cytosol. ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overexpression has the opposite effect. ECE-1 does not regulate either the resensitization of receptors for peptides that are not ECE-1 substrates (e.g., angiotensin II), or the recycling of the bradykinin B(2) receptor, which transiently interacts with beta-arrestins. We propose a mechanism by which endosomal ECE-1 degrades neuropeptides in endosomes to disrupt the peptide/receptor/beta-arrestin complex, freeing internalized receptors from beta-arrestins and promoting recycling and resensitization.

Mast cell tryptase controls paracellular permeability of the intestine: role of protease-activated receptor 2 and beta-arrestins

Tight junctions between intestinal epithelial cells prevent ingress of luminal macromolecules and bacteria and protect against inflammation and infection. During stress and inflammation, mast cells mediate increased mucosal permeability by unknown mechanisms. We hypothesized that mast cell tryptase cleaves protease-activated receptor 2 (PAR2) on colonocytes to increase paracellular permeability. Colonocytes expressed PAR2 mRNA and responded to PAR2 agonists with increased [Ca2+]i. Supernatant from degranulated mast cells increased [Ca2+]i in colonocytes, which was prevented by a tryptase inhibitor, and desensitized responses to PAR2 agonist, suggesting PAR2 cleavage. When applied to the basolateral surface of colonocytes, PAR2 agonists and mast cell supernatant decreased transepithelial resistance, increased transepithelial flux of macromolecules, and induced redistribution of tight junction ZO-1 and occludin and perijunctional F-actin. When mast cells were co-cultured with colonocytes, mast cell degranulation increased paracellular permeability of colonocytes. This was prevented by a tryptase inhibitor. We determined the role of ERK1/2 and of beta-arrestins, which recruit ERK1/2 to PAR2 in endosomes and retain ERK1/2 in the cytosol, on PAR2-mediated alterations in permeability. An ERK1/2 inhibitor abolished the effects of PAR2 agonist on permeability and redistribution of F-actin. Down-regulation of beta-arrestins with small interfering RNA inhibited PAR2-induced activation of ERK1/2 and suppressed PAR2-induced changes in permeability. Thus, mast cells signal to colonocytes in a paracrine manner by release of tryptase and activation of PAR2. PAR2 couples to beta-arrestin-dependent activation of ERK1/2, which regulates reorganization of perijunctional F-actin to increase epithelial permeability. These mechanisms may explain the increased epithelial permeability of the intestine during stress and inflammation.

Ethnic differences in beta-cell function, dietary intake and expression of the metabolic syndrome among UK adults of south Asian, black African-Caribbean and white-European origin at high risk of metabolic syndrome

A cross-sectional analysis of ethnic differences in dietary intake, insulin sensitivity and beta-cell function, using the intravenous glucose tolerance test (IVGTT), was conducted on 497 healthy adult participants of the ‘Reading, Imperial, Surrey, Cambridge, and Kings’ (RISCK) study. Insulin sensitivity (Si) was significantly lower in African-Caribbean (AC) and South Asian (SA) participants [IVGTT-Si; AC: 2.13 vs SA: 2.25 vs white-European (WE): 2.84 (×10−4 mL µU min)2, p < 0.001]. AC participants had a higher prevalence of anti-hypertensive therapy (AC: 19.7% vs SA: 7.5%), the most cardioprotective lipid profile [total:high-density lipoprotein (HDL); AC: 3.52 vs SA: 4.08 vs WE: 3.83, p = 0.03] and more pronounced hyperinsulinaemia [IVGTT–acute insulin response (AIR)] [AC: 575 vs SA: 428 vs WE: 344 mL/µU/min)2, p = 0.002], specifically in female participants. Intake of saturated fat and carbohydrate was lower and higher in AC (10.9% and 50.4%) and SA (11.1% and 52.3%), respectively, compared to WE (13.6% and 43.8%, p < 0.001). Insulin resistance in ACs is characterised by ‘normal’ lipid profiles but high rates of hypertension and pronounced hyperinsulinaemia.

Beta event-related desynchronization as an index of individual differences in processing human facial expression: further investigations of autistic traits in typically developing adults

The human mirror neuron system (hMNS) has been associated with various forms of social cognition and affective processing including vicarious experience. It has also been proposed that a faulty hMNS may underlie some of the deficits seen in the autism spectrum disorders (ASDs). In the present study we set out to investigate whether emotional facial expressions could modulate a putative EEG index of hMNS activation (mu suppression) and if so, would this differ according to the individual level of autistic traits [high versus low Autism Spectrum Quotient (AQ) score]. Participants were presented with 3 s films of actors opening and closing their hands (classic hMNS mu-suppression protocol) while simultaneously wearing happy, angry, or neutral expressions. Mu-suppression was measured in the alpha and low beta bands. The low AQ group displayed greater low beta event-related desynchronization (ERD) to both angry and neutral expressions. The high AQ group displayed greater low beta ERD to angry than to happy expressions. There was also significantly more low beta ERD to happy faces for the low than for the high AQ group. In conclusion, an interesting interaction between AQ group and emotional expression revealed that hMNS activation can be modulated by emotional facial expressions and that this is differentiated according to individual differences in the level of autistic traits. The EEG index of hMNS activation (mu suppression) seems to be a sensitive measure of the variability in facial processing in typically developing individuals with high and low self-reported traits of autism.

Non-ergodicity of inviscid two-dimensional flow on a beta-plane and on the surface of a rotating sphere

It is shown that, for a sufficiently large value of β, two-dimensional flow on a doubly-periodic beta-plane cannot be ergodic (phase-space filling) on the phase-space surface of constant energy and enstrophy. A corresponding result holds for flow on the surface of a rotating sphere, for a sufficiently rapid rotation rate Ω. This implies that the higher-order, non-quadratic invariants are exerting a significant influence on the statistical evolution of the flow. The proof relies on the existence of a finite-amplitude Liapunov stability theorem for zonally symmetric basic states with a non-vanishing absolute-vorticity gradient. When the domain size is much larger than the size of a typical eddy, then a sufficient condition for non-ergodicity is that the wave steepness ε < 1, where ε = 2[surd radical]2Z/βU in the planar case and $\epsilon = 2^{\frac{1}{4}} a^{\frac{5}{2}}Z^{\frac{7}{4}}/\Omega U^{\frac{5}{2}}$ in the spherical case, and where Z is the enstrophy, U the r.m.s. velocity, and a the radius of the sphere. This result may help to explain why numerical simulations of unforced beta-plane turbulence (in which ε decreases in time) seem to evolve into a non-ergodic regime at large scales.

The use of culture-independent tools to characterize bacteria in endo-tracheal aspirates from pre-term infants at risk of bronchopulmonary dysplasia

Although premature infants are increasingly surviving the neonatal period, up to one-third develop bronchopulmonary dysplasia (BPD). Despite evidence that bacterial colonization of the neonatal respiratory tract by certain bacteria may be a risk factor in BPD development, little is known about the role these bacteria play. The aim of this study was to investigate the use of culture-independent molecular profiling methodologies to identify potential etiological agents in neonatal airway secretions. This study used terminal restriction fragment length polymorphism (T-RFLP) and clone sequence analyses to characterize bacterial species in endo-tracheal (ET) aspirates from eight intubated pre-term infants. A wide range of different bacteria was identified in the samples. Forty-seven T-RF band lengths were resolved in the sample set, with a range of 0-15 separate species in each patient. Clone sequence analyses confirmed the identity of individual species detected by T-RFLP. We speculate that the identification of known opportunistic pathogens including S. aureus, Enterobacter sp., Moraxella catarrhalis, Pseudomonas aeruginosa and Streptococcus sp., within the airways of pre-term infants, might be causally related to the subsequent development of BPD. Further, we suggest that culture-independent techniques, such as T-RFLP, hold important potential for the characterization of neonatal conditions, such as BPD.

The growth rate and dimension theory of beta-expansions

In a recent paper of Feng and Sidorov they show that for β∈(1,(1+5√)/2) the set of β-expansions grows exponentially for every x∈(0,1/(β−1)). In this paper we study this growth rate further. We also consider the set of β-expansions from a dimension theory perspective.

Differential crosstalk between estrogen receptor (ER) alpha and ER beta and the thyroid hormone receptor isoforms results in flexible regulation of the consensus ERE

Crosstalk between nuclear receptors is important for conversion of external and internal stimuli to a physiologically meaningful response by cells. Previous studies from this laboratory have demonstrated crosstalk between the estrogen (ER) and thyroid hormone receptors (TR) on two estrogen responsive physiological promoters, the preproenkephalin and oxytocin receptor gene promoter. Since ERa and ERb are isoforms possessing overlapping and distinct transactivation properties, we hypothesized that the interaction of ERa and b with the various TR isoforms would not be equivalent. To explore this hypothesis, the consensus estrogen response element (ERE)derived from the Xenopus vitellogenin gene is used to investigate the differences in interaction between ERa and b isoforms and the different TR isoforms in fibroblast cells. Both the ER isoforms transactivate from the consensus ERE, though ERa transactivates to a greater extent than ERb. Although neither of the TRb isoforms have an effect on ERa transactivation from the consensus ERE, the liganded TRa1 inhibits the ERa transactivation from the consensus ERE. In contrast, the liganded TRa1 facilitates ERb-mediated transactivation. The crosstalk between the TRb isoforms with the ERa isoform, on the consensus ERE, is different from that with the ERb isoform. The use of a TRa1 mutant, which is unable to bind DNA, abolishes the ability of the TRa1 isoform to interact with either of the ER isoforms. These differences in nuclear receptor crosstalk reveal an important functional difference between isoforms, which provides a novel mechanism for neuroendocrine integration.

Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor alpha1 or beta isoforms

Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRalpha and TRbeta. The loss of TRalpha1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRalpha1 knockout (alpha1KO) and TRbeta (betaKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRalpha1 and TRbeta, in the regulation of state anxiety, with alpha1 knockout animals (alpha1KO) showing higher levels of anxiety and betaKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, alpha1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in alpha1KO male mice. These behaviors support the idea that TRalpha1 could be inhibitory to ERalpha driven transcription that ultimately impacts ERalpha driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle.