Differences in hearing acuity among “normal-hearing” young adults modulate the neural basis for speech comprehension

AbstractIn this paper, we investigate how subtle differences in hearing acuity affect the neural systems supporting speech processing in young adults. Auditory sentence comprehension requires perceiving a complex acoustic signal and performing linguistic operations to extract the correct meaning. We used functional MRI to monitor human brain activity while adults aged 18–41 years listened to spoken sentences. The sentences varied in their level of syntactic processing demands, containing either a subject-relative or object-relative center-embedded clause. All participants self-reported normal hearing, confirmed by audiometric testing, with some variation within a clinically normal range. We found that participants showed activity related to sentence processing in a left-lateralized frontotemporal network. Although accuracy was generally high, participants still made some errors, which were associated with increased activity in bilateral cingulo-opercular and frontoparietal attention networks. A whole-brain regression analysis revealed that activity in a right anterior middle frontal gyrus (aMFG) component of the frontoparietal attention network was related to individual differences in hearing acuity, such that listeners with poorer hearing showed greater recruitment of this region when successfully understanding a sentence. The activity in right aMFGs for listeners with poor hearing did not differ as a function of sentence type, suggesting a general mechanism that is independent of linguistic processing demands. Our results suggest that even modest variations in hearing ability impact the systems supporting auditory speech comprehension, and that auditory sentence comprehension entails the coordination of a left perisylvian network that is sensitive to linguistic variation with an executive attention network that responds to acoustic challenge.</jats:p

How does human motor cortex regulate vocal pitch in singers?

Vocal pitch is used as an important communicative device by humans, as found in the melodic dimension of both speech and song. Vocal pitch is determined by the degree of tension in the vocal folds of the larynx, which itself is influenced by complex and nonlinear interactions among the laryngeal muscles. The relationship between these muscles and vocal pitch has been described by a mathematical model in the form of a set of ‘control rules’. We searched for the biological implementation of these control rules in the larynx motor cortex of the human brain. We scanned choral singers with functional magnetic resonance imaging as they produced discrete pitches at four different levels across their vocal range. While the locations of the larynx motor activations varied across singers, the activation peaks for the four pitch levels were highly consistent within each individual singer. This result was corroborated using multi-voxel pattern analysis, which demonstrated an absence of patterned activations differentiating any pairing of pitch levels. The complex and nonlinear relationships between the multiple laryngeal muscles that control vocal pitch may obscure the neural encoding of vocal pitch in the brain

Review of the mechanisms of debris-flow impact against barriers

Our limited understanding of the mechanisms pertaining to the force exerted by debris flows on barriers makes it difficult to ascertain whether a design is inadequate, adequate, or over-designed. The main scientific challenge is because flow-type landslides impacting a rigid barrier is rarely captured in the field, and no systematic, physical experimental data is available to reveal the impact mechanisms. An important consideration in flow-structure interaction is that the impact dynamics can differ radically depending on the composition of the flow. Currently, no framework exists that can characterize the impact behavior for a wide range of flow compositions. This review paper examines recent works on debris-flow structure interactions and the limitations of commonly used approaches to estimate the impact load for the design of barriers. Key challenges faced in this area and outlook for further research are discussed

Performance evaluation of IB-DFE-based strategies for SC-FDMA systems

The aim of this paper is to propose and evaluate multi-user iterative block decision feedback equalization (IB-DFE) schemes for the uplink of single-carrier frequency-division multiple access (SC-FDMA)-based systems. It is assumed that a set of single antenna users share the same physical channel to transmit its own information to the base station, which is equipped with an antenna array. Two space-frequency multi-user IB-DFE-based processing are considered: iterative successive interference cancellation and parallel interference cancellation. In the first approach, the equalizer vectors are computed by minimizing the mean square error (MSE) of each individual user, at each subcarrier. In the second one, the equalizer matrices are obtained by minimizing the overall MSE of all users at each subcarrier. For both cases, we propose a simple yet accurate analytical approach for obtaining the performance of the discussed receivers. The proposed schemes allow an efficient user separation, with a performance close to the one given by the matched filter bound for severely time-dispersive channels, with only a few iterations

Tolerogenic Function of Dimeric Forms of HLA-G Recombinant Proteins: A Comparative Study In Vivo

HLA-G is a natural tolerogenic molecule involved in the best example of tolerance to foreign tissues there is: the maternal-fetal tolerance. The further involvement of HLA-G in the tolerance of allogeneic transplants has also been demonstrated and some of its mechanisms of action have been elucidated. For these reasons, therapeutic HLA-G molecules for tolerance induction in transplantation are actively investigated. In the present study, we studied the tolerogenic functions of three different HLA-G recombinant proteins: HLA-G heavy chain fused to β2-microglobulin (B2M), HLA-G heavy chain fused to B2M and to the Fc portion of an immunoglobulin, and HLA-G alpha-1 domain either fused to the Fc part of an immunoglobulin or as a synthetic peptide. Our results demonstrate the tolerogenic function of B2M-HLA-G fusion proteins, and especially of B2M-HLA-G5, which were capable of significantly delaying allogeneic skin graft rejection in a murine in vivo transplantation model. The results from our studies suggest that HLA-G recombinant proteins are relevant candidates for tolerance induction in human transplantation

Activated Microglia Inhibit Axonal Growth through RGMa

By causing damage to neural networks, spinal cord injuries (SCI) often result in severe motor and sensory dysfunction. Functional recovery requires axonal regrowth and regeneration of neural network, processes that are quite limited in the adult central nervous system (CNS). Previous work has shown that SCI lesions contain an accumulation of activated microglia, which can have multiple pathophysiological influences. Here, we show that activated microglia inhibit axonal growth via repulsive guidance molecule a (RGMa). We found that microglia activated by lipopolysaccharide (LPS) inhibited neurite outgrowth and induced growth cone collapse of cortical neurons in vitro—a pattern that was only observed when there was direct contact between microglia and neurons. After microglia were activated by LPS, they increased expression of RGMa; however, treatment with RGMa-neutralizing antibodies or transfection of RGMa siRNA attenuated the inhibitory effects of microglia on axonal outgrowth. Furthermore, minocycline, an inhibitor of microglial activation, attenuated the effects of microglia and RGMa expression. Finally, we examined whether these in vitro patterns could also be observed in vivo. Indeed, in a mouse SCI model, minocycline treatment reduced the accumulation of microglia and decreased RGMa expression after SCI, leading to reduced dieback in injured corticospinal tracts. These results suggest that activated microglia play a major role in inhibiting axon regeneration via RGMa in the injured CNS

Multimeric structures of HLA-G isoforms function through differential binding to LILRB receptors

The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α(1)-α(2)-α(3) non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α(1)-α(3) structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α(1)-α(3)-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents

Analysis of antimicrobial susceptibility and virulence factors in Helicobacter pylori clinical isolates

BACKGROUND: In this study, we evaluated the prevalence of primary resistance of Brazilian H. pylori isolates to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone. In addition, the vacA, iceA, cagA and cagE genotypes of strains isolated from Brazilian patients were determined and associated with clinical data in an effort to correlate these four virulence markers and antibiotic resistance. METHODS: H. pylori was cultured in 155 H. pylori-positive patients and MICs for metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone were determined by the agar dilution method. Genomic DNA was extracted, and allelic variants of vacA, iceA, cagA and cagE were identified by the polymerase chain reaction. RESULTS: There was a strong association between the vacA s1/cagA -positive genotype and peptic ulcer disease (OR = 5.42, 95% CI 2.6–11.3, p = 0.0006). Additionally, infection by more virulent strains may protect against GERD, since logistic regression showed a negative association between the more virulent strain, vacA s1/cagA-positive genotype and GERD (OR = 0.26, 95% CI 0.08–0.8, p = 0.03). Resistance to metronidazole was detected in 75 patients (55%), to amoxicillin in 54 individuals (38%), to clarithromycin in 23 patients (16%), to tetracycline in 13 patients (9%), and to furazolidone in 19 individuals (13%). No significant correlation between pathogenicity and resistance or susceptibility was detected when MIC values for each antibiotic were compared with different vacA, iceA, cagA and cagE genotypes. CONCLUSION: The analysis of virulence genes revealed a specific association between H. pylori strains and clinical outcome, furthermore, no significant association was detected among pathogenicity and resistance or susceptibility

Inflammogenesis of Secondary Spinal Cord Injury

Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine.Grant #NPRP 4-571-3-171 from the Qatar National Research Fund(a member of Qatar Foundation)