Modified protein expression in the tectorial membrane of the cochlea reveals roles for the striated sheet matrix

The tectorial membrane (TM) of the mammalian cochlea is a complex extracellular matrix which, in response to acoustic stimulation, displaces the hair bundles of outer hair cells (OHCs), thereby initiating sensory transduction and amplification. Here, using TM segments from the basal, high-frequency region of the cochleae of genetically modified mice (including models of human hereditary deafness) with missing or modified TM proteins, we demonstrate that frequency-dependent stiffening is associated with the striated sheet matrix (SSM). Frequency-dependent stiffening largely disappeared in all three TM mutations studied where the SSM was absent either entirely or at least from the stiffest part of the TM overlying the OHCs. In all three TM mutations, dissipation of energy is decreased at low (<8 kHz) and increased at high (>8 kHz) stimulus frequencies. The SSM is composed of polypeptides carrying fixed charges, and electrostatic interaction between them may account for frequency-dependent stiffness changes in the material properties of the TM. Through comparison with previous in vivo measurements, it is proposed that implementation of frequency-dependent stiffening of the TM in the OHC attachment region facilitates interaction among tones, backward transmission of energy, and amplification in the cochlea

Synchronization of a Nonlinear Oscillator: Processing the Cf Component of the Echo-Response Signal in the Cochlea of the Mustached Bat

Cochlear microphonic potential (CM) was recorded from the CF2 region and the sparsely innervated zone (the mustached bat's cochlea fovea) that is specialized for analyzing the Doppler-shifted echoes of the first-harmonic (~61 kHz) of the constant-frequency component of the echolocation call. Temporal analysis of the CM, which is tuned sharply to the 61 kHz cochlear resonance, revealed that at the resonance frequency, and within 1 msec of tone onset, CM is broadly tuned with linear magnitude level functions. CM measured during the ongoing tone and in the ringing after tone offset is 50 dB more sensitive, is sharply tuned, has compressive level functions, and the phase leads onset CM by 90°: an indication that cochlear responses are amplified during maximum basilar membrane velocity. For high-level tones above the resonance frequency, CM appears at tone onset and after tone offset. Measurements indicate that the two oscillators responsible for the cochlear resonance, presumably the basilar and tectorial membranes, move together in phase during the ongoing tone, thereby minimizing net shear between them and hair cell excitation. For tones within 2 kHz of the cochlear resonance the frequency of CM measured within 2 msec of tone onset is not that of the stimulus but is proportional to it. For tones just below the cochlear resonance region CM frequency is a constant amount below that of the stimulus depending on CM measurement delay from tone onset. The frequency responses of the CM recorded from the cochlear fovea can be accounted for through synchronization between the nonlinear oscillators responsible for the cochlear resonance and the stimulus tone

Volatile hydrocarbons inhibit methanogenic crude oil degradation

Methanogenic degradation of crude oil in subsurface sediments occurs slowly, but without the need for exogenous electron acceptors, is sustained for long periods and has enormous economic and environmental consequences. Here we show that volatile hydrocarbons are inhibitory to methanogenic oil biodegradation by comparing degradation of an artificially weathered crude oil with volatile hydrocarbons removed, with the same oil that was not weathered. Volatile hydrocarbons (nC5-nC10, methylcyclohexane, benzene, toluene, and xylenes) were quantified in the headspace of microcosms. Aliphatic (n-alkanes nC12-nC34) and aromatic hydrocarbons (4-methylbiphenyl, 3-methylbiphenyl, 2-methylnaphthalene, 1-methylnaphthalene) were quantified in the total hydrocarbon fraction extracted from the microcosms. 16S rRNA genes from key microorganisms known to play an important role in methanogenic alkane degradation (Smithella and Methanomicrobiales) were quantified by quantitative PCR. Methane production from degradation of weathered oil in microcosms was rapid (1.1 ± 0.1 μmol CH4/g sediment/day) with stoichiometric yields consistent with degradation of heavier n-alkanes (nC12-nC34). For non-weathered oil, degradation rates in microcosms were significantly lower (0.4 ± 0.3 μmol CH4/g sediment/day). This indicated that volatile hydrocarbons present in the non-weathered oil inhibit, but do not completely halt, methanogenic alkane biodegradation. These findings are significant with respect to rates of biodegradation of crude oils with abundant volatile hydrocarbons in anoxic, sulphate-depleted subsurface environments, such as contaminated marine sediments which have been entrained below the sulfate-reduction zone, as well as crude oil biodegradation in petroleum reservoirs and contaminated aquifers

Mindfulness-Based Cognitive Therapy: Further Issues in Current Evidence and Future Research

The authors respond to the article by H. F. Coelho, P. H. Canter, and E. Ernst (2007)A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) after treatment

Systematic review of topical treatments for fungal infections of the skin and nails of the feet

OBJECTIVE: To identify and synthesise the evidence for efficacy and cost effectiveness of topical treatments for superficial fungal infections of the skin and nails of the feet. DESIGN: Systematic review. INTERVENTIONS: Topical treatments for superficial fungal infections. MAIN OUTCOME MEASURES: Cure confirmed by culture and microscopy for skin and by culture for nails in patients with clinically diagnosed fungal infections. RESULTS: Of 126 trials identified in 121 papers, 72 (57.1%) met the inclusion criteria. Placebo controlled trials yielded pooled relative risks of failure to cure skin infections: allylamines (0.30, 95% confidence interval 0.24 to 0.38); azoles (0.54, 0.42 to 0.68); undecenoic acid (0.28, 0.11 to 0.74); and tolnaftate (0.46, 0.17 to 1.22). Although meta-analysis of 11 trials comparing allylamines and azoles showed a relative risk of failure to cure of 0.88 (0.78 to 0.99) in favour of allylamines, there was evidence of language bias. Seven reports in English favoured allylamines (0.79, 0.69 to 0.91), but four reports in foreign languages showed no difference between the two drugs (1.01, 0.90 to 1.13). Neither trial of nail infections showed significant differences between alternative topical treatments. CONCLUSIONS: Allylamines, azoles, and undecenoic acid were efficacious in placebo controlled trials. There are sufficient comparative trials to judge relative efficacy only between allylamines and azoles. Allylamines cure slightly more infections than azoles but are much more expensive than azoles. The most cost effective strategy is first to treat with azoles or undecenoic acid and to use allylamines only if that fails

A phase field method for tomographic reconstruction from limited data.

Classical tomographic reconstruction methods fail for problems in which there is extreme temporal and spatial sparsity in the measured data. Reconstruction of coronal mass ejections (CMEs), a space weather phenomenon with potential negative effects on the Earth, is one such problem. However, the topological complexity of CMEs renders recent limited data reconstruction methods inapplicable. We propose an energy function, based on a phase field level set framework, for the joint segmentation and tomographic reconstruction of CMEs from measurements acquired by coronagraphs, a type of solar telescope. Our phase field model deals easily with complex topologies, and is more robust than classical methods when the data are very sparse. We use a fast variational algorithm that combines the finite element method with a trust region variant of Newton’s method to minimize the energy. We compare the results obtained with our model to classical regularized tomography for synthetic CME-like images

Affective commitment within the public sector: Antecedents and performance outcomes between ownership types

How to generate affective commitment and realize its performance potential is deemed critical to public management. But in the context of service outsourcing, does ownership type influence its antecedents and performance outcomes? Drawing on postal survey data for English leisure providers, we find training is an antecedent across public and private ownership types; performance appraisal is an antecedent for private ownership only; while performance-related pay carries an insignificant effect. Affective commitment holds business and customer performance outcomes for public ownership, but insignificant effects are observed for external ownership types. Implications of this contextual variation for public management theory are discussed

Is arterial stiffening associated with adiposity, severity of obesity and other contemporary cardiometabolic markers in a community sample of adolescents with obesity in the UK?

BACKGROUND: Cardiovascular disease (CVD) prediction is problematic within groups of obese adolescents as measures such as adiposity and metabolic markers lack validation. Pulse wave velocity (PWV), a proxy for arterial stiffening, is a potential way to contemporaneously capture adolescents at greater risk of CVD. OBJECTIVES: To investigate associations between PWV and 1) adiposity and 2) other conventional metabolic factors in a community sample of (>95th centile body mass index (BMI)). DESIGN AND SETTING: Cross-sectional measurement and analysis in a hospital-based research centre drawn from a community sample of adolescents recruited to an obesity intervention at baseline. PATIENTS: 174 adolescents (12-19 years) with obesity (>95th centile BMI). 37% were male, while 66 (38%) were white, 53 (30%) black, 36 (21%) South Asian, 19 (11%) mixed/other. Participants with endocrine, genetic causes of obesity and chronic medical conditions (excluding asthma) were excluded. MEASURES: BMI z-score (zBMI), waist z-score, fat mass index (FMI: measured using bioimpedance), sagittal abdominal dimension (SAD), cardiometabolic blood tests and resting blood pressure (BP) were collected. Carotid-radial PWV was measured by a single operator. RESULTS: PWV was associated with age but not pubertal stage. PWV was positively associated with adiposity (zBMI: coefficient 0.44 (95% CI 0.08 to 0.79); FMI: coefficient 0.05 (95% CI 0.00 to 0.10); waist z-score: coefficient 0.27 (95% CI 0.00 to 0.53); SAD: coefficient 0.06 (95% CI: 0.00 to 0.12)). There was no association between PWV and BP, and few associations with cardiometabolic bloods. Associations between PWV and adiposity measures were robust to adjustment in multivariable models except for SAD. Participants with zBMI >2.5 SD and >3.5 SD had greater average PWV but overlap between groups was large. CONCLUSIONS: In our sample, increasing adiposity was positively associated with arterial stiffness, however partitioning by severity was not reliable. Lack of associations between BP, cardiometabolic bloods and arterial stiffness questions the reliability of these factors for predicting CVD risk in adolescents with obesity

MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1

Congenital heart defects are the most common birth defects in humans, and those that affect the proper alignment of the outflow tracts and septation of the ventricles are a highly significant cause of morbidity and mortality in infants. A late differentiating population of cardiac progenitors, referred to as the anterior second heart field (AHF), gives rise to the outflow tract and the majority of the right ventricle and provides an embryological context for understanding cardiac outflow tract alignment and membranous ventricular septal defects. However, the transcriptional pathways controlling AHF development and their roles in congenital heart defects remain incompletely elucidated. Here, we inactivated the gene encoding the transcription factor MEF2C in the AHF in mice. Loss of Mef2c function in the AHF results in a spectrum of outflow tract alignment defects ranging from overriding aorta to double-outlet right ventricle and dextro-transposition of the great arteries. We identify Tdgf1, which encodes a Nodal co-receptor (also known as Cripto), as a direct transcriptional target of MEF2C in the outflow tract via an AHFrestricted Tdgf1 enhancer. Importantly, both the MEF2C and TDGF1 genes are associated with congenital heart defects in humans. Thus, these studies establish a direct transcriptional pathway between the core cardiac transcription factor MEF2C and the human congenital heart disease gene TDGF1. Moreover, we found a range of outflow tract alignment defects resulting from a single genetic lesion, supporting the idea that AHF-derived outflow tract alignment defects may constitute an embryological spectrum rather than distinct anomalies