A six-generation Chinese family in haplogroup B4C1C exhibits high penetrance of 1555A > G-induced hearing Loss

<p>Abstract</p> <p>Background</p> <p>The 1555A > G mutation is the most common cause of aminoglycoside-induced and non-syndromic deafness. However, the variable clinical phenotype and incomplete penetrance of A1555G-induced hearing loss complicate our understanding of this mutation. Environmental factors, nuclear genes, mitochondrial haplotypes/variants and a possible threshold effect have been reported to may be involved in its manifestation.</p> <p>Methods</p> <p>Here, we performed a clinical, molecular, genetic and phylogenic analysis in a six-generation Chinese family.</p> <p>Results</p> <p>A clinical evaluation revealed that affected individuals without aminoglycoside exposure developed hearing loss extending gradually from 12000 Hz to 8000 Hz and then to 4000 Hz. Using pyrosequencing, we detected an identical homoplasmic 1555A > G mutation in all individuals except one. We did not find any correlation between the mutation load and the severity of hearing loss. T123N coexisted with the 1555A > G mutation in six affected subjects in our pedigree. Analysis of the complete mtDNA genome of this family revealed that this family belonged to haplotype B4C1C and exhibited high penetrance. Upon the inclusion of subjects that had been exposed to aminoglycosides, the penetrance of the hearing loss was 63.6%.; without exposure to aminoglycosides, it was 51.5%. This pedigree and another reported Chinese pedigree share the same haplotype (B4C1C) and lack functionally significant mitochondrial tRNA variants, but nevertheless they exhibit a different penetrance of hearing loss.</p> <p>Conclusions</p> <p>Our results imply that the factors responsible for the higher penetrance and variable expression of the deafness associated with the 1555A > G mutation in this pedigree may not be mtDNA haplotype/variants, but rather nuclear genes and/or aminoglycosides.</p

State Control and the Effects of Foreign Relations on Bilateral Trade

Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy

Effects of thickness and interlayer on optical properties of AlN films at room and high temperature

This paper investigates the systematic influence of thickness (136-412 nm) and temperature (300-860 K) on the refractive index and the band-edge of aluminum nitride (AlN) films. The combination of x-ray diffraction, spectroscopic ellipsometry (SE), and transmittance measurements at 300 K shows that the increase of epilayer thickness or the introduction of an AlN interlayer can improve the crystal quality. This is observed as an enlargement of the grain size, a reduction of the Urbach binding energy, and strain with a corresponding increase in the refractive index and bandgap. Moreover, the expected reduction in the bandgap and the increase of the refractive index are observed at elevated temperatures by SE. The temperature dependence of the refractive index at 632.8 nm and the bandgap were well understood and modeled using a quadratic nonlinear equation and the Bose-Einstein equation, respectively. This high-temperature phenomenological and quantitative analysis suggests that the reduction of the bandgap with temperature is more significant in thinner or noninterlayer films than expected due to the corresponding stronger electron-phonon interactions involved with larger Urbach binding energies. The thickest AlN film in this work (with an epilayer thickness of 412.9 nm and an interlayer thickness of 20.69 nm) has the smallest strength of the average electron-phonon coupling (407 meV) in the temperature range 300-860 K. On the other hand, the temperature-dependent variation of the refractive index in the transparent region is more rapid as the film thickness decreases owing to the high correlation between temperature-dependent bandgap and refractive index. These observations are critical when designing AlN-based device structures that can operate well above room temperature

Effects of thickness and interlayer on optical properties of AlN films at room and high temperature

This paper investigates the systematic influence of thickness (136-412 nm) and temperature (300-860 K) on the refractive index and the band-edge of aluminum nitride (AlN) films. The combination of x-ray diffraction, spectroscopic ellipsometry (SE), and transmittance measurements at 300 K shows that the increase of epilayer thickness or the introduction of an AlN interlayer can improve the crystal quality. This is observed as an enlargement of the grain size, a reduction of the Urbach binding energy, and strain with a corresponding increase in the refractive index and bandgap. Moreover, the expected reduction in the bandgap and the increase of the refractive index are observed at elevated temperatures by SE. The temperature dependence of the refractive index at 632.8 nm and the bandgap were well understood and modeled using a quadratic nonlinear equation and the Bose-Einstein equation, respectively. This high-temperature phenomenological and quantitative analysis suggests that the reduction of the bandgap with temperature is more significant in thinner or noninterlayer films than expected due to the corresponding stronger electron-phonon interactions involved with larger Urbach binding energies. The thickest AlN film in this work (with an epilayer thickness of 412.9 nm and an interlayer thickness of 20.69 nm) has the smallest strength of the average electron-phonon coupling (407 meV) in the temperature range 300-860 K. On the other hand, the temperature-dependent variation of the refractive index in the transparent region is more rapid as the film thickness decreases owing to the high correlation between temperature-dependent bandgap and refractive index. These observations are critical when designing AlN-based device structures that can operate well above room temperature

New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis

Pharyngeal shedding of challenge strain and chlamydial loads in lungs after challenge.

<p>The number of chlamydial inclusions in each group (<i>n</i> = 10 for CEF control group and parental HVT group, <i>n</i> = 15 for rHVT-<i>pmpD</i>-N group) was counted in five randomly selected microscopic fields as described in M&M section. The values were shown as dot plots and medians. (A) Median score of pharyngeal shedding of <i>C</i>. <i>psittaci</i> CB7 strain. (B) Chlamydial loads in lungs after challenge. ^a–bBars in the lungs or pharyngeal swabs with the different superscripts are significantly different.</p

Antigen-specific proliferation responses.

<p>PBLs (<i>n</i> = 5 for each group) were obtained from immunized chickens on days 35, and lymphocytes were stimulated with 400 PFU of inactivated rHVT-<i>pmpD</i>-N. The results were examined as the stimulation index, calculated as the mean counts per minute (cpm) values of stimulated and non-stimulated wells. The values were shown as dot plots and means. ^a–cBars with the different superscripts indicate statistically significant difference among three groups.</p