The p.V37I Exclusive Genotype Of GJB2: A Genetic Risk-Indicator of Postnatal Permanent Childhood Hearing Impairment

Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%–0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10−10; OR 62.92, 95% CI 21.27–186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI

Inhibition of the Mitochondrial Enzyme ABAD Restores the Amyloid-β-Mediated Deregulation of Estradiol

Alzheimer's disease (AD) is a conformational disease that is characterized by amyloid-β (Aβ) deposition in the brain. Aβ exerts its toxicity in part by receptor-mediated interactions that cause down-stream protein misfolding and aggregation, as well as mitochondrial dysfunction. Recent reports indicate that Aβ may also interact directly with intracellular proteins such as the mitochondrial enzyme ABAD (Aβ binding alcohol dehydrogenase) in executing its toxic effects. Mitochondrial dysfunction occurs early in AD, and Aβ's toxicity is in part mediated by inhibition of ABAD as shown previously with an ABAD decoy peptide. Here, we employed AG18051, a novel small ABAD-specific compound inhibitor, to investigate the role of ABAD in Aβ toxicity. Using SH-SY5Y neuroblastoma cells, we found that AG18051 partially blocked the Aβ-ABAD interaction in a pull-down assay while it also prevented the Aβ42-induced down-regulation of ABAD activity, as measured by levels of estradiol, a known hormone and product of ABAD activity. Furthermore, AG18051 is protective against Aβ42 toxicity, as measured by LDH release and MTT absorbance. Specifically, AG18051 reduced Aβ42-induced impairment of mitochondrial respiration and oxidative stress as shown by reduced ROS (reactive oxygen species) levels. Guided by our previous finding of shared aspects of the toxicity of Aβ and human amylin (HA), with the latter forming aggregates in Type 2 diabetes mellitus (T2DM) pancreas, we determined whether AG18051 would also confer protection from HA toxicity. We found that the inhibitor conferred only partial protection from HA toxicity indicating distinct pathomechanisms of the two amyloidogenic agents. Taken together, our results present the inhibition of ABAD by compounds such as AG18051 as a promising therapeutic strategy for the prevention and treatment of AD, and suggest levels of estradiol as a suitable read-out

All-Optical Generation of Surface Plasmons in Graphene

27 pages, 12 figures, includes supplementary materialarXiv is an e-print service in the fields of physics, mathematics, computer science, quantitative biology, quantitative finance and statistics.Here we present an all-optical plasmon coupling scheme, utilising the intrinsic nonlinear optical response of graphene. We demonstrate coupling of free-space, visible light pulses to the surface plasmons in a planar, un-patterned graphene sheet by using nonlinear wave mixing to match both the wavevector and energy of the surface wave. By carefully controlling the phase-matching conditions, we show that one can excite surface plasmons with a defined wavevector and direction across a large frequency range, with an estimated photon efficiency in our experiments approaching $10^{-5}$

Clinical management of gastric cancer: results of a multicentre survey

<p>Abstract</p> <p>Background</p> <p>The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines.</p> <p>Methods</p> <p>A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer.</p> <p>Results</p> <p>Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines.</p> <p>Conclusions</p> <p>These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines.</p

Consumption of a soy drink has no effect on cognitive function but may alleviate vasomotor symptoms in post-menopausal women; a randomised trial

Purpose: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. Methods: 101 post-menopausal women, aged 44–63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene’s Climacteric Scale. Results: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: − 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). Conclusions: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women

Adverse Effect of Nano-Silicon Dioxide on Lung Function of Rats with or without Ovalbumin Immunization

BACKGROUND: The great advances of nanomaterials have brought out broad important applications, but their possible nanotoxicity and risks have not been fully understood. It is confirmed that exposure of environmental particulate matter (PM), especially ultrafine PM, are responsible for many lung function impairment and exacerbation of pre-existing lung diseases. However, the adverse effect of nanoparticles on allergic asthma is seldom investigated and the mechanism remains undefined. For the first time, this work investigates the relationship between allergic asthma and nanosized silicon dioxide (nano-SiO₂). METHODOLOGY/PRINCIPAL FINDINGS: Ovalbumin (OVA)-treated and saline-treated control rats were daily intratracheally administered 0.1 ml of 0, 40 and 80 µg/ml nano-SiO₂ solutions, respectively for 30 days. Increased nano-SiO₂ exposure results in adverse changes on inspiratory and expiratory resistance (Ri and Re), but shows insignificant effect on rat lung dynamic compliance (Cldyn). Lung histological observation reveals obvious airway remodeling in 80 µg/ml nano-SiO₂-introduced saline and OVA groups, but the latter is worse. Additionally, increased nano-SiO₂ exposure also leads to more severe inflammation. With increasing nano-SiO₂ exposure, IL-4 in lung homogenate increases and IFN-γ shows a reverse but insignificant change. Moreover, at a same nano-SiO₂ exposure concentration, OVA-treated rats exhibit higher (significant) IL-4 and lower (not significant) IFN-γ compared with the saline-treated rats. The percentages of eosinophil display an unexpected result, in which higher exposure results lower eosinophil percentages. CONCLUSIONS/SIGNIFICANCE: This was a preliminary study which for the first time involved the effect of nano-SiO₂ to OVA induced rat asthma model. The results suggested that intratracheal administration of nano-SiO₂ could lead to the airway hyperresponsiveness (AHR) and the airway remolding with or without OVA immunization. This occurrence may be due to the Th1/Th2 cytokine imbalance accelerated by the nano-SiO₂ through increasing the tissue IL-4 production

Id1 Interacts and Stabilizes the Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) in Nasopharyngeal Epithelial Cells

The EBV-encoded latent membrane protein 1 (LMP1) functions as a constitutive active form of tumor necrosis factor receptor (TNFR) and activates multiple downstream signaling pathways similar to CD40 signaling in a ligand-independent manner. LMP1 expression in EBV-infected cells has been postulated to play an important role in pathogenesis of nasopharyngeal carcinoma. However, variable levels of LMP1 expression were detected in nasopharyngeal carcinoma. At present, the regulation of LMP1 levels in nasopharyngeal carcinoma is poorly understood. Here we show that LMP1 mRNAs are transcribed in an EBV-positive nasopharyngeal carcinoma (NPC) cell line (C666-1) and other EBV-negative nasopharyngeal carcinoma cells stably re-infected with EBV. The protein levels of LMP1 could readily be detected after incubation with proteasome inhibitor, MG132 suggesting that LMP1 protein is rapidly degraded via proteasome-mediated proteolysis. Interestingly, we observed that Id1 overexpression could stabilize LMP1 protein in EBV-infected cells. In contrary, Id1 knockdown significantly reduced LMP1 levels in cells. Co-immunoprecipitation studies revealed that Id1 interacts with LMP1 by binding to the CTAR1 domain of LMP1. N-terminal region of Id1 is required for the interaction with LMP1. Furthermore, binding of Id1 to LMP1 suppressed polyubiquitination of LMP1 and may be involved in stabilization of LMP1 in EBV-infected nasopharyngeal epithelial cells

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded

The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: a nested case-control study in the California Teachers Study cohort

Abstract Introduction The female sex steroids estrogen and progesterone are important in breast cancer etiology. It therefore seems plausible that variation in genes involved in metabolism of these hormones may affect breast cancer risk, and that these associations may vary depending on menopausal status and use of hormone therapy. Methods We conducted a nested case-control study of breast cancer in the California Teachers Study cohort. We analyzed 317 tagging single nucleotide polymorphisms (SNPs) in 24 hormone pathway genes in 2746 non-Hispanic white women: 1351 cases and 1395 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by fitting conditional logistic regression models using all women or subgroups of women defined by menopausal status and hormone therapy use. P values were adjusted for multiple correlated tests (P ACT). Results The strongest associations were observed for SNPs in SLCO1B1, a solute carrier organic anion transporter gene, which transports estradiol-17β-glucuronide and estrone-3-sulfate from the blood into hepatocytes. Ten of 38 tagging SNPs of SLCO1B1 showed significant associations with postmenopausal breast cancer risk; 5 SNPs (rs11045777, rs11045773, rs16923519, rs4149057, rs11045884) remained statistically significant after adjusting for multiple testing within this gene (P ACT = 0.019-0.046). In postmenopausal women who were using combined estrogen-progestin therapy (EPT) at cohort enrollment, the OR of breast cancer was 2.31 (95% CI = 1.47-3.62) per minor allele of rs4149013 in SLCO1B1 (P = 0.0003; within-gene P ACT = 0.002; overall P ACT = 0.023). SNPs in other hormone pathway genes evaluated in this study were not associated with breast cancer risk in premenopausal or postmenopausal women. Conclusions We found evidence that genetic variation in SLCO1B1 is associated with breast cancer risk in postmenopausal women, particularly among those using EPT