bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient auditory nerve demyelination as a new mechanism for hidden hearing loss
Authors: Wan Guoqiang , Corfas Gabriel 
Published: February 2017

AbstractHidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests. Animals and humans with HHL have normal auditory thresholds but defective cochlear neurotransmission, that is, reduced suprathreshold amplitude of the sound-evoked auditory nerve compound action potential. Currently, the only cellular mechanism known for HHL is loss of inner hair cell synapses (synaptopathy). Here we report that transient loss of cochlear Schwann cells results in permanent auditory deficits characteristic of HHL. This auditory neuropathy is not associated with synaptic loss, but rather with disruption of the first heminodes at the auditory nerve peripheral terminal. Thus, this study identifies a new mechanism for HHL, highlights the long-term consequences of transient Schwann cell loss on hearing and might provide insights into the causes of the auditory deficits reported in patients that recover from acute demyelinating diseases such as Guillain–Barré syndrome.
Decoupling absorption and emission processes in super-resolution localization of emitters in a plasmonic hotspot
Authors: Mack David L. , Cortés Emiliano , Giannini Vincenzo , Török Peter , Roschuk Tyler , Maier Stefan A. 
Published: February 2017

AbstractThe absorption process of an emitter close to a plasmonic antenna is enhanced due to strong local electromagnetic (EM) fields. The emission, if resonant with the plasmonic system, re-radiates to the far-field by coupling with the antenna via plasmonic states, whose presence increases the local density of states. Far-field collection of the emission of single molecules close to plasmonic antennas, therefore, provides mixed information of both the local EM field strength and the local density of states. Moreover, super-resolution localizations from these emission-coupled events do not report the real position of the molecules. Here we propose using a fluorescent molecule with a large Stokes shift in order to spectrally decouple the emission from the plasmonic system, leaving the absorption strongly resonant with the antenna’s enhanced EM fields. We demonstrate that this technique provides an effective way of mapping the EM field or the local density of states with nanometre spatial resolution.
Edge currents shunt the insulating bulk in gapped graphene
Authors: Zhu M. J. , Kretinin A. V. , Thompson M. D. , Bandurin D. A. , Hu S. , Yu G. L. , Birkbeck J. , Mishchenko A. , Vera-Marun I. J. , Watanabe K. , Taniguchi T. , Polini M. , Prance J. R. , Novoselov K. S. , Geim A. K. , Ben Shalom M. 
Published: February 2017

AbstractAn energy gap can be opened in the spectrum of graphene reaching values as large as 0.2 eV in the case of bilayers. However, such gaps rarely lead to the highly insulating state expected at low temperatures. This long-standing puzzle is usually explained by charge inhomogeneity. Here we revisit the issue by investigating proximity-induced superconductivity in gapped graphene and comparing normal-state measurements in the Hall bar and Corbino geometries. We find that the supercurrent at the charge neutrality point in gapped graphene propagates along narrow channels near the edges. This observation is corroborated by using the edgeless Corbino geometry in which case resistivity at the neutrality point increases exponentially with increasing the gap, as expected for an ordinary semiconductor. In contrast, resistivity in the Hall bar geometry saturates to values of about a few resistance quanta. We attribute the metallic-like edge conductance to a nontrivial topology of gapped Dirac spectra.
Constitutional variants are not associated with HER2-positive breast cancer: results from the SIGNAL/PHARE clinical cohort
Authors: Pivot Xavier , Romieu Gilles , Fumoleau Pierre , Rios Maria , Bonnefoi Hervé , Bachelot Thomas , Soulié Patrick , Jouannaud Christelle , Bourgeois Hugues , Petit Thierry , Tennevet Isabelle , Assouline David , Mathieu Marie-Christine , Jacquin Jean-Philippe , Lavau-Denes Sandrine , Darut-Jouve Ariane , Ferrero Jean-Marc , Tarpin Carole , Lévy Christelle , Delecroix Valérie , Trillet-Lenoir Véronique , Cojocarasu Oana , Meunier Jérôme , Pierga Jean-Yves , Agostini Cécile , Kerbrat Pierre , Faure-Mercier Céline , Blanché Hélène , Sahbatou Mourad , Boland Anne , Bacq Delphine , Besse Céline , Calvo Fabien , Renaud Alexia , Deleuze Jean-François , Pauporté Iris , Thomas Gilles , Cox David G. 
Published: February 2017

AbstractHuman epidermal growth factor receptor 2-positive breast cancer is a subtype of interest regarding its outcome and the impressive impact of human epidermal growth factor receptor 2 targeted therapy. Constitutional variants may be involved in the aetiology of human epidermal growth factor receptor 2-positive breast cancer, and we propose a case–case study to test the hypothesis that single nucleotide polymorphisms may be associated with human epidermal growth factor receptor 2 status. A Genome-Wide Association Study was used in a cohort of 9836 patients from the SIGNAL/PHARE study (NCT00381901-RECF1098). The main goal was to identify variants specifically related to human epidermal growth factor receptor 2-positive breast cancer. A two-staged genotyping strategy was carried out to cover as large a proportion of the genome as possible. All subjects were genotyped using the Illumina HumanCore Exome chip set. Principal Components Analysis andk-means were then used to characterize the ancestry of the participants. A random sample of subjects from the main “European” cluster was genotyped with the Omni5 chip set. These data were then used to impute missing genotypes from the remaining subjects genotyped only using the HumanCore Exome array. From the 9836 patients, a total of 8703 cases including 3230 patients with human epidermal growth factor receptor 2-positive breast cancer were analyzed. Despite having 80% power to detect an odds ratio of 1.23 in this population, no variant achieved genome-wide significance for association with the occurrence of human epidermal growth factor receptor 2–positive breast cancer vs. any other subtype of breast tumour. Our study was unable to identify constitutional polymorphisms that are strongly associated with human epidermal growth factor receptor 2-positive status among breast cancer patients.
Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells
Authors: Lu Fangjia , Mosley Yung-Yi C. , Rodriguez Rosales Randol J. , Carmichael Brooke E. , Elesela Srikanth , Yao Yuan , HogenEsch Harm 
Published: February 2017

AbstractBiodegradable nanoparticles with functionalized surfaces are attractive candidates as vaccine adjuvants. Nano-11 are cationic dendrimer-like α-D-glucan nanoparticles with a diameter of 70–80 nm. Mice injected with antigen formulated with Nano-11 developed antibody titers that were similar or greater than antigen with aluminum adjuvant. Utilizing an in vivo imaging system, Nano-11 was shown to remain at the injection site after administration and cleared gradually over the course of 3 weeks. Injection of Nano-11 induced a transient inflammatory response characterized by recruitment of a mixed population of inflammatory cells, predominantly monocytes and macrophages with relatively few neutrophils. Recruited Mac-2+macrophages efficiently phagocytized the majority of Nano-11 at the injection site. Fluorescently labeled Nano-11 was present in cells in the draining lymph nodes 1 day after injection, with the majority contained in migratory dendritic cells. Injection of ovalbumin adsorbed to Nano-11 resulted in an increase of ovalbumin-containing cells in draining lymph nodes. Nano-11 delivered more antigen to antigen-presenting cells on a per cell basis and demonstrated more specific targeting to highly immunopotentiating migratory dendritic cells compared with soluble or aluminum hydroxide adsorbed ovalbumin. These results support the efficacy of Nano-11 and its potential use as a next generation vaccine adjuvant.
DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients
Authors: Crujeiras A. B. , Diaz-Lagares A. , Sandoval J. , Milagro F. I. , Navas-Carretero S. , Carreira M. C. , Gomez A. , Hervas D. , Monteiro M. P. , Casanueva F. F. , Esteller M. , Martinez J. A. 
Published: February 2017

AbstractThe characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8–10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue.
Palindromic amplification of the ERBB2 oncogene in primary HER2-positive breast tumors
Authors: Marotta Michael , Onodera Taku , Johnson Jeffrey , Budd G. Thomas , Watanabe Takaaki , Cui Xiaojiang , Giuliano Armando E. , Niida Atsushi , Tanaka Hisashi 
Published: February 2017

AbstractOncogene amplification confers a growth advantage to tumor cells for clonal expansion. There are several, recurrently amplified oncogenes throughout the human genome. However, it remains unclear whether this recurrent amplification is solely a manifestation of increased fitness resulting from random amplification mechanisms, or if a genomic locus-specific amplification mechanism plays a role. Here we show that the ERBB2 oncogene at 17q12 is susceptible to palindromic gene amplification, a mechanism characterized by the inverted (palindromic) duplication of genomic segments, in HER2-positive breast tumors. We applied two genomic approaches to investigate amplification mechanisms: sequencing of DNA libraries enriched with tumor-derived palindromic DNA (Genome-wide Analysis of Palindrome Formation) and whole genome sequencing (WGS). We observed significant enrichment of palindromic DNA within amplified ERBB2 genomic segments. Palindromic DNA was particularly enriched at amplification peaks and at boundaries between amplified and normal copy-number regions. Thus, palindromic gene amplification shaped the amplified ERBB2 locus. The enrichment of palindromic DNA throughout the amplified segments leads us to propose that the ERBB2 locus is amplified through the mechanism that repeatedly generates palindromic DNA, such as Breakage-Fusion-Bridge cycles. The genomic architecture surrounding ERBB2 in the normal genome, such as segmental duplications, could promote the locus-specific mechanism.
The inhibition of lung cancer cell migration by AhR-regulated autophagy
Authors: Tsai Chi-Hao , Li Ching-Hao , Cheng Yu-Wen , Lee Chen-Chen , Liao Po-Lin , Lin Cheng-Hui , Huang Shih-Hsuan , Kang Jaw-Jou 
Published: February 2017

AbstractThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in multiple organs and tissues. Whereas AhR mediates the metabolism of xenobiotic and endogenous compounds, its novel function in cancer epithelial-mesenchymal transition (EMT) remains controversial. Autophagy also participates in tumour progression through its functions in cell homeostasis and facilitates adaptation to EMT progression. In the present study, we found that AhR-regulated autophagy positively modulates EMT in non-small cell lung cancer cells. The motility of A549, H1299, and CL1-5 cells were correlated with different AhR expression levels. Invasive potential and cell morphology also changed when AhR protein expression was altered. Moreover, AhR levels exerted a contrasting effect on autophagy potential. Autophagy was higher in CL1-5 and H1299 cells with lower AhR levels than in A549 cells. Both AhR overexpression and autophagy inhibition decreased CL1-5 metastasis in vivo. Furthermore, AhR promoted BNIP3 ubiquitination for proteasomal degradation. AhR silencing in A549 cells also reduced BNIP3 ubiquitination. Taken together, these results provide a novel insight into the cross-linking between AhR and autophagy, we addressed the mechanistic BNIP3 modulation by endogenous AhR, which affect cancer cell EMT progression.
Phosphorene quantum dot saturable absorbers for ultrafast fiber lasers
Authors: Du J. , Zhang M. , Guo Z. , Chen J. , Zhu X. , Hu G. , Peng P. , Zheng Z. , Zhang H. 
Published: February 2017

AbstractWe fabricate ultrasmall phosphorene quantum dots (PQDs) with an average size of 2.6 ± 0.9 nm using a liquid exfoliation method involving ultrasound probe sonication followed by bath sonication. By coupling the as-prepared PQDs with microfiber evanescent light field, the PQD-based saturable absorber (SA) device exhibits ultrafast nonlinear saturable absorption property, with an optical modulation depth of 8.1% at the telecommunication band. With the integration of the all-fiber PQD-based SA, a continuous-wave passively mode-locked erbium-doped (Er-doped) laser cavity delivers stable, self-starting pulses with a pulse duration of 0.88 ps and at the cavity repetition rate of 5.47 MHz. Our results contribute to the growing body of work studying the nonlinear optical properties of ultrasmall PQDs that present new opportunities of this two-dimensional (2D) nanomaterial for future ultrafast photonic technologies.
A novel BK channel-targeted peptide suppresses sound evoked activity in the mouse inferior colliculus
Authors: Scott L. L. , Brecht E. J. , Philpo A. , Iyer S. , Wu N. S. , Mihic S. J. , Aldrich R. W. , Pierce J. , Walton J. P. 
Published: February 2017

AbstractLarge conductance calcium-activated (BK) channels are broadly expressed in neurons and muscle where they modulate cellular activity. Decades of research support an interest in pharmaceutical applications for modulating BK channel function. Here we report a novel BK channel-targeted peptide with functional activity in vitro and in vivo. This 9-amino acid peptide, LS3, has a unique action, suppressing channel gating rather than blocking the pore of heterologously expressed human BK channels. With an IC50 in the high picomolar range, the apparent affinity is higher than known high affinity BK channel toxins. LS3 suppresses locomotor activity via a BK channel-specific mechanism in wild-type or BK channel-humanized Caenorhabditis elegans. Topical application on the dural surface of the auditory midbrain in mouse suppresses sound evoked neural activity, similar to a well-characterized pore blocker of the BK channel. Moreover, this novel ion channel-targeted peptide rapidly crosses the BBB after systemic delivery to modulate auditory processing. Thus, a potent BK channel peptide modulator is open to neurological applications, such as preventing audiogenic seizures that originate in the auditory midbrain.
Rabconnectin-3α is required for the morphological maturation of GnRH neurons and kisspeptin responsiveness
Authors: Tata Brooke K. , Harbulot Carole , Csaba Zsolt , Peineau Stéphane , Jacquier Sandrine , de Roux Nicolas 
Published: February 2017

AbstractA few hundred hypothalamic neurons form a complex network that controls reproduction in mammals by secreting gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH secretion are essential for pubertal onset. During the juvenile period, GnRH neurons undergo morphological remodeling, concomitantly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH. However, the link between GnRH neuron activity and their morphology remains unknown. Here, we show that brain expression levels of Dmxl2, which encodes the vesicular protein rabconnectin-3α, determine the capacity of GnRH neurons to be activated by kisspeptin and estradiol. We also demonstrate that Dmxl2 expression levels control the pruning of GnRH dendrites, highlighting an unexpected role for a vesicular protein in the maturation of GnRH neuronal network. This effect is mediated by rabconnectin-3α in neurons or glial cells afferent to GnRH neurons. The widespread expression of Dmxl2 in several brain areas raises the intriguing hypothesis that rabconnectin-3α could be involved in the maturation of other neuronal populations.
Application of pristine and doped SnO2 nanoparticles as a matrix for agro-hazardous material (organophosphate) detection
Authors: Khan Naushad , Athar Taimur , Fouad H. , Umar Ahmad , Ansari Z. A. , Ansari S. G. 
Published: February 2017

AbstractWith an increasing focus on applied research, series of single/composite materials are being investigated for device development to detect several hazardous, dangerous, and toxic molecules. Here, we report a preliminary attempt of an electrochemical sensor fabricated using pristine Ni and Cr–doped nano tin oxide material (SnO2) as a tool to detect agro-hazardous material, i.e. Organophosphate (OP, chlorpyrifos). The nanomaterial was synthesized using the solution method. Nickel and chromium were used as dopant during synthesis. The synthesized material was calcined at 1000 °C and characterized for morphological, structural, and elemental analysis that showed the formation of agglomerated nanosized particles of crystalline nature. Screen-printed films of powder obtained were used as a matrix for working electrodes in a cyclic voltammogram (CV) at various concentrations of organophosphates (0.01 to 100 ppm). The CV curves were obtained before and after the immobilization of acetylcholinesterase (AChE) on the nanomaterial matrix. An interference study was also conducted with hydroquinone to ascertain the selectivity. The preliminary study indicated that such material can be used as suitable matrix for a device that can easily detect OP to a level of 10 ppb and thus contributes to progress in terms of desired device technology for the food and agricultural-industries.
Untargeted metabolomics of colonic digests reveals kynurenine pathway metabolites, dityrosine and 3-dehydroxycarnitine as red versus white meat discriminating metabolites
Authors: Rombouts Caroline , Hemeryck Lieselot Y. , Van Hecke Thomas , De Smet Stefaan , De Vos Winnok H. , Vanhaecke Lynn 
Published: February 2017

AbstractEpidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers. Twenty-two metabolites were unequivocally associated with simulated colonic digestion of red meat. Several of these metabolites could mechanistically be linked to red meat-associated pathways including N’-formylkynurenine, kynurenine and kynurenic acid (all involved in tryptophan metabolism), the oxidative stress marker dityrosine, and 3-dehydroxycarnitine. In conclusion, the used MS-based metabolomics platform proved to be a powerful platform for detection of specific metabolites that improve the understanding of the causal relationship between red meat consumption and associated diseases.
WHO water quality standards Vs Synergic effect(s) of fluoride, heavy metals and hardness in drinking water on kidney tissues
Authors: Wasana Hewa M. S. , Perera Gamage D. R. K. , Gunawardena Panduka De S. , Fernando Palika S. , Bandara Jayasundera 
Published: February 2017

AbstractDespite WHO standards, waterborne diseases among the human being are rising alarmingly. It is known that the prolong exposure to contaminated water has major impact on public health. The effect of chemical contaminations in drinking water on human being is found to be chronic rather than acute and hence can be defined “consumption of contaminated drinking water could be a silent killer”. As the WHO recommended water quality standards are only for individual element and synergic effects of trace metals and anions have not been considered, investigation of synergic effects of trace metals and anions and their effect on human being is of prime important research. By an animal trial, we investigated the synergic effect(s) of heavy metals, aluminium, arsenic, fluoride and hardness in drinking water on kidney tissues of mice. Our investigation strongly suggests existing of a synergic effect especially among Cd, F and hardness of water which could lead to severe kidney damage in mice, even at WHO maximum recommended levels. Hence, the synergic effect(s) of trace metals, fluoride and hardness present in drinking water should be investigated meticulously when stipulating the water quality at WHO maximum recommended levels.
Cervical Pessary for Prevention of Preterm Birth: A Meta-Analysis
Authors: Jin Xin-Hang , Li Dan , Huang Li-Li 
Published: February 2017

AbstractTo investigate the efficacy of cervical pessary placement in preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton pregnancy and a short cervix, we searched literature in relevant databases. The meta-analysis of the 3 included trials (1412 women) showed cervical pessary placement did not reduce the risk of spontaneous preterm birth <34 weeks in these women (risk ratio (RR), 0.71; 95% confidence interval (CI), 0.21–2.43, P = 0.59; I2 = 90%). The sensitivity analyses by excluding one trial at one time showed the same results. This meta-analysis also showed that cervical pessary did not prevent preterm birth <34, 30, 28 weeks and was not associated with respiratory distress syndrome, necrotising enterocolitis, intraventricular haemorrhage, neonatal sepsis, retinopathy of prematurity, fetal death, neonatal death, perinatal death, birth weight <1500 g, birth weight <2500 g, premature preterm rupture of membranes, corticosteroid treatment for fetal maturation, and admission to neonatal intensive care unit. Although this meta-analysis showed cervical pessary placement did not reduce the risk of preterm birth in women with a singleton pregnancy and a short cervix, we could not confirm or refute this conclusion, and large-scale randomised controlled trials are urgently needed.