bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases
Authors: Liu Yixiang , Rose Joshua , Huang Shaojia , Hu Yangbo , Wu Qiong , Wang Dan , Li Conggang , Liu Maili , Zhou Pei , Jiang Ling 
Published: December 2017

AbstractHistidine kinases are key regulators in the bacterial two-component systems that mediate the cellular response to environmental changes. The vast majority of the sensor histidine kinases belong to the bifunctional HisKA family, displaying both kinase and phosphatase activities toward their substrates. The molecular mechanisms regulating the opposing activities of these enzymes are not well understood. Through a combined NMR and crystallographic study on the histidine kinase HK853 and its response regulator RR468 from Thermotoga maritima, here we report a pH-mediated conformational switch of HK853 that shuts off its phosphatase activity under acidic conditions. Such a pH-sensing mechanism is further demonstrated in the EnvZ-OmpR two-component system from Salmonella enterica in vitro and in vivo, which directly contributes to the bacterial infectivity. Our finding reveals a broadly conserved mechanism that regulates the phosphatase activity of the largest family of bifunctional histidine kinases in response to the change of environmental pH.
Relationship of corneal hysteresis and optic nerve parameters in healthy myopic subjects
Authors: Qiu Kunliang , Lu Xuehui , Zhang Riping , Wang Geng , Zhang Mingzhi 
Published: December 2017

AbstractThe association between corneal biomechanical properties and glaucoma is an area of much interest. We determined the relationship between corneal hysteresis (CH) and optic nerve parameters in healthy myopic subjects in the current study. CH was measured with Reichert Ocular Response Analyzer in 108 eyes from 108 healthy myopic subjects. All subjects received retinal nerve fiber layer and optic disc imaging Cirrus HD-OCT, GDx ECC, and Heidelberg Retina Tomograph II. None of the tested optic nerve parameters showed statistical significance with CH by using correlation analysis. For RNFL parameters, there was a negative but not statistically significant correlation between CH and average RNFL thickness obtained with OCT (r = −0.15, p = 0.13). For optic disc parameters, there was a negative but not statistically significant correlation between CH and rim area measured with OCT (r = −0.10, p = 0.29). The current study did not find any statistically significant relationship between CH and optic nerve parameters as measured by all three imaging modalities in healthy myopic eyes. Therefore, the relationship observed previously in glaucoma subjects is likely coming to fruition as optic nerve damage is caused by the disease.
Quantification of interacting cognate odorants with olfactory receptors in nanovesicles
Authors: Sanmartí-Espinal Marta , Iavicoli Patrizia , Calò Annalisa , Taulés Marta , Galve Roger , Marco M. Pilar , Samitier Josep 
Published: December 2017

AbstractThis study aims to improve our understanding of the interaction between olfactory receptors and odorants to develop highly selective biosensing devices. Natural nanovesicles (NVs) from Saccharomyces cerevisiae, ~100 nm in diameter, carrying either the human OR17-40 or the chimpanzee OR7D4 olfactory receptor (OR) tagged with the c-myc epitope at their N-terminus, are presented as model systems to quantify the interaction between odorant and olfactory receptors. The level of expression of olfactory receptors was determined at individual NVs using a novel competitive ELISA immunoassay comparing the values obtained against those from techniques involving the solubilization of cell membrane proteins and the identification of c-myc-carrying receptors. Surface Plasmon Resonance (SPR) measurements on L1 Biacore chips indicate that cognate odorants bind to their Ors, thereby quantifying the approximate number of odorants that interact with a given olfactory receptor. The selectivity of OR17-40-carrying NVs towards helional and OR7D4-carrying NVs towards androstenone has been proven in cross-check experiments with non-specific odorant molecules (heptanal and pentadecalactone, respectively) and in control receptors.
Identification of nonsense-mediated mRNA decay pathway as a critical regulator of p53 isoform β
Authors: Cowen Lauren E. , Tang Yi 
Published: December 2017

AbstractHuman TP53 gene encodes the tumor suppressor p53 and, via alternative splicing, the p53β and γ isoforms. Numerous studies have shown that p53β/γ can modulate p53 functions and are critically involved in regulation of cellular response to stress conditions. However, it is not fully understood how the β and γ isoforms are regulated following splicing. Using gene targeting and RNAi, we showed that depletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53β but had minimal effect on p53γ. Sequence analysis reveals the presence of unique features – key hallmarks of NMD targets in the p53β transcript, which was further confirmed in NMD reporter gene assays. By manipulating splicing components, we found that NMD activities are crucial to control p53β levels under conditions that favor its splicing. Our data demonstrate that the NMD and alternative splicing pathways regulate p53β in a synergistic manner, and NMD plays a critical role in the determination of the p53β following its splicing. As aberrant p53β expression and dysfunctional NMD are both implicated in cancers, our studies may provide a novel insight into the regulation of p53β in tumorigenic settings.
Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage
Authors: Chambers Anna R. , Pilati Nadia , Balaram Pooja , Large Charles H. , Kaczmarek Leonard K. , Polley Daniel B. 
Published: December 2017

AbstractHigher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent temporal coding deficits could be ameliorated through modulation of voltage-gated potassium (Kv) channels that regulate temporal firing patterns. Here, we characterize AUT00063, a pharmacological compound that modulates Kv3.1, a high-threshold channel expressed in fast-spiking neurons throughout the central auditory pathway. Patch clamp recordings from auditory brainstem neurons and in silico modeling revealed that application of AUT00063 reduced action potential timing variability and improved temporal coding precision. Systemic injections of AUT00063 in vivo improved auditory synchronization and supported more accurate decoding of temporal sound features in the inferior colliculus and auditory cortex in adult mice with a near-complete loss of auditory nerve afferent synapses in the contralateral ear. These findings suggest modulating Kv3.1 in central neurons could be a promising therapeutic approach to mitigate temporal processing deficits that commonly accompany aging, tinnitus, ototoxic drug exposure or noise damage.
Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate
Authors: Ohgaki Ryuichi , Teramura Yuji , Hayashi Daichi , Quan Lili , Okuda Suguru , Nagamori Shushi , Takai Madoka , Kanai Yoshikatsu 
Published: December 2017

AbstractVarious physiological and pathological processes are accompanied with the alteration of pH at extracellular juxtamembrane region. Accordingly, the methods to analyze the cell surface pH have been demanded in biological and medical sciences. In this study, we have established a novel methodology for cell surface pH imaging using poly(ethylene glycol)-phospholipid (PEG-lipid) as a core structure of ratiometric fluorescent probes. PEG-lipid is a synthetic amphiphilic polymer originally developed for the cell surface modification in transplantation therapy. Via its hydrophobic alkyl chains of the phospholipid moiety, PEG-lipid is, when applied extracellularly, spontaneously inserted into the plasma membrane and retained at the surface of the cells. We have demonstrated that the PEG-lipid conjugated with fluorescein isothiocyanate (FITC-PEG-lipid) can be used as a sensitive and reversible cell-surface-anchored pH probe between weakly alkaline and acidic pH with an excellent spatiotemporal resolution. The remarkably simple procedure for cell-surface labeling with FITC-PEG-lipid would also be advantageous when considering its application to high-throughputin vitroassay. This study further indicates that various probes useful for the investigation of juxtamembrane environments could also be developed by using PEG-lipid as the core structure for bio-membrane anchoring.
The β-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA2DS2-VaSc score
Authors: Hu Xiaofeng , Wang Junjun , Li Yaguo , Wu Jiong , Qiao Song , Xu Shanhu , Huang Jun , Chen Linhui 
Published: December 2017

AbstractPrevious work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677 C/T, FGB 455 G/A, and eNOS G298A) in 479 AF patients with CES and 580 age and sex-matched AF patients without CES. The multivariate analysis adjusted for potential confounders and demonstrated that FGB 455 G/A was independently associated with increased risk of CES in AF patients and the significance remained after Bonferroni correction in the additive, dominant, and recessive models with ORs of 1.548 (95% CI: 1.251–1.915, P = 0.001), 1.588 (95% CI: (1.226–2.057, P = 0.003), and 2.394 (95% CI: 1.357–4.223, P = 0.015), respectively. Plasma fibrinogen levels were significantly higher in patients with the A allele compared with patients with genotype of GG (3.29 ± 0.38 mg/dl vs. 2.87 ± 0.18 mg/dl, P < 0.001). We found for the first time that the A allele of FGB 455 G/A was a risk factor for CES in AF patients, probably by elevating the level of plasma fibrinogen.
A novel type I cystatin of parasite origin with atypical legumain-binding domain
Authors: Ilgová Jana , Jedličková Lucie , Dvořáková Hana , Benovics Michal , Mikeš Libor , Janda Lubomír , Vorel Jiří , Roudnický Pavel , Potěšil David , Zdráhal Zbyněk , Gelnar Milan , Kašný Martin 
Published: December 2017

AbstractParasite inhibitors of cysteine peptidases are known to influence a vast range of processes linked to a degradation of either the parasites’ own proteins or proteins native to their hosts. We characterise a novel type I cystatin (stefin) found in a sanguinivorous fish parasite Eudiplozoon nipponicum (Platyhelminthes: Monogenea). We have identified a transcript of its coding gene in the transcriptome of adult worms. Its amino acid sequence is similar to other stefins except for containing a legumain-binding domain, which is in this type of cystatins rather unusual. As expected, the recombinant form of E. nipponicum stefin (rEnStef) produced in Escherichia coli inhibits clan CA peptidases – cathepsins L and B of the worm – via the standard papain-binding domain. It also blocks haemoglobinolysis by cysteine peptidases in the worm’s excretory-secretory products and soluble extracts. Furthermore, we had confirmed its ability to inhibit clan CD asparaginyl endopeptidase (legumain). The presence of a native EnStef in the excretory-secretory products of adult worms, detected by mass spectrometry, suggests that this protein has an important biological function at the host-parasite interface. We discuss the inhibitor’s possible role in the regulation of blood digestion, modulation of antigen presentation, and in the regeneration of host tissues.
Assessment of low concentration wastewater treatment operations with dewatered alum sludge-based sequencing batch constructed wetland system
Authors: Kang Wei , Chai Hongxiang , Xiang Yu , Chen Wei , Shao Zhiyu , He Qiang 
Published: December 2017

AbstractCompetition of volatile fatty acids between anoxic denitrification and anaerobic phosphorus release is prominent. Therefore, low concentration wastewater has restricted effects on nitrogen and phosphorus removal. The purpose of this study is to treat dormitory sewage with a biochemical oxygen demand (BOD) ranging from 50 to 150 mg/L using dewatered alum sludge-based sequencing batch constructed wetland system. Vegetation in the wetland system was chosen to be Phragmites australis. Three parallel cases were carried out to assess impacts due to different hydraulic retention time (HRT) and artificial aeration. The results showed that this system is effective in removing total nitrogen (TN), ammonia nitrogen (NH3-N) and total phosphorus (TP) under different HRT. However, nitrous oxide (N2O) emission poses to be the greatest challenge in the high HRT cases. Artificial aeration could reduce N2O emission but is associated with high operational cost. Results indicate that dewatered alum sludge-based sequencing batch constructed wetland system is a promising bio-measure in the treatment of low concentration wastewater.
Seasonal pattern of influenza activity in a subtropical city, China, 2010–2015
Authors: Liu Xu-Xiang , Li Yahong , Zhu Yibing , Zhang Juanjuan , Li Xiaoru , Zhang Junqing , Zhao Kefu , Hu Mingxia , Qin Guoyou , Wang Xi-Ling 
Published: December 2017

AbstractInfluenza seasonality study is critical for policy-makers to choose an optimal time for influenza vaccination campaign, especially for subtropical regions where influenza seasonality and periodicity are unclear. In this study, we explored the seasonality and periodicity of influenza in Hefei, China during 2010 to 2015 using five proxies originated from three data sources of clinical surveillance of influenza-like illness (ILI), laboratory surveillance of influenza and death registration of pneumonia and influenza. We combined both wavelets analysis and de-linear-trend regression with Fourier harmonic terms to estimate seasonal characteristics of epidemic phase, peak time, amplitude, ratio of dominant seasonality. We found both annual cycle of influenza epidemics peaking in December-February and semi-annual cycle peaking in December-February and June-July in subtropical city Hefei, China. Compared to proxies developed by ILI and death registration data separately, influenza proxies incorporated laboratory surveillance data performed better seasonality and periodicity, especially in semi-annual periodicity in Hefei. Proxy of ILI consultation rate showed more timeliness peak than other proxies, and could be useful in developing the early warning model for influenza epidemics. Our study suggests to integrate clinical and laboratory surveillance of influenza for future influenza seasonality studies in subtropical regions.
An optogenetic arrhythmia model to study catecholaminergic polymorphic ventricular tachycardia mutations
Authors: Fischer Elisabeth , Gottschalk Alexander , Schüler Christina 
Published: December 2017

AbstractCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a condition of abnormal heart rhythm (arrhythmia), induced by physical activity or stress. Mutations in ryanodine receptor 2 (RyR2), a Ca2+ release channel located in the sarcoplasmic reticulum (SR), or calsequestrin 2 (CASQ2), a SR Ca2+ binding protein, are linked to CPVT. For specific drug development and to study distinct arrhythmias, simple models are required to implement and analyze such mutations. Here, we introduced CPVT inducing mutations into the pharynx of Caenorhabditis elegans, which we previously established as an optogenetically paced heart model. By electrophysiology and video-microscopy, we characterized mutations in csq-1 (CASQ2 homologue) and unc-68 (RyR2 homologue). csq-1 deletion impaired pharynx function and caused missed pumps during 3.7 Hz pacing. Deletion mutants of unc-68, and in particular the point mutant UNC-68(R4743C), analogous to the established human CPVT mutant RyR2(R4497C), were unable to follow 3.7 Hz pacing, with progressive defects during long stimulus trains. The pharynx either locked in pumping at half the pacing frequency or stopped pumping altogether, possibly due to UNC-68 leakiness and/or malfunctional SR Ca2+ homeostasis. Last, we could reverse this ‘worm arrhythmia’ by the benzothiazepine S107, establishing the nematode pharynx for studying specific CPVT mutations and for drug screening.
Direct Generation and Detection of Quantum Correlated Photons with 3.2 um Wavelength Spacing
Authors: Sua Yong Meng , Fan Heng , Shahverdi Amin , Chen Jia-Yang , Huang Yu-Ping 
Published: December 2017

AbstractQuantum correlated, highly non-degenerate photons can be used to synthesize disparate quantum nodes and link quantum processing over incompatible wavelengths, thereby constructing heterogeneous quantum systems for otherwise unattainable superior performance. Existing techniques for correlated photons have been concentrated in the visible and near-IR domains, with the photon pairs residing within one micron. Here, we demonstrate direct generation and detection of high-purity photon pairs at room temperature with 3.2 um wavelength spacing, one at 780 nm to match the rubidium D2 line, and the other at 3950 nm that falls in a transparent, low-scattering optical window for free space applications. The pairs are created via spontaneous parametric downconversion in a lithium niobate waveguide with specially designed geometry and periodic poling. The 780 nm photons are measured with a silicon avalanche photodiode, and the 3950 nm photons are measured with an upconversion photon detector using a similar waveguide, which attains 34% internal conversion efficiency. Quantum correlation measurement yields a high coincidence-to-accidental ratio of 54, which indicates the strong correlation with the extremely non-degenerate photon pairs. Our system bridges existing quantum technology to the challenging mid-IR regime, where unprecedented applications are expected in quantum metrology and sensing, quantum communications, medical diagnostics, and so on.
Strengthening face centered cubic crystals by annealing induced nano-twins
Authors: Roy Barna , Das Jayanta 
Published: December 2017

AbstractUsually, cold working strengthen metals and alloys by introducing large population of dislocations, whereas annealing of cold worked metal recovers the structure, annihilates dislocations, forms new strain-free grains, and results loss of strength. Here, we report annealing-hardening at temperature well below stress relieving and recrystallization temperatures in contrast to the typical behavior. A large amount of structural defects, such as dislocations, grain boundaries, twins, and stacking faults, have been introduced in nanostructured α-brass by cryorolling. The interaction and rearrangement of these defects upon annealing at 165–200 °C have been monitored at an interval of 1 minute. Large increase of the yield strength up to 578 MPa has been achieved in annealed specimens, which is 23% higher than that of as-cryorolled, and 425% higher than that of as-cast brass due to the evolution of nano-twins. Our approach shows a new avenue on strengthening fcc crystals by incorporating annealing induced nano-twins.
TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model
Authors: Ratay Michelle L. , Balmert Stephen C. , Acharya Abhinav P. , Greene Ashlee C. , Meyyappan Thiagarajan , Little Steven R. 
Published: December 2017

AbstractDry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body’s own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRImicrospheres;TGF-β1,Rapamycin (Rapa), andIL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.
The unfolded protein response impacts melanoma progression by enhancing FGF expression and can be antagonized by a chemical chaperone
Authors: Eigner Karin , Filik Yüksel , Mark Florian , Schütz Birgit , Klambauer Günter , Moriggl Richard , Hengstschläger Markus , Stangl Herbert , Mikula Mario , Röhrl Clemens 
Published: December 2017

AbstractThe mechanisms hallmarking melanoma progression are insufficiently understood. Here we studied the impact of the unfolded protein response (UPR) - a signalling cascade playing ambiguous roles in carcinogenesis - in melanoma malignancy. We identified isogenic patient-derived melanoma cell lines harboring BRAFV600E-mutations as a model system to study the role of intrinsic UPR in melanoma progression. We show that the activity of the three effector pathways of the UPR (ATF6, PERK and IRE1) was increased in metastatic compared to non-metastatic cells. Increased UPR-activity was associated with increased flexibility to cope with ER stress. The activity of the ATF6- and the PERK-, but not the IRE-pathway, correlated with poor survival in melanoma patients. Using whole-genome expression analysis, we show that the UPR is an inducer of FGF1 and FGF2 expression and cell migration. Antagonization of the UPR using the chemical chaperone 4-phenylbutyric acid (4-PBA) reduced FGF expression and inhibited cell migration and viability. Consistently, FGF expression positively correlated with the activity of ATF6 and PERK in human melanomas. We conclude that chronic UPR stimulates the FGF/FGF-receptor signalling axis and promotes melanoma progression. Hence, the development of potent chemical chaperones to antagonize the UPR might be a therapeutic approach to target melanoma.