bluuebunny/crossref_metadata_2025_split huggingface dataset:
Folate Metabolism Regulates Oligodendrocyte Survival and Differentiation by Modulating AMPKα Activity
Authors: Weng Qinjie , Wang Jiajia , Wang Jiaying , Tan Biqin , Wang Jing , Wang Haibo , Zheng Tao , Lu Q. Richard , Yang Bo , He Qiaojun 
Published: May 2017

AbstractFolate, an essential micronutrient, is a critical cofactor in one-carbon metabolism for many cellular pathways including DNA synthesis, metabolism and maintenance. Folate deficiency has been associated with an increased risk of neurological disease, cancer and cognitive dysfunction. Dihydrofolate reductase (DHFR) is a key enzyme to regulate folate metabolism, however folate/DHFR activity in oligodendrocyte development has not been fully understood. Here we show that folate enhances oligodendrocyte maturation both in vitro and in vivo, which is accompanied with upregulation of oligodendrocyte-specific DHFR expression. On the other hand, pharmacological inhibition of DHFR by methotrexate (MTX) causes severe defects in oligodendrocyte survival and differentiation, which could be reversed by folate intake. We further demonstrate that folate activates a metabolic regulator AMPKα to promote oligodendrocyte survival and differentiation. Moreover, activation of AMPKα partially rescues oligodendrocyte defects caused by DHFR-inhibition both in vitro and in vivo. Taken together, these findings identify a previously uncharacterized role of folate/DHFR/AMPKα axis in regulating oligodendrocyte survival and myelination during CNS development.
Multiple biomarker responses (serum biochemistry, oxidative stress, genotoxicity and histopathology) in Channa punctatus exposed to heavy metal loaded waste water
Authors: Javed Mehjbeen , Ahmad Md. Irshad , Usmani Nazura , Ahmad Masood 
Published: May 2017

AbstractExperiments were conducted to investigate the health of fish Channa punctatus inhabiting heavy metal-loaded waste water. Heavy metals in the order of Fe > Mn > Zn > Co > Ni > Cu = Cr were present in the waste water. Gills had high metal load followed by liver and then kidney. Albumin, albumin to globulin (A:G) ratio, triglyceride, high density lipoprotein (HDL) and very low density lipoprotein (VLDL) were found to be lower but phospholipid, low density lipoprotein (LDL), total protein, lipid and cholesterol were higher as compared to the reference. Oxidative stress markers such as superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST) and lipid peroxidation (LPO) were significantly higher in all tissues, whereas reduced glutathione (GSH) levels were comparatively low. Damage to DNA was observed with significantly higher mean tail length of comets in the exposed fish gill cells (30.9 µm) followed by liver (24.3 µm) and kidney (20.6 µm) as compared to reference fish (5.2, 4.8 and 5.9 µm respectively). Histopathology in gill, liver and kidney also showed marked damage. Integrated biochemical, oxidative stress, genotoxicity and histopathological findings are valuable biomarkers for native fish adaptive patterns, and monitoring of water quality/pollution of freshwater ecosystems.
Nuclear DNA markers for identification of Beluga and Sterlet sturgeons and their interspecific Bester hybrid
Authors: Havelka Miloš , Fujimoto Takafumi , Hagihara Seishi , Adachi Shinji , Arai Katsutoshi 
Published: May 2017

AbstractSturgeons (Acipenseriformes) are among the most endangered species in the world due to fragmentation and destruction of their natural habitats and to overexploitation, mainly for highly priced caviar. This has led to the development of sturgeon culture, originally for reintroduction, but more recently for caviar production. In both cases, accurate species identification is essential. We report a new tool for accurate identification of Huso huso and Acipenser ruthenus based on nuclear DNA markers. We employed ddRAD sequencing to identify species-specific nucleotide variants, which served as specific binding sites for diagnostic primers. The primers allowed identification of Huso huso and Acipenser ruthenus as well as their discrimination from A. baerii, A. schrenckii, A. gueldenstaedtii, A. stellatus, A. persicus, A. mikadoi, A. transmontanus, and H. dauricus and identification of A. ruthenus and H. huso hybrids with these species, except hybrid between A. ruthenus and A. stellatus. The species-specific primers also allowed identification of bester (H. huso × A. ruthenus), the most commercially exploited sturgeon hybrid. The tool, based on simple PCR and gel electrophoresis, is rapid, inexpensive, and reproducible. It will contribute to conservation of remaining wild populations of A. ruthenus and H. huso, as well as to traceability of their products.
The neuronal K+Cl− co-transporter 2 (Slc12a5) modulates insulin secretion
Authors: Kursan Shams , McMillen Timothy S. , Beesetty Pavani , Dias-Junior Eduardo , Almutairi Mohammed M. , Sajib Abu A. , Kozak J. Ashot , Aguilar-Bryan Lydia , Di Fulvio Mauricio 
Published: May 2017

AbstractIntracellular chloride concentration ([Cl−]i) in pancreatic β-cells is kept above electrochemical equilibrium due to the predominant functional presence of Cl− loaders such as the Na+K+2Cl− co-transporter 1 (Slc12a2) over Cl−extruders of unidentified nature. Using molecular cloning, RT-PCR, Western blotting, immunolocalization and in vitro functional assays, we establish that the “neuron-specific” K+Cl− co-transporter 2 (KCC2, Slc12a5) is expressed in several endocrine cells of the pancreatic islet, including glucagon secreting α-cells, but particularly in insulin-secreting β-cells, where we provide evidence for its role in the insulin secretory response. Three KCC2 splice variants were identified: the formerly described KCC2a and KCC2b along with a novel one lacking exon 25 (KCC2a-S25). This new variant is undetectable in brain or spinal cord, the only and most abundant known sources of KCC2. Inhibition of KCC2 activity in clonal MIN6 β-cells increases basal and glucose-stimulated insulin secretion and Ca2+ uptake in the presence of glibenclamide, an inhibitor of the ATP-dependent potassium (KATP)-channels, thus suggesting a possible mechanism underlying KCC2-dependent insulin release. We propose that the long-time considered “neuron-specific” KCC2 co-transporter is expressed in pancreatic islet β-cells where it modulates Ca2+-dependent insulin secretion.
Pharmacometabolomics for predicting variable busulfan exposure in paediatric haematopoietic stem cell transplantation patients
Authors: Kim Bora , Lee Ji Won , Hong Kyung Taek , Yu Kyung-Sang , Jang In-Jin , Park Kyung Duk , Shin Hee Young , Ahn Hyo Seop , Cho Joo-Youn , Kang Hyoung Jin 
Published: May 2017

AbstractOwing to its narrow therapeutic range and high pharmacokinetic variability, optimal dosing for busulfan is important to minimise overexposure-related systemic toxicity and underexposure-related graft failure. Using global metabolomics, we investigated biomarkers for predicting busulfan exposure. We analysed urine samples obtained before busulfan administration from 59 paediatric patients divided into 3 groups classified by area under the busulfan concentration-time curve (AUC), i.e., low-, medium-, and high-AUC groups. In the high-AUC group, deferoxamine metabolites were detected. Phenylacetylglutamine and two acylcarnitines were significantly lower in the high-AUC group than in the low-AUC group. Deferoxamine, an iron-chelating agent that lowers serum ferritin levels, was detected in the high-AUC group, indicating that those patients had high ferritin levels. Therefore, in a retrospective study of 130 paediatric patients, we confirmed our hypothesis that busulfan clearance (dose/AUC) and serum ferritin level has a negative correlation (r = −0.205, P = 0.019). Ferritin, acylcarnitine, and phenylacetylglutamine are associated with liver damage, including free radical formation, deregulation of hepatic mitochondrial β-oxidation, and hyperammonaemia. Our findings reveal potential biomarkers predictive of busulfan exposure and suggest that liver function may affect busulfan exposure.
Model-guided control of hippocampal discharges by local direct current stimulation
Authors: Mina Faten , Modolo Julien , Recher Fanny , Dieuset Gabriel , Biraben Arnaud , Benquet Pascal , Wendling Fabrice 
Published: May 2017

AbstractNeurostimulation is an emerging treatment for drug-resistant epilepsies when surgery is contraindicated. Recent clinical results demonstrate significant seizure frequency reduction in epileptic patients, however the mechanisms underlying this therapeutic effect are largely unknown. This study aimed at gaining insights into local direct current stimulation (LDCS) effects on hyperexcitable tissue, by i) analyzing the impact of electrical currents locally applied on epileptogenic brain regions, and ii) characterizing currents achieving an “anti-epileptic” effect (excitability reduction). First, a neural mass model of hippocampal circuits was extended to accurately reproduce the features of hippocampal paroxysmal discharges (HPD) observed in a mouse model of epilepsy. Second, model predictions regarding current intensity and stimulation polarity were confronted to in vivo mice recordings during LDCS (n = 8). The neural mass model was able to generate realistic hippocampal discharges. Simulation of LDCS in the model pointed at a significant decrease of simulated HPD (in duration and occurrence rate, not in amplitude) for cathodal stimulation, which was successfully verified experimentally in epileptic mice. Despite the simplicity of our stimulation protocol, these results contribute to a better understanding of clinical benefits observed in epileptic patients with implanted neurostimulators. Our results also provide further support for model-guided design of neuromodulation therapy.
Campanile Near-Field Probes Fabricated by Nanoimprint Lithography on the Facet of an Optical Fiber
Authors: Calafiore Giuseppe , Koshelev Alexander , Darlington Thomas P. , Borys Nicholas J. , Melli Mauro , Polyakov Aleksandr , Cantarella Giuseppe , Allen Frances I. , Lum Paul , Wong Ed , Sassolini Simone , Weber-Bargioni Alexander , Schuck P. James , Cabrini Stefano , Munechika Keiko 
Published: May 2017

AbstractOne of the major challenges to the widespread adoption of plasmonic and nano-optical devices in real-life applications is the difficulty to mass-fabricate nano-optical antennas in parallel and reproducible fashion, and the capability to precisely place nanoantennas into devices with nanometer-scale precision. In this study, we present a solution to this challenge using the state-of-the-art ultraviolet nanoimprint lithography (UV-NIL) to fabricate functional optical transformers onto the core of an optical fiber in a single step, mimicking the ‘campanile’ near-field probes. Imprinted probes were fabricated using a custom-built imprinter tool with co-axial alignment capability with sub <100 nm position accuracy, followed by a metallization step. Scanning electron micrographs confirm high imprint fidelity and precision with a thin residual layer to facilitate efficient optical coupling between the fiber and the imprinted optical transformer. The imprinted optical transformer probe was used in an actual NSOM measurement performing hyperspectral photoluminescence mapping of standard fluorescent beads. The calibration scans confirmed that imprinted probes enable sub-diffraction limited imaging with a spatial resolution consistent with the gap size. This novel nano-fabrication approach promises a low-cost, high-throughput, and reproducible manufacturing of advanced nano-optical devices.
Flexible and Self-Healing Aqueous Supercapacitors for Low Temperature Applications: Polyampholyte Gel Electrolytes with Biochar Electrodes
Authors: Li Xinda , Liu Li , Wang Xianzong , Ok Yong Sik , Elliott Janet A. W. , Chang Scott X. , Chung Hyun-Joong 
Published: May 2017

AbstractA flexible and self-healing supercapacitor with high energy density in low temperature operation was fabricated using a combination of biochar-based composite electrodes and a polyampholyte hydrogel electrolyte. Polyampholytes, a novel class of tough hydrogel, provide self-healing ability and mechanical flexibility, as well as low temperature operation for the aqueous electrolyte. Biochar is a carbon material produced from the low-temperature pyrolysis of biological wastes; the incorporation of reduced graphene oxide conferred mechanical integrity and electrical conductivity and hence the electrodes are called biochar-reduced-graphene-oxide (BC-RGO) electrodes. The fabricated supercapacitor showed high energy density of 30 Wh/kg with ~90% capacitance retention after 5000 charge–discharge cycles at room temperature at a power density of 50 W/kg. At −30 °C, the supercapacitor exhibited an energy density of 10.5 Wh/kg at a power density of 500 W/kg. The mechanism of the low-temperature performance excellence is likely to be associated with the concept of non-freezable water near the hydrophilic polymer chains, which can motivate future researches on the phase behaviour of water near polyampholyte chains. We conclude that the combination of the BC-RGO electrode and the polyampholyte hydrogel electrolyte is promising for supercapacitors for flexible electronics and for low temperature environments.
Identifying conformational changes with site-directed spin labeling reveals that the GTPase domain of HydF is a molecular switch
Authors: Galazzo Laura , Maso Lorenzo , De Rosa Edith , Bortolus Marco , Doni Davide , Acquasaliente Laura , De Filippis Vincenzo , Costantini Paola , Carbonera Donatella 
Published: May 2017

Abstract[FeFe]-hydrogenases catalyse the reduction of protons to hydrogen at a complex 2Fe[4Fe4S] center called H-cluster. The assembly of this active site is a multistep process involving three proteins, HydE, HydF and HydG. According to the current models, HydF has the key double role of scaffold, upon which the final H-cluster precursor is assembled, and carrier to transfer it to the target hydrogenase. The X-ray structure of HydF indicates that the protein is a homodimer with both monomers carrying two functional domains: a C-terminal FeS cluster-binding domain, where the precursor is assembled, and a N-terminal GTPase domain, whose exact contribution to cluster biogenesis and hydrogenase activation is still elusive. We previously obtained several hints suggesting that the binding of GTP to HydF could be involved in the interactions of this scaffold protein with the other maturases and with the hydrogenase itself. In this work, by means of site directed spin labeling coupled to EPR/PELDOR spectroscopy, we explored the conformational changes induced in a recombinant HydF protein by GTP binding, and provide the first clue that the HydF GTPase domain could be involved in the H-cluster assembly working as a molecular switch similarly to other known small GTPases.
Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation
Authors: Qu Kai , Zhang Xing , Lin Ting , Liu Tian , Wang Zhixin , Liu Sushun , Zhou Lei , Wei Jichao , Chang Hulin , Li Ke , Wang Zheng , Liu Chang , Wu Zheng 
Published: May 2017

AbstractPancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.
Intact word processing in developmental prosopagnosia
Authors: Burns Edwin J. , Bennetts Rachel J. , Bate Sarah , Wright Victoria C. , Weidemann Christoph T. , Tree Jeremy J. 
Published: May 2017

AbstractA wealth of evidence from behavioural, neuropsychological and neuroimaging research supports the view that face recognition is reliant upon a domain-specific network that does not process words. In contrast, the recent many-to-many model of visual recognition posits that brain areas involved in word and face recognition are functionally integrated. Developmental prosopagnosia (DP) is characterised by severe deficits in the recognition of faces, which the many-to-many model predicts should negatively affect word recognition. Alternatively, domain-specific accounts suggest that impairments in face and word processing need not go hand in hand. To test these possibilities, we ran a battery of 7 tasks examining word processing in a group of DP cases and controls. One of our prosopagnosia cases exhibited a severe reading impairment with delayed response times during reading aloud tasks, but not lexical decision tasks. Overall, however, we found no evidence of global word processing deficits in DP, consistent with a dissociation account for face and word processing.
Quantification of blood-brain barrier permeability by dynamic contrast-enhanced NIRS
Authors: Milej Daniel , Abdalmalak Androu , Desjardins Lise , Ahmed Hassaan , Lee Ting-Yim , Diop Mamadou , Lawrence Keith St. 
Published: May 2017

AbstractThe blood-brain barrier (BBB) is integral to maintaining a suitable microenvironment for neurons to function properly. Despite its importance, there are no bedside methods of assessing BBB disruption to help guide management of critical-care patients. The aim of this study was to demonstrate that dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) can quantify the permeability surface-area product (PS) of the BBB. Experiments were conducted in rats in which the BBB was opened by image-guided focused ultrasound. DCE-NIRS data were acquired with two dyes of different molecular weight, indocyanine green (ICG, 67 kDa) and 800CW carboxylate (IRDye, 1166 Da), and PS maps were generated by DCE computer tomography (CT) for comparison. Both dyes showed a strong correlation between measured PS values and sonication power (R2 = 0.95 and 0.92 for ICG and IRDye respectively), and the PS values for IRDye were in good agreement with CT values obtained with a contrast agent of similar molecular weight. These proof-of-principle experiments demonstrate that DCE NIRS can quantify BBB permeability. The next step in translating this method to critical care practice will be to adapt depth sensitive methods to minimize the effects of scalp contamination on NIRS PS values.
Increased cerebral expressions of MMPs, CLDN5, OCLN, ZO1 and AQPs are associated with brain edema following fatal heat stroke
Authors: Du Yu , Xu Jing-Tao , Jin Hong-Nian , Zhao Rui , Zhao Dong , Du Si-Hao , Xue Ye , Xie Xiao-Li , Wang Qi 
Published: May 2017

AbstractHuman brain samples were collected from 46 autopsy cases, including 23 fatal heat stroke cases and 23 age-matched controls. Nine candidate reference genes (PES1, POLR2A, IPO8, HMBS, SDHA, GAPDH, UBC, B2M, ACTB) were evaluated in the cerebral cortex of 10 forensic autopsy cases (5 heat stroke and 5 controls), using the geNorm module in qBaseplus software. SDHA, POLR2A, IPO8 and HMBS were identified as the most stable reference genes. Using these validated reference genes, mRNA expressions of Matrix metalloproteinases (MMPs, MMP2 and MMP9), Claudin5 (CLDN5), Occludin (OCLN), Zona occludens protein-1 (ZO1) and Aquaporins (AQPs, AQP1 and AQP4) in the cerebral cortex were examined. Relative mRNA quantification using Taqman real-time PCR assay demonstrated increased calibrated normalized relative quantity (CNRQ) values of MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke cases. Heat stroke cases showed an increase in brain water content, which was found to be positively correlated with MMP9, OCLN, ZO1 and CLDN5 mRNA. When using one conventional reference gene (GAPDH or ACTB) for normalization, no difference was detected between heat stroke and controls. In immunostaining, only AQP4 showed more intense staining in most heat stroke cases. The present study, for the first time, reports increased cerebral MMP9, CLDN5, OCLN, ZO1 and AQP4 in heat stroke and suggest a crucial role of reference gene selection when using postmortem human tissues.
Design, Fabrication and Characterization of Pressure-Responsive Films Based on The Orientation Dependence of Plasmonic Properties of Ag@Au Nanoplates
Authors: Fu Li-Shun , Wang Wen-Shou , Xu Cheng-Yan , Li Yao , Zhen Liang 
Published: May 2017

AbstractA novel pressure-responsive polymer composite film was developed based on Ag@Au composite nanoplates (NPLs) and polyvinylpyrrolidone (PVP) by using Au nanoparticles as concentration reference. The orientation change of Ag@Au NPLs is impelled by the deformation of polymer matrix under pressure, resulting in its localized surface plasmon resonance (LSPR) intensity change of in-plane dipolar peak. The intensity ratio between plasmon peak of Au nanoparticles and in-plane dipolar peak of Ag@Au NPLs relies on the intensity and duration of pressure. By adjusting the viscosity of the polymer, the orientation change of LSPR may respond to a wide range of stresses. This pressure sensitive film can be utilized to record the magnitude and distribution of pressure between two contacting surfaces via optical information.
Precision Radiology: Predicting longevity using feature engineering and deep learning methods in a radiomics framework
Authors: Oakden-Rayner Luke , Carneiro Gustavo , Bessen Taryn , Nascimento Jacinto C. , Bradley Andrew P. , Palmer Lyle J. 
Published: May 2017

AbstractPrecision medicine approaches rely on obtaining precise knowledge of the true state of health of an individual patient, which results from a combination of their genetic risks and environmental exposures. This approach is currently limited by the lack of effective and efficient non-invasive medical tests to define the full range of phenotypic variation associated with individual health. Such knowledge is critical for improved early intervention, for better treatment decisions, and for ameliorating the steadily worsening epidemic of chronic disease. We present proof-of-concept experiments to demonstrate how routinely acquired cross-sectional CT imaging may be used to predict patient longevity as a proxy for overall individual health and disease status using computer image analysis techniques. Despite the limitations of a modest dataset and the use of off-the-shelf machine learning methods, our results are comparable to previous ‘manual’ clinical methods for longevity prediction. This work demonstrates that radiomics techniques can be used to extract biomarkers relevant to one of the most widely used outcomes in epidemiological and clinical research – mortality, and that deep learning with convolutional neural networks can be usefully applied to radiomics research. Computer image analysis applied to routinely collected medical images offers substantial potential to enhance precision medicine initiatives.