bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake
Authors: Cripps Michael J. , Hanna Katie , Lavilla Charlie , Sayers Sophie R. , Caton Paul W. , Sims Craig , De Girolamo Luigi , Sale Craig , Turner Mark D. 
Published: October 2017

AbstractThe worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes.
Diffusion tensor image features predict IDH genotype in newly diagnosed WHO grade II/III gliomas
Authors: Eichinger Paul , Alberts Esther , Delbridge Claire , Trebeschi Stefano , Valentinitsch Alexander , Bette Stefanie , Huber Thomas , Gempt Jens , Meyer Bernhard , Schlegel Juergen , Zimmer Claus , Kirschke Jan S. , Menze Bjoern H. , Wiestler Benedikt 
Published: October 2017

AbstractWe hypothesized that machine learning analysis based on texture information from the preoperative MRI can predict IDH mutational status in newly diagnosed WHO grade II and III gliomas. This retrospective study included in total 79 consecutive patients with a newly diagnosed WHO grade II or III glioma. Local binary pattern texture features were generated from preoperative B0 and fractional anisotropy (FA) diffusion tensor imaging. Using a training set of 59 patients, a single hidden layer neural network was then trained on the texture features to predict IDH status. The model was validated based on the prediction accuracy calculated in a previously unseen set of 20 gliomas. Prediction accuracy of the generated model was 92% (54/59 cases; AUC = 0.921) in the training and 95% (19/20; AUC = 0.952) in the validation cohort. The ten most important features were comprised of tumor size and both B0 and FA texture information, underlining the joint contribution of imaging data to classification. Machine learning analysis of DTI texture information and tumor size reliably predicts IDH status in preoperative MRI of gliomas. Such information may increasingly support individualized surgical strategies, supplement pathological analysis and highlight the potential of radiogenomics.
Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy
Authors: Nejadmoghaddam Mohammad-Reza , Zarnani Amir-Hassan , Ghahremanzadeh Ramin , Ghods Roya , Mahmoudian Jafar , Yousefi Maryam , Nazari Mahboobeh , Ghahremani Mohammad Hossein , Abolhasani Maryam , Anissian Ali , Mahmoudi Morteza , Dinarvand Rassoul 
Published: October 2017

AbstractOur recent findings strongly support the idea of PLAC1 being as a potential immunotherapeutic target in prostate cancer (PCa). Here, we have generated and evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC) for targeted immunotherapy of PCa. Prostate cancer cells express considerable levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but not in LS180 cells, the negative control. PLAC1 binding induced rapid internalization of the antibody within a few minutes which reached to about 50% after 15 min and almost completed within an hour. After SN38 conjugation to antibody, a drug-antibody ratio (DAR) of about 5.5 was achieved without apparent negative effect on antibody affinity to cell surface antigen. The ADC retained intrinsic antibody activity and showed enhanced and selective cytotoxicity with an IC50 of 62 nM which was about 15-fold lower compared to free drug. Anti-PLAC1-ADC induced apoptosis in human primary prostate cancer cells and prostate cell lines. No apparent cytotoxic effect was observed inin vivoanimal safety experiments. Our newly developed anti-PLAC1-based ADCs might pave the way for a reliable, efficient, and novel immunotherapeutic modality for patients with PCa.
Portable biosensor for monitoring cortisol in low-volume perspired human sweat
Authors: Kinnamon David , Ghanta Ramesh , Lin Kai-Chun , Muthukumar Sriram , Prasad Shalini 
Published: October 2017

AbstractA non-faradaic label-free cortisol biosensor was demonstrated using MoS2 nanosheets integrated into a nanoporous flexible electrode system. Low volume (1–5 μL) sensing was achieved through use of a novel sensor stack design comprised of vertically aligned metal electrodes confining semi-conductive MoS2 nanosheets. The MoS2 nanosheets were surface functionalized with cortisol antibodies towards developing an affinity biosensor specific to the physiological relevant range of cortisol (8.16 to 141.7 ng/mL) in perspired human sweat. Sensing was achieved by measuring impedance changes associated with cortisol binding along the MoS2 nanosheet interface using electrochemical impedance spectroscopy. The sensor demonstrated a dynamic range from 1–500 ng/mL with a limit of detection of 1 ng/mL. A specificity study was conducted using a metabolite expressed in human sweat, Ethyl Glucuronide. Continuous dosing studies were performed during which the sensor was able to discriminate between four cortisol concentration ranges (0.5, 5, 50, 500 ng/mL) for a 3+ hour duration. Translatability of the sensor was shown with a portable form factor device, demonstrating a comparable dynamic range and limit of detection for the sensor. The device demonstrated a R2 correlation value of 0.998 when comparing measurements to the reported impedance values of the benchtop instrumentation.
Long-term Cyclability of Substoichiometric Silicon Nitride Thin Film Anodes for Li-ion Batteries
Authors: Ulvestad Asbjørn , Andersen Hanne Flåten , Mæhlen Jan Petter , Prytz Øystein , Kirkengen Martin 
Published: October 2017

AbstractSilicon has been the subject of an extensive research effort aimed at developing new anode materials for lithium ion batteries due to its large specific and volumetric capacity. However, commercial use is limited by a number of degradation problems, many of which are related to the large volume change the material undergoes during cycling in combination with limited lithium-diffusivity. Silicon rich silicon oxides (SiOx), which converts into active silicon and inactive lithium oxide during the initial lithiation, have attracted some attention as a possible solution to these issues. In this work we present an investigation of silicon rich amorphous silicon nitride (a-SiNx) as an alternative convertible anode material. Amorphous SiN0.89 thin films deposited by plasma enhanced chemical vapour deposition show reversible reactions with lithium when cycled between 0.05 and 1.0 V vs. Li+/Li. This material delivers a reversible capacity of approximately 1,200 mAh/g and exhibits excellent cycling stability, with 41 nm a-SiN0.89 thin film electrodes showing negligible capacity degradation over more than 2,400 cycles.
MG-132 reduces virus release in Bovine herpesvirus-1 infection
Authors: Fiorito Filomena , Iovane Valentina , Cantiello Antonietta , Marullo Annarosaria , De Martino Luisa , Iovane Giuseppe 
Published: October 2017

AbstractBovine herpesvirus 1 (BoHV-1) can provoke conjunctivitis, abortions and shipping fever. BoHV-1 infection can also cause immunosuppression and increased susceptibility to secondary bacterial infections, leading to pneumonia and occasionally to death. Herein, we investigated the influence of MG-132, a proteasome inhibitor, on BoHV-1 infection in bovine kidney (MDBK) cells. Infection of MDBK cells with BoHV-1 induces apoptotic cell death that enhances virus release. Whereas, MG-132 inhibited virus-induced apoptosis and stimulated autophagy. Protein expression of viral infected cell protein 0 (bICP0), which is constitutively expressed during infection and is able to stimulate Nuclear factor kappa B (NF-κB), was completely inhibited by MG-132. These results were accompanied by a significant delay in the NF-κB activation. Interestingly, the efficient virus release provoked by BoHV-1-induced apoptosis was significantly reduced by MG-132. Overall, this study suggests that MG-132, through the activation of autophagy, may limit BoHV-1 replication during productive infection, by providing an antiviral defense mechanism.
The Role of Chromatin Density in Cell Population Heterogeneity during Stem Cell Differentiation
Authors: Golkaram Mahdi , Jang Jiwon , Hellander Stefan , Kosik Kenneth S. , Petzold Linda R. 
Published: October 2017

AbstractWe incorporate three-dimensional (3D) conformation of chromosome (Hi-C) and single-cell RNA sequencing data together with discrete stochastic simulation, to explore the role of chromatin reorganization in determining gene expression heterogeneity during development. While previous research has emphasized the importance of chromatin architecture on activation and suppression of certain regulatory genes and gene networks, our study demonstrates how chromatin remodeling can dictate gene expression distribution by folding into distinct topological domains. We hypothesize that the local DNA density during differentiation accentuate transcriptional bursting due to the crowding effect of chromatin. This phenomenon yields a heterogeneous cell population, thereby increasing the potential of differentiation of the stem cells.
Ultrasensitive, high-dynamic-range and broadband strain sensing by time-of-flight detection with femtosecond-laser frequency combs
Authors: Lu Xing , Zhang Shuangyou , Chen Xing , Kwon Dohyeon , Jeon Chan-Gi , Zhang Zhigang , Kim Jungwon , Shi Kebin 
Published: October 2017

AbstractUltrahigh-resolution optical strain sensors provide powerful tools in various scientific and engineering fields, ranging from long-baseline interferometers to civil and aerospace industries. Here we demonstrate an ultrahigh-resolution fibre strain sensing method by directly detecting the time-of-flight (TOF) change of the optical pulse train generated from a free-running passively mode-locked laser (MLL) frequency comb. We achieved a local strain resolution of 18 pε/Hz1/2 and 1.9 pε/Hz1/2 at 1 Hz and 3 kHz, respectively, with large dynamic range of >154 dB at 3 kHz. For remote-point sensing at 1-km distance, 80 pε/Hz1/2 (at 1 Hz) and 2.2 pε/Hz1/2 (at 3 kHz) resolution is demonstrated. While attaining both ultrahigh resolution and large dynamic range, the demonstrated method can be readily extended for multiple-point sensing as well by taking advantage of the broad optical comb spectra. These advantages may allow various applications of this sensor in geophysical science, structural health monitoring, and underwater science.
Switching to PegIFNα-2b leads to HBsAg loss in patients with low HBsAg levels and HBV DNA suppressed by NAs
Authors: Huang Jing , Zhang Ka , Chen Wenli , Liao Jinyao , Luo Xiaodan , Chen Ren 
Published: October 2017

AbstractPatients with low hepatitis B surface antigen (HBsAg) levels and hepatitis B virus (HBV) DNA suppression by nucleos(t)ide analogues (NAs) achieve high rate of HBsAg loss through switching to PegIFNα in pre-registration study. The aim of this study was to achieve higher rate of HBsAg loss through extended PegIFN treatment. 98 patients with HBsAg < 2,000 IU/ml and HBV DNA < 20 IU/ml were randomized to receive PegIFNα-2b or continuing NA therapy for 60 weeks. At the end of treatment (EOT) and end of follow-up (EOF), only patients who switched to PegIFNα-2b achieved HBsAg loss (32.6%) and HBsAg seroconversion (27.9% and 25.6%). Patients who switched to PegIFNα-2b also achieved higher HBeAg seroconversion rates (65.1%) and HBeAg loss (81.4% and 90.7%) than those who continued NAs treatment. On-treatment HBsAg declines predicted the responses at EOT, and HBsAg declines at post-baseline times predicted the responses at EOF. The rates of responses were not increased through extended PegIFNα treatment. For patients with low HBsAg and HBV suppression with NAs, switching to PegIFNα-2b significantly increased the rates of HBsAg loss and HBsAg seroconversion. HBsAg decline can predict the response of switching to PegIFNα-2b following from NAs.
High resolution, high speed, long working distance, large field of view confocal fluorescence microscope
Authors: Pacheco Shaun , Wang Chengliang , Chawla Monica K. , Nguyen Minhkhoi , Baggett Brend K. , Utzinger Urs , Barnes Carol A. , Liang Rongguang 
Published: October 2017

AbstractConfocal fluorescence microscopy is often used in brain imaging experiments, however conventional confocal microscopes are limited in their field of view, working distance, and speed for high resolution imaging. We report here the development of a novel high resolution, high speed, long working distance, and large field of view confocal fluorescence microscope (H2L2-CFM) with the capability of multi-region and multifocal imaging. To demonstrate the concept, a 0.5 numerical aperture (NA) confocal fluorescence microscope is prototyped with a 3 mm × 3 mm field of view and 12 mm working distance, an array of 9 beams is scanned over the field of view in 9 different regions to speed up the acquisition time by a factor of 9. We test this custom designed confocal fluorescence microscope for future use with brain clarification methods to image large volumes of the brain at subcellular resolution. This multi-region and multi-spot imaging method can be used in other imaging modalities, such as multiphoton microscopes, and the field of view can be extended well beyond 12 mm × 12 mm.
Fabrication of AO/LDH fluorescence composite and its detection of Hg2+ in water
Authors: Liu Meng , Lv Guocheng , Mei Lefu , Wei Yanke , Liu Jieyuan , Li Zhaohui , Liao Libing 
Published: October 2017

AbstractDivalent mercury ion (Hg2+) is one of the most common pollutants in water with high toxicity and significant bioaccumulation, for which sensitive and selective detection methods are highly necessary to carry out its detection and quantification. Fluorescence detection by organic dyes is a simple and rapid method in pollutant analyses and is limited because of quenching caused by aggregation dye molecules. Hydrotalcite (LDH) is one of the most excellent carrier materials. In this study, an organic dye acridine orange (AO) was successfully loaded on the LDH layers, which significantly inhibited fluorescence quenching of AO. The composite AO/LDH reaches the highest fluorescence intensity when the AO initial concentration is 5 mg/L. With its enhanced fluorescent property, the composite powder was fabricated to fluorescence test papers. The maximal fluorescence intensity was achieved with a pulp to AO/LDH ratio of 1:5 which can be used to detect Hg2+ in water by naked eyes. Hg2+ in aqueous solution can be detected by instruments in the range of 0.5 to 150 mM. The novelty of this study lies on both the development of a new type of mineral-dye composite material, as well as its practical applications for fast detection.
Therapy of corneal endothelial dysfunction with corneal endothelial cell-like cells derived from skin-derived precursors
Authors: Shen Lin , Sun Peng , Zhang Canwei , Yang Le , Du Liqun , Wu Xinyi 
Published: October 2017

AbstractCorneal endothelial dysfunction occurs when corneal endothelial cells (CECs) are dramatically lost and eventually results in vision loss. Corneal transplantation is the only solution at present. However, corneal transplantation requires a fresh human cornea and there is a worldwide shortage of donors. Therefore, finding new functional CECs to replace human CECs is urgent. Skin-derived precursors (SKPs) can be easily acquired and have multiple differential potential. We co-cultured human SKPs with B4G12 cells in serum-free medium and obtained abundant CEC-like cells which had similar morphology and characteristic to human CECs. CEC-like cells exerted excellent therapeutic effect when they were transplanted into rabbit and monkey corneal endothelial dysfunction models by injection method. This protocol enables efficient production of CEC-like cells from SKPs. The renewable cell source, novel derivation method and simple treatment strategy may lead to potential applications in cell replacement therapy for corneal endothelial dysfunction.
Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3 receptor degradation
Authors: Torrealba Natalia , Navarro-Marquez Mario , Garrido Valeria , Pedrozo Zully , Romero Diego , Eura Yuka , Villalobos Elisa , Roa Juan Carlos , Chiong Mario , Kokame Koichi , Lavandero Sergio 
Published: October 2017

AbstractCardiac hypertrophy is an adaptive response triggered by pathological stimuli. Regulation of the synthesis and the degradation of the Ca2+ channel inositol 1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy. Herpud1, a component of the endoplasmic reticulum-associated degradation (ERAD) complex, participates in IP3R1 degradation and Ca2+ signaling, but the cardiac function of Herpud1 remains unknown. We hypothesize that Herpud1 acts as a negative regulator of cardiac hypertrophy by regulating IP3R protein levels. Our results show that Herpud1-knockout mice exhibit cardiac hypertrophy and dysfunction and that decreased Herpud1 protein levels lead to elevated levels of hypertrophic markers in cultured rat cardiomyocytes. In addition, IP3R levels were elevated both in Herpud1-knockout mice and Herpud1 siRNA-treated rat cardiomyocytes. The latter treatment also led to elevated cytosolic and nuclear Ca2+ levels. In summary, the absence of Herpud1 generates a pathological hypertrophic phenotype by regulating IP3R protein levels. Herpud1 is a novel negative regulator of pathological cardiac hypertrophy.
Surface Decoration of Pt Nanoparticles via ALD with TiO2 Protective Layer on Polymeric Nanofibers as Flexible and Reusable Heterogeneous Nanocatalysts
Authors: Celebioglu Asli , Ranjith Kugalur Shanmugam , Eren Hamit , Biyikli Necmi , Uyar Tamer 
Published: October 2017

AbstractCoupling the functional nanoheterostructures over the flexible polymeric nanofibrous membranes through electrospinning followed by the atomic layer deposition (ALD), here we presented a high surface area platform as flexible and reusable heterogeneous nanocatalysts. Here, we show the ALD of titanium dioxide (TiO2) protective nanolayer onto the electrospun polyacrylonitrile (PAN) nanofibrous web and then platinum nanoparticles (Pt-NP) decoration was performed by ALD onto TiO2 coated PAN nanofibers. The free-standing and flexible Pt-NP/TiO2-PAN nanofibrous web showed the enhancive reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) within 45 seconds though the hydrogenation process with the degradation rate of 0.1102 s−1. The TiO2 protective layer on the PAN polymeric nanofibers was presented as an effective route to enhance the attachment of Pt-NP and to improve the structure stability of polymeric nanofibrous substrate. Commendable enhancement in the catalytic activity with the catalytic dosage and the durability after the reusing cycles were investigated over the reduction of 4-NP. Even after multiple usage, the Pt-NP/TiO2-PAN nanofibrous webs were stable with the flexible nature with the presence of Pt and TiO2 on its surface.
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis
Authors: Ferreira Mónica , Boens Shannah , Winkler Claudia , Szekér Kathelijne , Verbinnen Iris , Van Eynde Aleyde , Fardilha Margarida , Bollen Mathieu 
Published: October 2017

AbstractNIPP1 is one of the major nuclear interactors of protein phosphatase PP1. The deletion of NIPP1 in mice is early embryonic lethal, which has precluded functional studies in adult tissues. Hence, we have generated an inducible NIPP1 knockout model using a tamoxifen-inducible Cre recombinase transgene. The inactivation of the NIPP1 encoding alleles (Ppp1r8) in adult mice occurred very efficiently in testis and resulted in a gradual loss of germ cells, culminating in a Sertoli-cell only phenotype. Before the overt development of this phenotype Ppp1r8
−/−
testis showed a decreased proliferation and survival capacity of cells of the spermatogenic lineage. A reduced proliferation was also detected after the tamoxifen-induced removal of NIPP1 from cultured testis slices and isolated germ cells enriched for undifferentiated spermatogonia, hinting at a testis-intrinsic defect. Consistent with the observed phenotype, RNA sequencing identified changes in the transcript levels of cell-cycle and apoptosis regulating genes in NIPP1-depleted testis. We conclude that NIPP1 is essential for mammalian spermatogenesis because it is indispensable for the proliferation and survival of progenitor germ cells, including (un)differentiated spermatogonia.
The polyglutamine protein ataxin-3 enables normal growth under heat shock conditions in the methylotrophic yeast Pichia pastoris
Authors: Bonanomi Marcella , Roffia Valentina , De Palma Antonella , Lombardi Alessio , Aprile Francesco Antonio , Visentin Cristina , Tortora Paolo , Mauri Pierluigi , Regonesi Maria Elena 
Published: October 2017

AbstractThe protein ataxin-3 carries a polyglutamine stretch close to the C-terminus that triggers a neurodegenerative disease in humans when its length exceeds a critical threshold. A role as a transcriptional regulator but also as a ubiquitin hydrolase has been proposed for this protein. Here, we report that, when expressed in the yeast Pichia pastoris, full-length ataxin-3 enabled almost normal growth at 37 °C, well above the physiological optimum of 30 °C. The N-terminal Josephin domain (JD) was also effective but significantly less, whereas catalytically inactive JD was completely ineffective. Based on MudPIT proteomic analysis, we observed that the strain expressing full-length, functional ataxin-3 displayed persistent upregulation of enzymes involved in mitochondrial energy metabolism during growth at 37 °C compared with the strain transformed with the empty vector. Concurrently, in the transformed strain intracellular ATP levels at 37 °C were even higher than normal ones at 30 °C. Elevated ATP was also paralleled by upregulation of enzymes involved in both protein biosynthesis and biosynthetic pathways, as well as of several stress-induced proteins. A similar pattern was observed when comparing a strain expressing JD with another expressing its catalytically inactive counterpart. We suggest that such effects mostly result from mechanisms of transcriptional regulation.