bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-122 as a predictor of HBsAg seroclearance in hepatitis B and C dual infected patients treated with interferon and ribavirin
Authors: Yen Yi-Hao , Huang Chao-Min , Wei Kuo-Liang , Wang Jing-Houng , Lu Sheng-Nan , Lee Chuan-Mo , Hung Chao-Hung , Chen Chien-Hung , Tseng Po-Lin , Chang Kuo-Chin , Tsai Ming-Chao , Lin Ming-Tsung , Wu Cheng-Kun , Yang Cheng-Hong , Moi Sin-Hua , Cho Chung-Lung , Hu Tsung-Hui 
Published: September 2016

AbstractIt has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-α and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5.4 years. miR-122 was significantly lower in HBsAg seroclearance patients than in non-HBsAg seroclearance patients (P < 0.014). Multivariate analysis showed that miR-122 was an independent factor of HBsAg seroclearance (OR: 0.30, 95% CI: 0.09–0.98, P = 0.046). miR-122 was significantly higher in patients who were qHBsAg > 100 IU/mL versus ≤100 IU/mL (P < 0.001). We concluded that in patients with HBV-HCV dual infection with active hepatitis C, miR-122 was associated with HBsAg seroclearance after therapy and qHBsAg level before therapy, indicating that miR-122 plays key roles in modulating HBV replication.
Automated Internal Classification of Beadless Chinese ZhuJi Freshwater Pearls based on Optical Coherence Tomography Images
Authors: Zhou Yang , Liu Tiebing , Shi Yang , Chen Zhengwei , Mao Jianwei , Zhou Wujie 
Published: September 2016

AbstractOptical coherence tomography (OCT) has been applied to inspect the internal defect of beadless Chinese ZhuJi freshwater pearls. A novel fully automated algorithm is proposed to classify between normal and defective sub-layer in nacre layer. Our algorithm utilizes the graph segmentation approach to estimate the up and down boundaries of defect sub-layers from flattened and cropped image, and also proposes the strategy for edge and weight construction in segmentation process. The vertical gradients of boundary pixels are used to make grading decision. The algorithm is tested by typical pearl samples, and achieves 100% classification accuracy. The experiment result shows the feasibility and adaptability of the proposed approach, and proves that the OCT technique combined with proposed algorithm is a potential tool for fast and non-destructive diagnosis of internal structure of beadless pearl.
The H2/CH4 ratio during serpentinization cannot reliably identify biological signatures
Authors: Huang Ruifang , Sun Weidong , Liu Jinzhong , Ding Xing , Peng Shaobang , Zhan Wenhuan 
Published: September 2016

AbstractSerpentinization potentially contributes to the origin and evolution of life during early history of the Earth. Serpentinization produces molecular hydrogen (H2) that can be utilized by microorganisms to gain metabolic energy. Methane can be formed through reactions between molecular hydrogen and oxidized carbon (e.g., carbon dioxide) or through biotic processes. A simple criterion, the H2/CH4 ratio, has been proposed to differentiate abiotic from biotic methane, with values approximately larger than 40 for abiotic methane and values of <40 for biotic methane. The definition of the criterion was based on two serpentinization experiments at 200 °C and 0.3 kbar. However, it is not clear whether the criterion is applicable at a wider range of temperatures. In this study, we performed sixteen experiments at 311–500 °C and 3.0 kbar using natural ground peridotite. Our results demonstrate that the H2/CH4 ratios strongly depend on temperature. At 311 °C and 3.0 kbar, the H2/CH4 ratios ranged from 58 to 2,120, much greater than the critical value of 40. By contrast, at 400–500 °C, the H2/CH4 ratios were much lower, ranging from 0.1 to 8.2. The results of this study suggest that the H2/CH4 ratios cannot reliably discriminate abiotic from biotic methane.
Integrating occurrence and detectability patterns based on interview data: a case study for threatened mammals in Equatorial Guinea
Authors: Martínez-Martí Chele , Jiménez-Franco María V. , Royle J. Andrew , Palazón José A. , Calvo José F. 
Published: September 2016

AbstractOccurrence models that account for imperfect detection of species are increasingly used for estimating geographical range, for determining species-landscape relations and to prioritize conservation actions worldwide. In 2010, we conducted a large-scale survey in Río Muni, the mainland territory of Equatorial Guinea, which aimed to estimate the probabilities of occurrence and detection of threatened mammals based on environmental covariates, and to identify priority areas for conservation. Interviews with hunters were designed to record presence/absence data of seven species (golden cat, leopard, forest elephant, forest buffalo, western gorilla, chimpanzee and mandrill) in 225 sites throughout the region. We fitted single season occupancy models and recently developed models which also include false positive errors (i.e. species detected in places where it actually does not occur), which should provide more accurate estimates for most species, which are susceptible to mis-identification. Golden cat and leopard had the lowest occurrence rates in the region, whereas primates had the highest rates. All species, except gorilla, were affected negatively by human settlements. The southern half of Río Muni showed the highest occurrence of the species studied, and conservation strategies for ensuring the persistence of threatened mammals should be focused on this area.
RbTiOPO4 cascaded Raman operation with multiple Raman frequency shifts derived by Q-switched Nd:YAlO3 laser
Authors: Duan Yanmin , Zhu Haiyong , Zhang Yaoju , Zhang Ge , Zhang Jian , Tang Dingyuan , Kaminskii A. A. 
Published: September 2016

AbstractAn intra-cavity RbTiOPO4 (RTP) cascade Raman laser was demonstrated for efficient multi-order Stokes emission. An acousto-optic Q-switched Nd:YAlO3 laser at 1.08 μm was used as the pump source and a 20-mm-long x-cut RTP crystal was used as the Raman medium to meet the X(Z,Z)X Raman configuration. Multi-order Stokes with multiple Raman shifts (~271, ~559 and ~687 cm−1) were achieved in the output. Under an incident pump power of 9.5 W, a total average output power of 580 mW with a pulse repetition frequency of 10 kHz was obtained. The optical conversion efficiency is 6.1%. The results show that the RTP crystal can enrich laser spectral lines and generate high order Stokes light.
Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival
Authors: Volland Cornelia , Bremer Sebastian , Hellenkamp Kristian , Hartmann Nico , Dybkova Nataliya , Khadjeh Sara , Kutschenko Anna , Liebetanz David , Wagner Stefan , Unsöld Bernhard , Didié Michael , Toischer Karl , Sossalla Samuel , Hasenfuß Gerd , Seidler Tim 
Published: September 2016

AbstractTBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity.
Proteomic Analysis of Non-depleted Serum Proteins from Bottlenose Dolphins Uncovers a High Vanin-1 Phenotype
Authors: Sobolesky Philip , Parry Celeste , Boxall Baylye , Wells Randall , Venn-Watson Stephanie , Janech Michael G. 
Published: September 2016

AbstractTargeted approaches have been widely used to help explain physiological adaptations, but few studies have used non-targeted omics approaches to explore differences between diving marine mammals and terrestrial mammals. A rank comparison of undepleted serum proteins from common bottlenose dolphins (Tursiops truncatus) and pooled normal human serum led to the discovery of 11 proteins that appeared exclusive to dolphin serum. Compared to the comprehensive human plasma proteome, 5 of 11 serum proteins had a differential rank greater than 200. One of these proteins, Vanin-1, was quantified using parallel reaction monitoring in dolphins under human care and free-ranging dolphins. Dolphin serum Vanin-1 ranged between 31–106 μg/ml, which is 20–1000 times higher than concentrations reported for healthy humans. Serum Vanin-1 was also higher in dolphins under human care compared to free-ranging dolphins (64 ± 16 vs. 47 ± 12 μg/ml P < 0.05). Vanin-1 levels positively correlated with liver enzymes AST and ALT and negatively correlated with white blood cell counts and fibrinogen in free-ranging dolphins. Major differences exist in the circulating blood proteome of the bottlenose dolphin compared to terrestrial mammals and exploration of these differences in bottlenose dolphins and other marine mammals may identify veiled protective strategies to counter physiological stress.
Computational understanding and experimental characterization of twice-as-smart quadruplex ligands as chemical sensors of bacterial nucleotide second messengers
Authors: Zhou Jie , Roembke Benjamin T. , Paragi Gabor , Laguerre Aurélien , Sintim Herman O. , Fonseca Guerra Célia , Monchaud David 
Published: September 2016

AbstractA twice-as-smart ligand is a small molecule that experiences a structural switch upon interaction with its target (i.e., smart ligand) that concomitantly triggers its fluorescence (i.e., smart probe). Prototypes of twice-as-smart ligands were recently developed to track and label G-quadruplexes: these higher-order nucleic acid structures originate in the assembly of four guanine(G)-rich DNA or RNA strands, whose stability is imparted by the formation and the self-assembly of G-quartets. The first prototypes of twice-as-smart quadruplex ligands were designed to exploit the self-association of quartets, being themselves synthetic G-quartets. While their quadruplex recognition capability has been thoroughly documented, some doubts remain about the precise photophysical mechanism that underlies their peculiar spectroscopic properties. Here, we uncovered this mechanism via complete theoretical calculations. Collected information was then used to develop a novel application of twice-as-smart ligands, as efficient chemical sensors of bacterial signaling pathways via the fluorescent detection of naturally occurring extracellular quadruplexes formed by cyclic dimeric guanosine monophosphate (c-di-GMP).
Structural and histone binding ability characterization of the ARB2 domain of a histone deacetylase Hda1 from Saccharomyces cerevisiae
Authors: Shen Hui , Zhu Yuwei , Wang Chongyuan , Yan Hui , Teng Maikun , Li Xu 
Published: September 2016

AbstractHda1 is the catalytic core component of the H2B- and H3- specific histone deacetylase (HDAC) complex from Saccharomyces cerevisiae, which is involved in the epigenetic repression and plays a crucial role in transcriptional regulation and developmental events. Though the N-terminal catalytic HDAC domain of Hda1 is well characterized, the function of the C-terminal ARB2 domain remains unknown. In this study, we determine the crystal structure of the ARB2 domain from S. cerevisiae Hda1 at a resolution of 2.7 Å. The ARB2 domain displays an α/β sandwich architecture with an arm protruding outside. Two ARB2 domain molecules form a compact homo-dimer via the arm elements, and assemble as an inverse “V” shape. The pull-down and ITC results reveal that the ARB2 domain possesses the histone binding ability, recognizing both the H2A-H2B dimer and H3-H4 tetramer. Perturbation of the dimer interface abolishes the histone binding ability of the ARB2 domain, indicating that the unique dimer architecture of the ARB2 domain coincides with the function for anchoring to histone. Collectively, our data report the first structure of the ARB2 domain and disclose its histone binding ability, which is of benefit for understanding the deacetylation reaction catalyzed by the class II Hda1 HDAC complex.
Smoothing a rugged protein folding landscape by sequence-based redesign
Authors: Porebski Benjamin T. , Keleher Shani , Hollins Jeffrey J. , Nickson Adrian A. , Marijanovic Emilia M. , Borg Natalie A. , Costa Mauricio G. S. , Pearce Mary A. , Dai Weiwen , Zhu Liguang , Irving James A. , Hoke David E. , Kass Itamar , Whisstock James C. , Bottomley Stephen P. , Webb Geoffrey I. , McGowan Sheena , Buckle Ashley M. 
Published: September 2016

AbstractThe rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates and modifying scaffolds for use as protein therapeutics.
Using fluorescent dissolved organic matter to trace and distinguish the origin of Arctic surface waters
Authors: Gonçalves-Araujo Rafael , Granskog Mats A. , Bracher Astrid , Azetsu-Scott Kumiko , Dodd Paul A. , Stedmon Colin A. 
Published: September 2016

AbstractClimate change affects the Arctic with regards to permafrost thaw, sea-ice melt, alterations to the freshwater budget and increased export of terrestrial material to the Arctic Ocean. The Fram and Davis Straits represent the major gateways connecting the Arctic and Atlantic. Oceanographic surveys were performed in the Fram and Davis Straits and on the east Greenland Shelf (EGS), in late summer 2012/2013. Meteoric (fmw), sea-ice melt, Atlantic and Pacific water fractions were determined and the fluorescence properties of dissolved organic matter (FDOM) were characterized. In Fram Strait and EGS, a robust correlation between visible wavelength fluorescence andfmwwas apparent, suggesting it as a reliable tracer of polar waters. However, a pattern was observed which linked the organic matter characteristics to the origin of polar waters. At depth in Davis Strait, visible wavelength FDOM was correlated to apparent oxygen utilization (AOU) and traced deep-water DOM turnover. In surface waters FDOM characteristics could distinguish between surface waters from eastern (Atlantic + modified polar waters) and western (Canada-basin polar waters) Arctic sectors. The findings highlight the potential of designingin situmulti-channel DOM fluorometers to trace the freshwater origins and decipher water mass mixing dynamics in the region without laborious samples analyses.
TDP-43 aggregation mirrors TDP-43 knockdown, affecting the expression levels of a common set of proteins
Authors: Prpar Mihevc S. , Baralle Marco , Buratti Emanuele , Rogelj Boris 
Published: September 2016

AbstractTDP-43 protein plays an important role in regulating transcriptional repression, RNA metabolism and splicing. Typically it shuttles between the nucleus and the cytoplasm to perform its functions, while abnormal cytoplasmic aggregation of TDP-43 has been associated with neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). For the purpose of this study we selected a set of proteins that were misregulated following silencing of TDP-43 and analysed their expression in a TDP-43-aggregation model cell line HEK293 Flp-in Flag-TDP-43-12x-Q/N F4L. Following TDP-43 sequestration in insoluble aggregates, we observed higher nuclear levels of EIF4A3 and POLDIP3β, whereas nuclear levels of DNMT3A, HNRNPA3, PABPC1 and POLDIP3α dropped and cytoplasmic levels of RANBP1 dropped. In addition, immunofluorescence signal intensity quantifications showed increased nuclear expression of HNRNPL and YARS and downregulation of cytoplasmic DPCD. Furthermore, cytoplasmic levels of predominantly nuclear protein ALYREF increased. In conclusion, by identifying a common set of proteins that are differentially expressed in a similar manner in these two different conditions, we show that TDP-43 aggregation has a comparable effect to TDP-43 knockdown.
Integrating Multi-omics Data to Dissect Mechanisms of DNA repair Dysregulation in Breast Cancer
Authors: Liu Chao , Rohart Florian , Simpson Peter T. , Khanna Kum Kum , Ragan Mark A. , Lê Cao Kim-Anh 
Published: September 2016

AbstractDNA repair genes and pathways that are transcriptionally dysregulated in cancer provide the first line of evidence for the altered DNA repair status in tumours and hence have been explored intensively as a source for biomarker discovery. The molecular mechanisms underlying DNA repair dysregulation, however, have not been systematically investigated in any cancer type. In this study, we performed a statistical analysis to dissect the roles of DNA copy number alteration (CNA), DNA methylation (DM) at gene promoter regions and the expression changes of transcription factors (TFs) in the differential expression of individual DNA repair genes in normal versus tumour breast samples. These gene-level results were summarised at pathway level to assess whether different DNA repair pathways are affected in distinct manners. Our results suggest that CNA and expression changes of TFs are major causes of DNA repair dysregulation in breast cancer and that a subset of the identified TFs may exert global impacts on the dysregulation of multiple repair pathways. Our work hence provides novel insights into DNA repair dysregulation in breast cancer. These insights improve our understanding of the molecular basis of the DNA repair biomarkers identified thus far and have potential to inform future biomarker discovery.
Parametric analysis of colony morphology of non-labelled live human pluripotent stem cells for cell quality control
Authors: Kato Ryuji , Matsumoto Megumi , Sasaki Hiroto , Joto Risako , Okada Mai , Ikeda Yurika , Kanie Kei , Suga Mika , Kinehara Masaki , Yanagihara Kana , Liu Yujung , Uchio-Yamada Kozue , Fukuda Takayuki , Kii Hiroaki , Uozumi Takayuki , Honda Hiroyuki , Kiyota Yasujiro , Furue Miho K 
Published: September 2016

AbstractGiven the difficulties inherent in maintaining human pluripotent stem cells (hPSCs) in a healthy state, hPSCs should be routinely characterized using several established standard criteria during expansion for research or therapeutic purposes. hPSC colony morphology is typically considered an important criterion, but it is not evaluated quantitatively. Thus, we designed an unbiased method to evaluate hPSC colony morphology. This method involves a combination of automated non-labelled live-cell imaging and the implementation of morphological colony analysis algorithms with multiple parameters. To validate the utility of the quantitative evaluation method, a parent cell line exhibiting typical embryonic stem cell (ESC)-like morphology and an aberrant hPSC subclone demonstrating unusual colony morphology were used as models. According to statistical colony classification based on morphological parameters, colonies containing readily discernible areas of differentiation constituted a major classification cluster and were distinguishable from typical ESC-like colonies; similar results were obtained via classification based on global gene expression profiles. Thus, the morphological features of hPSC colonies are closely associated with cellular characteristics. Our quantitative evaluation method provides a biological definition of ‘hPSC colony morphology’, permits the non-invasive monitoring of hPSC conditions and is particularly useful for detecting variations in hPSC heterogeneity.
Ska3 Ensures Timely Mitotic Progression by Interacting Directly With Microtubules and Ska1 Microtubule Binding Domain
Authors: Abad Maria Alba , Zou Juan , Medina-Pritchard Bethan , Nigg Erich A. , Rappsilber Juri , Santamaria Anna , Jeyaprakash A. Arockia 
Published: September 2016

AbstractThe establishment of physical attachment between the kinetochore and dynamic spindle microtubules, which undergo cycles of polymerization and depolymerization generating straight and curved microtubule structures, is essential for accurate chromosome segregation. The Ndc80 and Ska complexes are the major microtubule-binding factors of the kinetochore responsible for maintaining chromosome-microtubule coupling during chromosome segregation. We previously showed that the Ska1 subunit of the Ska complex binds dynamic microtubules using multiple contact sites in a mode that allows conformation-independent binding. Here, we show that the Ska3 subunit is required to modulate the microtubule binding capability of the Ska complex (i) by directly interacting with tubulin monomers and (ii) indirectly by interacting with tubulin contacting regions of Ska1 suggesting an allosteric regulation. Perturbing either the Ska3-microtubule interaction or the Ska3-Ska1 interactions negatively influences microtubule binding by the Ska complex in vitro and affects the timely onset of anaphase in cells. Thus, Ska3 employs additional modulatory elements within the Ska complex to ensure robust kinetochore-microtubule attachments and timely progression of mitosis.