bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese
Authors: Urayama Kevin Y. , Takagi Masatoshi , Kawaguchi Takahisa , Matsuo Keitaro , Tanaka Yoichi , Ayukawa Yoko , Arakawa Yuki , Hasegawa Daisuke , Yuza Yuki , Kaneko Takashi , Noguchi Yasushi , Taneyama Yuichi , Ota Setsuo , Inukai Takeshi , Yanagimachi Masakatsu , Keino Dai , Koike Kazutoshi , Toyama Daisuke , Nakazawa Yozo , Kurosawa Hidemitsu , Nakamura Kozue , Moriwaki Koichi , Goto Hiroaki , Sekinaka Yujin , Morita Daisuke , Kato Motohiro , Takita Junko , Tanaka Toshihiro , Inazawa Johji , Koh Katsuyoshi , Ishida Yasushi , Ohara Akira , Mizutani Shuki , Matsuda Fumihiko , Manabe Atsushi 
Published: January 2018

AbstractGenome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0–19 years) previously enrolled onto a Tokyo Children’s Cancer Study Group trial were collected during 2013–2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center Study were combined, and association analyses across 10 previous GWAS-identified regions were performed after targeted SNP imputation. Linkage disequilibrium (LD) patterns in Japanese and other populations were evaluated using the varLD score based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84, P = 6 × 10−17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 × 10−4) directly transferred to Japanese, and the IKZF1 association was detected by an alternate SNP (rs1451367, OR = 1.52, P = 2 × 10−6). Marked regional LD differences between Japanese and Europeans was observed for most of the remaining loci for which associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This study represents a first step towards characterizing the role of genetic susceptibility in childhood ALL risk in Japanese.
Study on regeneration of waste powder activated carbon through pyrolysis and its adsorption capacity of phosphorus
Authors: Li Yi , Jin Hailan , Liu Wenbo , Su Hang , Lu Yao , Li Jianfen 
Published: January 2018

AbstractThe regeneration of WPAC through pyrolysis and its adsorption capacity of phosphorus were studied. The optimum conditions for WPAC regeneration were 650 °C and 2 h which resulted in a recovery of BET surface and total pore volume with a value of 1161.4 m2/g and 1.2176 m3/g. WPAC had a maximum PO43−-P adsorption capacity of 9.65 mg/g which was 48.93% of PAC, while RWPAC had a maximum PO43−-P adsorption capacity of 15.31 mg/g which was 77.64% of PAC. The kinetic analysis revealed that Langmuir model could well describe the adsorption process of PAC, WPAC and RWPAC on PO43−-P and the PO43−-P adsorption followed the pseudo-second-order model.
Circulating microRNA signature for the diagnosis of childhood dilated cardiomyopathy
Authors: Jiao Meng , You Hong-Zhao , Yang Xin-Ying , Yuan Hui , Li Yu-Lin , Liu Wen-Xian , Jin Mei , Du Jie 
Published: January 2018

AbstractCirculating miRNAs are proposed as a biomarker of heart disease. This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12). The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated. Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects. Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction. This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
Authors: Sclafani Francesco , Chau Ian , Cunningham David , Hahne Jens C. , Vlachogiannis George , Eltahir Zakaria , Lampis Andrea , Braconi Chiara , Kalaitzaki Eleftheria , De Castro David Gonzalez , Wotherspoon Andrew , Capdevila Jaume , Glimelius Bengt , Tarazona Noelia , Begum Ruwaida , Lote Hazel , Hulkki Wilson Sanna , Mentrasti Giulia , Brown Gina , Tait Diana , Oates Jacqueline , Valeri Nicola 
Published: January 2018

AbstractThere are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.
Differential tolerance to nickel between Dreissena polymorpha and Dreissena rostriformis bugensis populations
Authors: Potet Marine , Giambérini Laure , Pain-Devin Sandrine , Louis Fanny , Bertrand Carole , Devin Simon 
Published: January 2018

AbstractDifferential tolerance to stress is partly responsible for the heterogeneity of biomarker responses between populations of a sentinel species. Although currently used for freshwater biomonitoring, studies concerning inter-populational variability in tolerance to contaminants for the zebra mussel (Dreissena polymorpha) are scarce. Moreover, this well-known invader is currently replaced by another, the quagga mussel (Dreissena rostriformis bugensis). To evaluate the differential tolerance between dreissenids, several populations of both species were exposed to a high concentration of nickel. A LT50 (time when 50% of individuals were dead) was established for each population. Biomarker responses and internal nickel concentration were also measured, to link tolerance with physiological status. Results evidenced that D. polymorpha populations are more heterogeneous and more tolerant than D. r. bugensis ones. For D. polymorpha populations only, LT50 values were positively correlated with the nickel contamination in situ, with higher anti-oxidative defences and a higher Integrated Biomarker Response value in the field. Such findings may be explained by local adaptation and invasion dynamic within each species. The significance of this differential tolerance when using biomarker responses for biomonitoring purposes is thus discussed.
Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells
Authors: Song Anping , Zhu Ling , Gorantla Gowthami , Berdysz Olimpia , Amici Stephanie A. , Guerau-de-Arellano Mireia , Madalena Kathryn M. , Lerch Jessica K. , Liu Xiaoyu , Quan Ning 
Published: January 2018

AbstractInterleukin 1 is a pleiotropic cytokine that mediates diverse functions through its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have focused on the expression and function of IL-1R1 in immune cells. Here we performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the highest sensitivity ofin situdetection of IL-1R1 mRNA and protein. Besides validating previously reported IL-1R1 expression in the endocrine tissues including pituitary and pancreas, our results refuted previously reported exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal root ganglia (DRG). Instead, IL-1R1 expression was detected in endothelial cells within DRG, spinal cord, pancreas, colon, muscles and many immune organs. In addition, gp38+fibroblastic reticular cells (FRCs), rather than tissue macrophages or other immune cells, were found to express high levels of IL-1R1 in colon and many immune organs. A functional test of spleen FRCs showed that they responded rapidly to systemic IL-1β stimulationin vivo. Taken together, this study provides a rigorous re-examination of IL-1R1 expression in peripheral tissues and reveals tissue FRCs as a previously unappreciated novel high IL-1R1-expressing cell type in peripheral IL-1 signaling.
Ultrathin silicon oxynitride layer on GaN for dangling-bond-free GaN/insulator interface
Authors: Nishio Kengo , Yayama Tomoe , Miyazaki Takehide , Taoka Noriyuki , Shimizu Mitsuaki 
Published: January 2018

AbstractDespite the scientific and technological importance of removing interface dangling bonds, even an ideal model of a dangling-bond-free interface between GaN and an insulator has not been known. The formation of an atomically thin ordered buffer layer between crystalline GaN and amorphous SiO2 would be a key to synthesize a dangling-bond-free GaN/SiO2 interface. Here, we predict that a silicon oxynitride (Si4O5N3) layer can epitaxially grow on a GaN(0001) surface without creating dangling bonds at the interface. Our ab initio calculations show that the GaN/Si4O5N3 structure is more stable than silicon-oxide-terminated GaN(0001) surfaces. The electronic properties of the GaN/Si4O5N3 structure can be tuned by modifying the chemical components near the interface. We also propose a possible approach to experimentally synthesize the GaN/Si4O5N3 structure.
Capturing expert uncertainty in spatial cumulative impact assessments
Authors: Jones Alice R. , Doubleday Zoë A. , Prowse Thomas A. A. , Wiltshire Kathryn H. , Deveney Marty R. , Ward Tim , Scrivens Sally L. , Cassey Phillip , O’Connell Laura G. , Gillanders Bronwyn M. 
Published: January 2018

AbstractUnderstanding the spatial distribution of human impacts on marine environments is necessary for maintaining healthy ecosystems and supporting ‘blue economies’. Realistic assessments of impact must consider the cumulative impacts of multiple, coincident threats and the differing vulnerabilities of ecosystems to these threats. Expert knowledge is often used to assess impact in marine ecosystems because empirical data are lacking; however, this introduces uncertainty into the results. As part of a spatial cumulative impact assessment for Spencer Gulf, South Australia, we asked experts to estimate score ranges (best-case, most-likely and worst-case), which accounted for their uncertainty about the effect of 32 threats on eight ecosystems. Expert scores were combined with data on the spatial pattern and intensity of threats to generate cumulative impact maps based on each of the three scoring scenarios, as well as simulations and maps of uncertainty. We compared our method, which explicitly accounts for the experts’ knowledge-based uncertainty, with other approaches and found that it provides smaller uncertainty bounds, leading to more constrained assessment results. Collecting these additional data on experts’ knowledge-based uncertainty provides transparency and simplifies interpretation of the outputs from spatial cumulative impact assessments, facilitating their application for sustainable resource management and conservation.
Repeated photon and C-ion irradiations in vivo have different impact on alteration of tumor characteristics
Authors: Sato Katsutoshi , Nitta Nobuhiro , Aoki Ichio , Imai Takashi , Shimokawa Takashi 
Published: January 2018

AbstractPrecise characterization of tumor recurrence and regrowth after radiotherapy are important for prognostic understanding of the therapeutic effect. Here, we established a novel in vivo mouse model for evaluating the characteristics of regrown tumor after repeated photon and carbon ion (C-ion) irradiations. The results showed that tumor growth rate, lung metastasis, shortening of the survival of the tumor-bearing mice, and tumor microvessel formation were promoted 2- to 3-fold, and expression of angiogenic and metastatic genes increased 1.5- to 15-fold in regrown tumors after repeated photon irradiations, whereas repeated C-ion irradiations did not alter these characteristics. Interestingly, both repeated photon and C-ion irradiations did not generate radioresistance, which is generally acquired for in vitro treatment. Our results demonstrated that the repetition of photon, and not C-ion, irradiations in vivo alter the characteristics of the regrown tumor, making it more aggressive without acquisition of radioresistance.
Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies
Authors: Juenemann Katrin , Jansen Anne H. P. , van Riel Luigi , Merkx Remco , Mulder Monique P. C. , An Heeseon , Statsyuk Alexander , Kirstein Janine , Ovaa Huib , Reits Eric A. 
Published: January 2018

AbstractMany neurodegenerative diseases, such as Huntington’s disease, are hallmarked by the formation of intracellular inclusion bodies (IBs) that are decorated with ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and components involved in protein quality control at IBs suggests local ubiquitin-dependent enzymatic activity. In this study, we examine recruitment of ubiquitin to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of intracellular substrates, such as mHtt, in a conjugation-dependent manner. Furthermore, we report that mHtt IBs recruit catalytically active enzymes involved in (de)-ubiquitination processes based on novel activity-based probes. However, we also find that the overexpression of the GFP-ubiquitin reporter, unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt initiated IBs.
The microRNA regulatory landscape of MSC-derived exosomes: a systems view
Authors: Ferguson Scott W. , Wang Jinli , Lee Christine J. , Liu Maixian , Neelamegham Sriram , Canty John M. , Nguyen Juliane 
Published: January 2018

AbstractMesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.
Efficient inhibition of African swine fever virus replication by CRISPR/Cas9 targeting of the viral p30 gene (CP204L)
Authors: Hübner Alexandra , Petersen Bjoern , Keil Günther M. , Niemann Heiner , Mettenleiter Thomas C. , Fuchs Walter 
Published: January 2018

AbstractAfrican swine fever is a devastating viral disease of domestic and wild pigs against which no vaccine or therapy is available. Therefore, we applied the CRISPR (clustered regularly interspaced short palindromic repeats) – Cas9 nuclease system to target the double-stranded DNA genome of African swine fever virus (ASFV). To this end, a permissive wild boar lung (WSL) cell line was modified by stable transfection with a plasmid encoding Cas9 and a guide RNA targeting codons 71 to 78 of the phosphoprotein p30 gene (CP204L) of ASFV. Due to targeted Cas9 cleavage of the virus genome, plaque formation of ASFV was completely abrogated and virus yields were reduced by four orders of magnitude. The specificity of these effects could be demonstrated by using a natural ASFV isolate and escape mutants possessing nucleotide exchanges within the target sequence, which were not inhibited in the Cas9-expressing cell line. Growth of the cell line was not affected by transgene expression which, as well as virus inhibition, proved to be stable over at least 50 passages. Thus, CRISPR-Cas9 mediated targeting of the ASFV p30 gene is a valid strategy to convey resistance against ASF infection, which may also be applied in its natural animal host.
Annual shifts of flow regime alteration: new insights from the Chaishitan Reservoir in China
Authors: Zhang Yongyong , Zhai Xiaoyan , Zhao Tongtiegang 
Published: January 2018

AbstractReservoir regulation is variable for flow regime alterations and mainly depends on operational objectives and hydro-meteorological conditions. In this study, the flow regime metrics (i.e., magnitude, variability and frequency, duration, timing and rate of change) are adopted to describe variations in both long-term inflow and outflow series of the Chaishitan Reservoir in China. Deviations between the inflow and outflow metrics are calculated to assess the flow regime alterations at annual scale. Further, dimensions of both time and flow regimes are reduced by multivariate statistical analysis, and the regulation patterns and their annual shifts are identified. Results show that: four regulation patterns are identified from 2004 to 2015. The regulation is gradually enhanced over time with typical features of different hydrological years. In dry years, the pattern is slightly regulated flow regimes with slightly discharging stored water and flattening outflow, moderate stability and intermittency. In normal years, the pattern is slightly regulated flow regimes with extremely increasing flow magnitude in the pre-nonflood season, high stability and slight intermittency. In wet years, the pattern is moderately regulated flow regimes with moderately decreasing flow magnitude in the flood season but extremely increasing flow magnitude in the nonflood season, slight stability and high intermittency.
3D virtual histology of murine kidneys –high resolution visualization of pathological alterations by micro computed tomography
Authors: Missbach-Guentner Jeannine , Pinkert-Leetsch Diana , Dullin Christian , Ufartes Roser , Hornung Daniel , Tampe Bjoern , Zeisberg Michael , Alves Frauke 
Published: January 2018

AbstractThe increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (µCT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models.
The Transmission and Evolution of HIV-1 Quasispecies within One Couple: a Follow-up Study based on Next-Generation Sequencing
Authors: Yu Fengjiao , Wen Yujie , Wang Jibao , Gong Yurong , Feng Kaidi , Ye Runhua , Jiang Yan , Zhao Qi , Pan Pinliang , Wu Hao , Duan Song , Su Bin , Qiu Maofeng 
Published: January 2018

AbstractNext-generation sequencing (NGS) has been successfully used to trace HIV-1 infection. In this study, we investigated the transmission and evolution of HIV-1 quasispecies in a couple infected through heterosexual behavior. A heterosexual couple in which both partners were infected with HIV-1 was followed up for 54 months. Blood samples including whole-blood and plasma samples, were collected at various time points. After HIV-1 subtyping, NGS (Miseq platform) was used to sequence the env region of the HIV-1 quasispecies. Genetic distances were calculated, and phylogenetic trees were generated. We found both partners were infected with HIV-1 subtype circulating recombinant form (CRF), CRF65_cpx. The quasispecies distribution was relatively tightly clustered in the phylogenetic tree during early infection. Over time, the distribution of HIV-1 quasispecies gradually became more dispersed at 12th months, with a progressive increase in gene diversity. By 37th months, the sequences obtained for both partners formed different clusters in the phylogenetic tree. These results suggest that the HIV-1 contact tracing results generated by the Miseq platform may be more reliable than other conventional sequencing methods, which can provide important information about the transmission and evolution of HIV-1. Our findings may help to better target preventative interventions for promoting public health.