bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukaemia
Authors: Gu Zhaohui , Churchman Michelle , Roberts Kathryn , Li Yongjin , Liu Yu , Harvey Richard C. , McCastlain Kelly , Reshmi Shalini C. , Payne-Turner Debbie , Iacobucci Ilaria , Shao Ying , Chen I-Ming , Valentine Marcus , Pei Deqing , Mungall Karen L. , Mungall Andrew J. , Ma Yussanne , Moore Richard , Marra Marco , Stonerock Eileen , Gastier-Foster Julie M. , Devidas Meenakshi , Dai Yunfeng , Wood Brent , Borowitz Michael , Larsen Eric E. , Maloney Kelly , Mattano Jr Leonard A. , Angiolillo Anne , Salzer Wanda L. , Burke Michael J. , Gianni Francesca , Spinelli Orietta , Radich Jerald P. , Minden Mark D. , Moorman Anthony V. , Patel Bella , Fielding Adele K. , Rowe Jacob M. , Luger Selina M. , Bhatia Ravi , Aldoss Ibrahim , Forman Stephen J. , Kohlschmidt Jessica , Mrózek Krzysztof , Marcucci Guido , Bloomfield Clara D. , Stock Wendy , Kornblau Steven , Kantarjian Hagop M. , Konopleva Marina , Paietta Elisabeth , Willman Cheryl L. , L. Loh Mignon , P. Hunger Stephen , Mullighan Charles G. 
Published: November 2016

AbstractChromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements betweenMEF2D(myocyte enhancer factor 2D) and five genes (BCL9,CSF1R,DAZAP1,HNRNPUL1andSS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which isMEF2D-BCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases withMEF2Drearrangements, which include an additional fusion partner,FOXJ2; thus,MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations.MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation ofHDAC9expression and sensitive to histone deacetylase inhibitor treatment. Thus,MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.
Recent pause in the growth rate of atmospheric CO2 due to enhanced terrestrial carbon uptake
Authors: Keenan Trevor F , Prentice I. Colin , Canadell Josep G , Williams Christopher A , Wang Han , Raupach Michael , Collatz G. James 
Published: November 2016

AbstractTerrestrial ecosystems play a significant role in the global carbon cycle and offset a large fraction of anthropogenic CO2 emissions. The terrestrial carbon sink is increasing, yet the mechanisms responsible for its enhancement, and implications for the growth rate of atmospheric CO2, remain unclear. Here using global carbon budget estimates, ground, atmospheric and satellite observations, and multiple global vegetation models, we report a recent pause in the growth rate of atmospheric CO2, and a decline in the fraction of anthropogenic emissions that remain in the atmosphere, despite increasing anthropogenic emissions. We attribute the observed decline to increases in the terrestrial sink during the past decade, associated with the effects of rising atmospheric CO2 on vegetation and the slowdown in the rate of warming on global respiration. The pause in the atmospheric CO2 growth rate provides further evidence of the roles of CO2 fertilization and warming-induced respiration, and highlights the need to protect both existing carbon stocks and regions, where the sink is growing rapidly.
The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis
Authors: Geng Shuo , Chen Keqiang , Yuan Ruoxi , Peng Liang , Maitra Urmila , Diao Na , Chen Chun , Zhang Yao , Hu Yuan , Qi Chen-Feng , Pierce Susan , Ling Wenhua , Xiong Huabao , Li Liwu 
Published: November 2016

AbstractSustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.
Biologically based neural circuit modelling for the study of fear learning and extinction
Authors: Nair Satish S , Paré Denis , Vicentic Aleksandra 
Published: November 2016

AbstractThe neuronal systems that promote protective defensive behaviours have been studied extensively using Pavlovian conditioning. In this paradigm, an initially neutral-conditioned stimulus is paired with an aversive unconditioned stimulus leading the subjects to display behavioural signs of fear. Decades of research into the neural bases of this simple behavioural paradigm uncovered that the amygdala, a complex structure comprised of several interconnected nuclei, is an essential part of the neural circuits required for the acquisition, consolidation and expression of fear memory. However, emerging evidence from the confluence of electrophysiological, tract tracing, imaging, molecular, optogenetic and chemogenetic methodologies, reveals that fear learning is mediated by multiple connections between several amygdala nuclei and their distributed targets, dynamical changes in plasticity in local circuit elements as well as neuromodulatory mechanisms that promote synaptic plasticity. To uncover these complex relations and analyse multi-modal data sets acquired from these studies, we argue that biologically realistic computational modelling, in conjunction with experiments, offers an opportunity to advance our understanding of the neural circuit mechanisms of fear learning and to address how their dysfunction may lead to maladaptive fear responses in mental disorders.
Cost-effectiveness Analysis of Fluorouracil, Leucovorin, and Irinotecan versus Epirubicin, Cisplatin, and Capecitabine in Patients with Advanced Gastric Adenocarcinoma
Authors: Wen Feng , Zheng Hanrui , Wu Yifan , Wheeler John , Zeng Xiaoxi , Fu Ping , Li Qiu 
Published: November 2016

AbstractNo standard treatment has been accepted widely for the first-/second-line therapy for advanced gastric cancer (AGC). The current study aimed to determine a preferred strategy between FOLFIRI (fluorouracil, leucovorin, and irinotecan) and ECX (epirubicin, cisplatin,and capecitabine) for AGC from the cost-effectiveness perspective. According to a French intergroup study, two groups (ECX arm and FOLFIRI arm) and three health states (progression-free survival (PFS), progressive disease (PD) and death) were analyzed in the current Markov model. All the medical costs were calculated from a Chinese societal perspective. Although FOLFIRI was an acceptable first-line therapy in the treatment of AGC with a better time-to treatment failure (TTF) compared to ECX, ECX arm (ECX followed by FOLFIRI) gained 0.08 quality-adjusted life months (QALMs) more effectiveness benefit compared with FOLFIRI arm (FOLFIRI followed by ECX). Additionally, a lower cost was found in ECX arm ($23,813.13 versus $24,983.70). Hence, the strategy of FOLFIRI arm is dominated by ECX arm ($4,125.8 per QALM in FOLIRI arm; $3,879.724 per QALM in ECX arm). ECX followed by FOLFIRI was a preferred strategy with more effectiveness and lower cost compared with FOLFIRI followed by ECX for the treatment of AGC.
Normal incidence filters using symmetry-protected modes in dielectric subwavelength gratings
Authors: Cui Xuan , Tian Hao , Du Yan , Shi Guang , Zhou Zhongxiang 
Published: November 2016

AbstractWe investigate narrowband transmission filters based on subwavelength-grating reflectors at normal incidence. Computational results show that the filtering is realized through symmetry-protected mode coupling. The guided mode resonances introduced by the slab layer allow flexible control of the filter frequencies. The quality factor of the filters could exceed 106. Dielectric gratings can be used over the entire range of electromagnetic waves, owing to their scale-invariant operations. Owing to the high refraction index and low index dispersion of semiconductors in the infrared range, these filters can be applied over a broad range from near infrared to terahertz frequencies.
Sensitive responders among bacterial and fungal microbiome to pyrogenic organic matter (biochar) addition differed greatly between rhizosphere and bulk soils
Authors: Dai Zhongmin , Hu Jiajie , Xu Xingkun , Zhang Lujun , Brookes Philip C. , He Yan , Xu Jianming 
Published: November 2016

AbstractSensitive responses among bacterial and fungal communities to pyrogenic organic matter (PyOM) (biochar) addition in rhizosphere and bulk soils are poorly understood. We conducted a pot experiment with manure and straw PyOMs added to an acidic paddy soil, and identified the sensitive “responders” whose relative abundance was significantly increased/decreased among the whole microbial community following PyOM addition. Results showed that PyOMs significantly (p < 0.05) increased root growth, and simultaneously changed soil chemical parameters by decreasing soil acidity and increasing biogenic resource. PyOM-induced acidity and biogenic resource co-determined bacterial responder community structure whereas biogenic resource was the dominant parameter structuring fungal responder community. Both number and proportion of responders in rhizosphere soil was larger than in bulk soil, regardless of PyOM types and microbial domains, indicating the microbial community in rhizosphere soil was sensitive to PyOM addition than bulk soil. The significant increased root biomass and length caused by PyOM addition, associated with physiological processes, e.g. C exudates secretion, likely favored more sensitive responders in rhizosphere soil than in bulk soil. Our study identified the responders at fine taxonomic resolution in PyOM amended soils, improved the understanding of their ecological phenomena associated with PyOM addition, and examined their interactions with plant roots.
Evolution of Mass Movements near Epicentre of Wenchuan Earthquake, the First Eight Years
Authors: Zhang Shuai , Zhang Limin , Lacasse Suzanne , Nadim Farrokh 
Published: November 2016

AbstractIt is increasingly clear that landslides represent a major cause of economic costs and deaths in earthquakes in mountains. In the Wenchuan earthquake case, post-seismic cascading landslides continue to represent a major problem eight years on. Failure to anticipate the impact of cascading landslides could lead to unexpected losses of human lives and properties. Previous studies tended to focus on separate landslide processes, with little attention paid to the quantification of long-term evolution of multiple processes or the evolution of mass movements. The very active mass movements near the epicentre of the Wenchuan earthquake provided us a unique opportunity to understand the complex processes of the evolving cascading landslides after a strong earthquake. This study budgets the mass movements on the hillslopes and in the channels in the first eight years since the Wenchuan earthquake and verify a conservation in mass movements. A system illustrating the evolution and interactions of mass movement after a strong earthquake is proposed.
Superparamagnetic Fe3O4-PEG2K-FA@Ce6 Nanoprobes for in Vivo Dual-mode Imaging and Targeted Photodynamic Therapy
Authors: Yin Ting , Huang Peng , Gao Guo , Shapter Joseph G. , Shen Yulan , Sun Rongjin , Yue Caixia , Zhang Chunlei , Liu Yanlei , Zhou Sui , Cui Daxiang 
Published: November 2016

AbstractThe development of targeted nanoprobes is a promising approach to cancer diagnostics and therapy. In the present work, a novel multifunctional photo/magnet-diagnostic nanoprobe (MNPs-PEG2K-FA@Ce6) has been developed. This nanoprobe is built using folic acid (FA), bifunctional polyethylene glycol (PEG2K) and photosensitizer chlorin e6 (Ce6). The MNPs-PEG2K-FA@Ce6 nanoprobes are superparamagnetic, can be synthesized on a large scale by a one-pot hydrothermal process without further surface modification and are stable in an aqueous environment for eight months. Compared with free Ce6 nanoprobes in vitro studies, the MNPs-PEG2K-FA@Ce6 nanoprobes significantly enhance cellular uptake efficiency and promote the effectiveness of photodynamic therapy (PDT) with the assistance of 633 nm laser irradiation. The unique nanoprobes show superior penetration and a retention time of more than six days with less accumulation in the liver allowing highly effective tumor recognition and monitoring. Additionally, there was little damage to healthy organs or tissues. These exciting new nanoprobes could be potential building blocks to develop new clinical therapies and translational medicine.
Systematic Analysis of Drug Targets Confirms Expression in Disease-Relevant Tissues
Authors: Kumar Vinod , Sanseau Philippe , Simola Daniel F. , Hurle Mark R. , Agarwal Pankaj 
Published: November 2016

AbstractIt is commonly assumed that drug targets are expressed in tissues relevant to their indicated diseases, even under normal conditions. While multiple anecdotal cases support this hypothesis, a comprehensive study has not been performed to verify it. We conducted a systematic analysis to assess gene and protein expression for all targets of marketed and phase III drugs across a diverse collection of normal human tissues. For 87% of gene-disease pairs, the target is expressed in a disease-affected tissue under healthy conditions. This result validates the importance of confirming expression of a novel drug target in an appropriate tissue for each disease indication and strengthens previous findings showing that targets of efficacious drugs should be expressed in relevant tissues under normal conditions. Further characterization of the remaining 13% of gene-disease pairs revealed that most genes are expressed in a different tissue linked to another disease. Our analysis demonstrates the value of extensive tissue specific expression resources.both in terms of tissue and cell diversity as well as techniques used to measure gene expression.
Lycium barbarum polysaccharide attenuates high-fat diet-induced hepatic steatosis by up-regulating SIRT1 expression and deacetylase activity
Authors: Jia Li , Li Wang , Li Jianning , Li Yan , Song Hui , Luan Yansong , Qi Hui , Ma Lirong , Lu Xiaohong , Yang Yi 
Published: November 2016

AbstractIn this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD+/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling. We also found that LBP increases acetyl-CoA carboxylase (ACC) phosphorylation and adipose triglyceride lipase (ATGL) protein expression and decreases fatty acid synthase (FAS) by activating the SIRT1/LKB1/AMPK pathway in vitro and in vivo. However, SIRT1 small interfering RNA (siRNA)-mediated knockdown reversed the LBP-mediated effects on ACC, FAS and ATGL. Moreover, LBP elevated carnitine palmitoyltransferase-1 alpha (CPT-1α) expression by suppressing malonyl-CoA accumulation. Taken together, our data indicate that LBP plays a vital role in the regulation of hepatic lipid metabolism and that pharmacological activation of SIRT1 by LBP may be a strategy for the prevention of NAFLD.
The nucleolar protein GLTSCR2 is required for efficient viral replication
Authors: Wang Peng , Meng Wen , Han Shi-Chong , Li Cui-Cui , Wang Xiao-Jun , Wang Xiao-Jia 
Published: November 2016

AbstractGlioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β. Blocking cytoplasmic translocation of GLTSCR2, by deletion of its nuclear export sequence (NES), abrogated its ability to attenuate IFN-β and support viral replication. GLTSCR2-mediated attenuation of RIG-I and IFN-β led to alleviation of host cell innate immune response to viral infection. Our findings suggested that GLTSCR2 contributed to efficient viral replication, and GLTSCR2 should be considered as a potential target for therapeutic control of viral infection.
Lake Ontario salmon (Salmo salar) were not migratory: A long-standing historical debate solved through stable isotope analysis
Authors: Guiry Eric J. , Needs-Howarth Suzanne , Friedland Kevin D. , Hawkins Alicia L. , Szpak Paul , Macdonald Rebecca , Courtemanche Michelle , Holm Erling , Richards Michael P. 
Published: November 2016

AbstractLake Ontario once supported a large complex of Atlantic Salmon (Salmo salar) populations that became extinct prior to scientific study. Since the 1860s, research efforts to conserve and reintroduce a sustainable population of Atlantic Salmon have focused on determining whether Lake Ontario’s original salmon populations had migrated to the Atlantic Ocean as part of their lifecycle (anadromy), stayed in the lake year-round (potamodromy), or both. We used stable carbon, nitrogen, and sulfur isotope analyses of archaeological bones and historical museum-archived salmon scales to show that the original salmon populations from Lake Ontario completed their entire lifecycle without migrating to the Atlantic Ocean. With a time depth of more than 500 years, our findings provide a unique baseline with significant potential for informing modern restocking and conservation efforts.
27 years of benthic and coral community dynamics on turbid, highly urbanised reefs off Singapore
Authors: Guest J. R. , Tun K. , Low J. , Vergés A. , Marzinelli E. M. , Campbell A. H. , Bauman A. G. , Feary D. A. , Chou L. M. , Steinberg P. D. 
Published: November 2016

AbstractCoral cover on reefs is declining globally due to coastal development, overfishing and climate change. Reefs isolated from direct human influence can recover from natural acute disturbances, but little is known about long term recovery of reefs experiencing chronic human disturbances. Here we investigate responses to acute bleaching disturbances on turbid reefs off Singapore, at two depths over a period of 27 years. Coral cover declined and there were marked changes in coral and benthic community structure during the first decade of monitoring at both depths. At shallower reef crest sites (3–4 m), benthic community structure recovered towards pre-disturbance states within a decade. In contrast, there was a net decline in coral cover and continuing shifts in community structure at deeper reef slope sites (6–7 m). There was no evidence of phase shifts to macroalgal dominance but coral habitats at deeper sites were replaced by unstable substrata such as fine sediments and rubble. The persistence of coral dominance at chronically disturbed shallow sites is likely due to an abundance of coral taxa which are tolerant to environmental stress. In addition, high turbidity may interact antagonistically with other disturbances to reduce the impact of thermal stress and limit macroalgal growth rates.
MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways
Authors: Tang Weitao , Dong Kuiran , Li Kai , Dong Rui , Zheng Shan 
Published: November 2016

AbstractThe purpose of this study was to investigate the differential expression and functional roles of long non-coding RNAs (lncRNAs) in neuroblastoma tissue. LncRNA microarrays were used to identify differentially expressed lncRNAs between tumor and para-tumor tissues. In total, in tumor tissues, 3,098 and 1,704 lncRNAs were upregulated and downregulated, respectively. HCN3 and linc01105 exhibited the higher expression (P < 0.05; P < 0.01, respectively) in neuroblastoma tissue, whereas MEG3 displayed the lower expression (P < 0.01). HIF-1α expression was negatively correlated with cell proliferation in the linc01105 KD group. In addition, Noxa and Bid expression was positively correlated with cell apoptosis. Moreover, linc01105 knockdown promoted cell proliferation, whereas MEG3 overexpression inhibited proliferation. Finally, linc01105 knockdown, MEG3 overexpression and HCN3 knockdown all increased apoptosis. The correlation coefficients between those three lncRNAs and the International Neuroblastoma Staging System (INSS) stage were −0.48, −0.58 and −0.55, respectively. In conclusion, we have identified lncRNAs that are differentially expressed in neuroblastoma tissues. The lncRNAs HCN3, linc01105, and MEG3 may be important in biological behaviors of neuroblastoma through mechanisms involving p53 pathway members such as HIF-1α, Noxa, and Bid. The expressions of MEG3, HCN3 and linc01105 are all negatively correlated with the INSS stage.
Serological diagnosis of pneumocystosis: production of a synthetic recombinant antigen for immunodetection of Pneumocystis jirovecii
Authors: Tomás A. L. , Cardoso F. , Esteves F. , Matos O. 
Published: November 2016

AbstractDiagnosis of Pneumocystis pneumonia (PcP) relies on the detection of P. jirovecii in respiratory specimens obtained by invasive techniques. Thus, the development of a serological test is urgently needed as it will allow the diagnosis of PcP using blood, an inexpensive and non-invasive specimen. This study aims to combine the production of a multi-epitope synthetic recombinant antigen (RSA) and an ELISA test for detection of anti-P. jirovecii antibodies, in order to develop a new approach for PcP diagnosis. The RSA was selected and designed based on the study of the immunogenicity of the carboxyl-terminal domain of the major surface glycoprotein. This antigen was purified and used as an antigenic tool in an ELISA technique for detection of Ig, IgG and IgM antibodies anti-P. jirovecii (patent-pending no. PT109078). Serum specimens from 88 patients previously categorized in distinct clinical subgroups and 17 blood donors, were analysed. The IgM anti-P. jirovecii levels were statistically increased in patients with PcP (p = 0.001) and the ELISA IgM anti-P. jirovecii test presented a sensitivity of 100% and a specificity of 80.8%, when associated with the clinical diagnosis criteria. This innovative approach, provides good insights about what can be done in the future serum testing for PcP diagnosis.