bluuebunny/crossref_metadata_2025_split huggingface dataset:
A framework for tracer-based metabolism in mammalian cells by NMR
Authors: Saborano Raquel , Eraslan Zuhal , Roberts Jennie , Khanim Farhat L. , Lalor Patricia F. , Reed Michelle A. C. , Günther Ulrich L. 
Published: February 2019

AbstractMetabolism changes extensively during the normal proliferation and differentiation of mammalian cells, and in cancer and inflammatory diseases. Since changes in the metabolic network reflect interactions between genetic, epigenetic and environmental changes, it is helpful to study the flow of label from isotopically labelled precursors into other metabolites rather than static metabolite levels. For this Nuclear Magnetic Resonance (NMR) spectroscopy is an attractive technique as it can quantify site-specific label incorporation. However, for applications using human cells and cell lines, the challenge is to optimize the process to maximize sensitivity and reproducibility. Here we present a new framework to analyze metabolism in mammalian cell lines and primary cells, covering the workflow from the preparation of cells to the acquisition and analysis of NMR spectra. We have applied this new approach in hematological and liver cancer cell lines and confirm the feasibility of tracer-based metabolism in primary liver cells.
Molecular evolution of influenza B virus during 2011–2017 in Chaoyang, Beijing, suggesting the free influenza vaccine policy
Authors: Lei Na , Wang Hai-bin , Zhang Yu-song , Zhao Jian-hong , Zhong Yi , Wang Yuan-jie , Huang Li-yong , Ma Jian-xin , Sun Qiang , Yang Lei , Shu Yue-long , Li Shu-ming , Sun Ling-li 
Published: February 2019

AbstractTwo influenza B virus lineages, B/Victoria and B/Yamagata, are co-circulating in human population. While the two lineages are serologically distinct and TIV only contain one lineage. It is important to investigate the epidemiological and evolutionary dynamics of two influenza B virus lineages in Beijing after the free influenza vaccine policy from 2007. Here, we collected the nasopharyngeal swabs of 12657 outpatients of influenza-like illness and subtyped by real-time RT-PCR during 2011–2017. The HA and NA genes of influenza B were fully sequenced. The prevalence is the highest in the 6–17 years old group among people infected with influenza B. Yamagata-lineage virus evolved to two inter-clade from 2011–2014 to 2014–2017. The amino acids substitutions of HA1 region were R279K in strains of 2011–2014 and L173Q, M252V in strains of 2014–2017. Substitutions L58P, I146V were observed in HA1 region of Victoria-lineage virus in 2011–2012 and I117V, N129D were showed in 2015–2017. Phylogenetic analysis of NA showed Yamagata-Victoria inter-lineage reassortant occurred in 2013–2014. Influenza B mainly infect the school-aged children in Beijing and the free influenza vaccine inoculation does not seem to block school-age children from infection with influenza B. The antigen characteristics of circulating influenza B were different to the recommended vaccine strains. We concluded that the Victoria-lineage vaccine strain should been changed and the free influenza vaccine should be revalued.
Dynamic Effects of CYP2D6 Genetic Variants in a Set of Poor Metaboliser Patients with Infiltrating Ductal Cancer Under Treatment with Tamoxifen
Authors: Ariza Márquez Yeimy Viviana , Briceño Ignacio , Aristizábal Fabio , Niño Luis Fernando , Yosa Reyes Juvenal 
Published: February 2019

AbstractBreast cancer is a group of multigenic diseases. It is the most common cancer diagnosed among women worldwide and is often treated with tamoxifen. Tamoxifen is catalysed by cytochrome P450 2D6 (CYP2D6), and inter-individual variations in the enzyme due to single nucleotide polymorphisms (SNPs) could alter enzyme activity. We evaluated SNPs in patients from Colombia in South America who were receiving tamoxifen treatment for breast cancer. Allelic diversity in the CYP2D6 gene was found in the studied population, with two patients displaying the poor-metaboliser phenotype. Molecular dynamics and trajectory analyses were performed for CYP2D6 from these two patients, comparing it with the common allelic form (CYP2D6*1). Although we found no significant structural change in the protein, its dynamics differ significantly from those of CYP2D6*1, the effect of such differential dynamics resulting in an inefficient enzyme with serious implications for tamoxifen-treated patients, increasing the risk of disease relapse and ineffective treatment.
Translocation of promoter-conserved hatching enzyme genes with intron-loss provides a new insight in the role of retrocopy during teleostean evolution
Authors: Nagasawa Tatsuki , Kawaguchi Mari , Yano Tohru , Isoyama Sho , Yasumasu Shigeki , Okabe Masataka 
Published: February 2019

AbstractThe hatcing enzyme gene (HE) encodes a protease that is indispensable for the hatching process and is conserved during vertebrate evolution. During teleostean evolution, it is known that HE experienced a drastic transfiguration of gene structure, namely, losing all of its introns. However, these facts are contradiction with each other, since intron-less genes typically lose their original promoter because of duplication via mature mRNA, called retrocopy. Here, using a comparative genomic assay, we showed that HEs have changed their genomic location several times, with the evolutionary timings of these translocations being identical to those of intron-loss. We further showed that HEs maintain the promoter sequence upstream of them after translocation. Therefore, teleostean HEs are unique genes which have changed intra- (exon-intron) and extra-genomic structure (genomic loci) several times, although their indispensability for the reproductive process of hatching implies that HE genes are translocated by retrocopy with their promoter sequence.
Optimal design, anti-tumour efficacy and tolerability of anti-CXCR4 antibody drug conjugates
Authors: Costa Maria José , Kudaravalli Jyothirmayee , Ma Jing-Tyan , Ho Wei-Hsien , Delaria Kathy , Holz Charles , Stauffer Angela , Chunyk Allison Given , Zong Qing , Blasi Eileen , Buetow Bernard , Tran Thomas-Toan , Lindquist Kevin , Dorywalska Magdalena , Rajpal Arvind , Shelton David L. , Strop Pavel , Liu Shu-Hui 
Published: February 2019

AbstractAntibody-drug conjugates (ADCs) are promising therapies for haematological cancers. Historically, their therapeutic benefit is due to ADC targeting of lineage-restricted antigens. TheC-X-Cmotif chemokinereceptor 4 (CXCR4) is attractive for targeted therapy of haematological cancers, given its expression in multiple tumour types and role in cancer “homing” to bone marrow. However, CXCR4 is also expressed in haematopoietic cells and other normal tissues, raising safety challenges to the development of anti-CXCR4 ADCs for cancer treatment. Here, we designed the first anti-CXCR4 ADC with favourable therapeutic index, effective in xenografts of haematopoietic cancers resistant to standard of care and anti-CXCR4 antibodies. We screened multiple ADC configurations, by varying type of linker-payload, drug-to-antibody ratio (DAR), affinity and Fc format. The optimal ADC bears a non-cleavable linker, auristatin as payload at DAR = 4 and a low affinity antibody with effector–reduced Fc. Contrary to other drugs targeting CXCR4, anti-CXCR4 ADCs effectively eliminated cancer cells as monotherapy, while minimizing leucocytosis. The optimal ADC selectively eliminated CXCR4+cancer cells in solid tumours, but showed limited toxicity to normal CXCR4+tissues, sparing haematopoietic stem cells and progenitors. Our work provides proof-of-concept that through empirical ADC design, it is possible to target proteins with broad normal tissue expression.
Discovery of ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ureidyl derivatives as selective non-steroidal agonists of the G-protein coupled bile acid receptor-1
Authors: Di Leva Francesco Saverio , Festa Carmen , Carino Adriana , De Marino Simona , Marchianò Silvia , Di Marino Daniele , Finamore Claudia , Monti Maria Chiara , Zampella Angela , Fiorucci Stefano , Limongelli Vittorio 
Published: February 2019

AbstractThe G-protein bile acid receptor 1 (GPBAR1) has emerged in the last decade as prominent target for the treatment of metabolic and inflammatory diseases including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. To date numerous bile acid derivatives have been identified as GPBAR1 agonists, however their clinical application is hampered by the lack of selectivity toward the other bile acid receptors. Therefore, non-steroidal GPBAR1 ligands able to selectively activate the receptor are urgently needed. With this aim, we here designed, synthesized and biologically evaluated ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl) urea derivatives as novel potent GPBAR1 agonists. Particularly, compounds 9 and 10 induce the mRNA expression of the GPBAR1 target gene pro-glucagon and show high selectivity over the other bile acid receptors FXR, LXRα, LXRβ and PXR, and the related receptors PPARα and PPARγ. Computational studies elucidated the binding mode of 10 to GPBAR1, providing important structural insights for the design of non-steroidal GPBAR1 agonists. The pharmacokinetic properties of 9 and 10 suggest that the ((1,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ureydil scaffold might be exploited to achieve effective drug candidates to treat GPBAR1 related disorders.
Slight changes in the chemical structure of haemanthamine greatly influence the effect of the derivatives on rumen fermentation in vitro
Authors: Ramos-Morales Eva , Tibble-Howlings Jamie , Lyons Laura , Ogbu Magnus O. , Murphy Patrick J. , Braganca Radek , Newbold Charles James 
Published: February 2019

AbstractAlthough the potential of plants extracts to improve feed efficiency and animal productivity and decrease methane emissions by enteric fermentation has been shown, the information available is often contradictory which has been attributed to differences in the complex mixture of bioactive compounds and their interactions. Understanding the degree to which structural features in a compound may affect the biological activity of an extract is essential. We hypothesised that relative small variations in the structure of a compound can have a significant influence on the ability of the derivatives to alter fermentation in the rumen. Nine compounds were synthetized from the natural alkaloid haemanthamine and tested in vitro for their effects on rumen protozoa and fermentation parameters. Our results showed that simple esterifications of haemanthamine or its derivative dihydrohaemanthamine with acetate, butyrate, pivalate or hexanoate led to compounds that differed in their effects on rumen fermentation.
Impact of sarcopenia in patients with advanced non–small cell lung cancer treated with PD-1 inhibitors: A preliminary retrospective study
Authors: Shiroyama Takayuki , Nagatomo Izumi , Koyama Shohei , Hirata Haruhiko , Nishida Sumiyuki , Miyake Kotaro , Fukushima Kiyoharu , Shirai Yuya , Mitsui Yuichi , Takata So , Masuhiro Kentaro , Yaga Moto , Iwahori Kota , Takeda Yoshito , Kida Hiroshi , Kumanogoh Atsushi 
Published: February 2019

AbstractThe aim of this study was to investigate the clinical impact of sarcopenia on the efficacy of programmed death (PD)-1 inhibitors. We retrospectively reviewed the medical records of all patients treated with nivolumab or pembrolizumab between January 2016 and September 2018 for previously treated advanced non–small cell lung cancer (NSCLC). The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on baseline computed tomography was assessed to calculate the psoas muscle index (PMI). Sarcopenia was defined based on PMI cut-off values for Asian adults (6.36 cm2/m2 for males and 3.92 cm2/m2 for females). A total of 42 patients were analysed. The prevalence of sarcopenia was 52.4%. Sarcopenia was significantly associated with poorer progression-free survival (PFS) (median, 2.1 vs. 6.8 months, p = 0.004). Compared to patients with sarcopenia, those without sarcopenia had a higher overall response rate (40.0% vs. 9.1%, p = 0.025) and 1-year PFS rate (38.1% vs. 10.1%). In conclusion, sarcopenia at baseline as determined using computed tomography is a significant predictor of worse outcome in patients with advanced NSCLC receiving PD-1 blockade. Screening for sarcopenia may help identify patients more likely to achieve a long-term response in routine clinical practice.
Ground–state structure of semiconducting and superconducting phases in xenon carbides at high pressure
Authors: Bovornratanaraks Thiti , Tsuppayakorn-aek Prutthipong , Luo Wei , Ahuja Rajeev 
Published: February 2019

AbstractThe ‘missing Xe paradox’ is one of the phenomena at the Earth’s atmosphere. Studying the ‘missing Xe paradox’ will provide insights into a chemical reaction of Xe with C. We search the ground–state structure candidates of xenon carbides using the Universal Structure Predictor: Evolutionary Xtallography (USPEX) code, which has been successfully applied to a variety of systems. We predict that XeC2 is the most stable among the convex hull. We find that the I$$\bar{4}$$

4
¯

2m structure of XeC2 is the semiconducting phase. Accurate electronic structures of tetragonal XeC2 have been calculated using a hybrid density functionals HSE06, which gives larger more accurate band gap than a GGA–PBE exchange-correlation functional. Specifically, we find that the I$$\bar{4}$$

4
¯

2m structure of XeC2 is a dynamically stable structure at high pressure. We also predict that the P6/mmm structure of XeC2 is the superconducting phase with a critical temperature of 38 K at 200 GPa. The ground-state structure of xenon carbides is of critical importance for understanding in the missing Xe. We discuss the inference of the stable structures of XeC2. The accumulation of electrons between Xe and C led to the stability by investigating electron localization function (ELF).
A non-persistent aphid-transmitted Potyvirus differentially alters the vector and non-vector biology through host plant quality manipulation
Authors: Gadhave Kiran R. , Dutta Bhabesh , Coolong Timothy , Srinivasan Rajagopalbabu 
Published: February 2019

AbstractThe association of plant viruses with their vectors has significant implications for virus transmission and spread. Only a few studies, with even fewer pathosystems, have explored non-persistent (NP) virus-vector interactions that are presumed to be transient. We studied how a NP virus, Papaya ringspot virus (PRSV) influenced the behavior and biology of its vector, the melon aphid (Aphis gossypii Glover) and the non-vector, silverleaf whitefly (Bemisia tabaci Gennadius). We also assessed whether the fitness effects on aphids are modulated through changes in the host plant, squash (Cucurbita pepo L.) nutrient profile. The overall performance of A. gossypii was substantially higher on PRSV-infected plants, along with increased arrestment on PRSV-infected than non-infected plants. No such PRSV-modulated fitness effects were observed with B. tabaci. PRSV-infected plants had increased concentrations of free essential amino acids: threonine, arginine and lysine; non-essential amino acids: glycine and homocysteine; and soluble carbohydrates: galactose, raffinose and cellobiose. In general, PRSV encouraged long-term feeding and enhanced fitness of A. gossypii through host plant nutrient enrichment. These findings provide evidence for a NP virus mediated positive fitness effects on its vector, with no spillover fitness benefits to the non-vector within the same feeding guild.
16S rRNA amplicon sequencing characterization of caecal microbiome composition of broilers and free-range slow-growing chickens throughout their productive lifespan
Authors: Ocejo Medelin , Oporto Beatriz , Hurtado Ana 
Published: February 2019

AbstractGut microbiota affects health, metabolism and immunity of the host, and in the case of livestock, also food-safety. Here, 16S rRNA gene high-throughput Illumina sequencing was used to describe the microbiome of chicken caeca in two different breeds and management systems throughout their whole productive lifespan. Broilers (Ross-308), as a fast-growing breed reared in an intensive system for 42-days, and a slow-growing breed of chicken (Sasso-T451A) reared in an extensive farming system with outdoor access for 86-days, were compared. The core microbiome and differentially abundant taxa, as well as taxa associated with age were identified. Age was identified as the strongest influencing factor in caecal microbiota composition, and, in general, each age-group showed an age-associated community profile, with a transition period at the middle of their lifespan. However, substantial differences were observed in the composition of caecal microbiota of both chicken breeds, microbiota being richer and more complex in free-range chicken than in broilers. Several taxa positively/negatively correlated with Campylobacter relative abundance were also identified. Especially noteworthy was the identification by microbial community comparison of microbiota profiles suggestive of dysbiosis in several free-range chickens, probably associated to the typhlitis observed in the lumen of their caeca.
Current channeling along extended defects during electroreduction of SrTiO3
Authors: Rodenbücher Christian , Menzel Stephan , Wrana Dominik , Gensch Thomas , Korte Carsten , Krok Franciszek , Szot Krzysztof 
Published: February 2019

AbstractElectroreduction experiments on metal oxides are well established for investigating the nature of the material change in memresistive devices, whose basic working principle is an electrically-induced reduction. While numerous research studies on this topic have been conducted, the influence of extended defects such as dislocations has not been addressed in detail hitherto. Here, we show by employing thermal microscopy to detect local Joule heating effects in the first stage of electroreduction of SrTiO3 that the current is channelled along extended defects such as dislocations which were introduced mechanically by scratching or sawing. After prolonged degradation, the matrix of the crystal is also electroreduced and the influence of the initially present dislocations diminished. At this stage, a hotspot at the anode develops due to stoichiometry polarisation leading not only to the gliding of existing dislocations, but also to the evolution of new dislocations. Such a formation is caused by electrical and thermal stress showing dislocations may play a significant role in resistive switching effects.
Thermogenesis-independent metabolic benefits conferred by isocaloric intermittent fasting in ob/ob mice
Authors: Kim Yun Hye , Lee Ju Hee , Yeung Joanna Lan-Hing , Das Eashita , Kim Ri Youn , Jiang Yanqing , Moon Joon Ho , Jeong Hyerin , Thakkar Nikita , Son Joe Eun , Trzaskalski Natasha , Hui Chi-chung , Doh Kyung-Oh , Mulvihill Erin E. , Kim Jae-Ryong , Kim Kyoung-Han , Sung Hoon-Ki 
Published: February 2019

AbstractIntermittent fasting (IF) is an effective dietary intervention to counteract obesity-associated metabolic abnormalities. Previously, we and others have highlighted white adipose tissue (WAT) browning as the main underlying mechanism of IF-mediated metabolic benefits. However, whether IF retains its efficacy in different models, such as genetically obese/diabetic animals, is unknown. Here, leptin-deficient ob/ob mice were subjected to 16 weeks of isocaloric IF, and comprehensive metabolic phenotyping was conducted to assess the metabolic effects of IF. Unlike our previous study, isocaloric IF-subjected ob/ob animals failed to exhibit reduced body weight gain, lower fat mass, or decreased liver lipid accumulation. Moreover, isocaloric IF did not result in increased thermogenesis nor induce WAT browning in ob/ob mice. These findings indicate that isocaloric IF may not be an effective approach for regulating body weight in ob/ob animals, posing the possible limitations of IF to treat obesity. However, despite the lack of improvement in insulin sensitivity, isocaloric IF-subjected ob/ob animals displayed improved glucose tolerance as well as higher postprandial insulin level, with elevated incretin expression, suggesting that isocaloric IF is effective in improving nutrient-stimulated insulin secretion. Together, this study uncovers the insulinotropic effect of isocaloric IF, independent of adipose thermogenesis, which is potentially complementary for the treatment of type 2 diabetes.
Visual dependency and postural control on swing performance in golf players
Authors: Micarelli Alessandro , Viziano Andrea , Lanzillotta Alessia , Ruscello Bruno , D'Ottavio Stefano , Alessandrini Marco 
Published: February 2019

AbstractIndividuals have to reweight the respective contribution of the different sources of sensorial information for regulating posture and balance, especially during fine task execution. Given the evidences indicating strategy during swing performance as associated with prioritization of task‐relevant visuospatial information for skill execution, the aim of the present work is to assess differences in visual dependency (VD) and postural control in a population of expert (EXP) and non‐expert (NEXP) golfers when compared with healthy subjects (HC) and to discover possible relationships between these outcomes and swing performance. Thus, 15 golfers (EXP = 7; NEXP = 8) and 32 matched HC underwent otoneurological testing including video Head Impulse Test, posturography and Rod and Disk Test (RDT). Golf players also underwent a swing session procedure, which performance was measured by means of the Flightscope X2 Doppler‐radar launch monitor system. EXP subjects demonstrated significant (p < 0.05) lower values in i) counter‐clockwise (CCW) and clockwise (CW) dynamic conditions when compared with both NEXP and HC subjects RDT outcome measures and ii) surface and length posturography values as compared with HC subjects. When treating golf players outcomes as ‘a continuum’, CCW and CW scores were found to positively correlate with both lateral distance and horizontal launch angle and to negatively correlate with spin rpm. In conclusion, the present study suggests that the high‐level of visual‐independency demonstrated by EXP subjects may be functionally related in expert golfers to an effective motor strategy preferentially not referring to an inappropriate reliance on visual input.
Artistic Crimes and Misdemeanours
Authors: Davies David 
Published: February 2019

Abstract
Denis Dutton claimed that, to grasp why it matters to the artistic value of a painting like The Disciples at Emmaus that it was painted by van Meegeren in the first half of the twentieth century rather than by Vermeer in the seventeenth century, we need to locate what van Meegeren did in a wider class of ‘artistic crimes’ involving ‘misrepresented artistic performances’. I begin by clarifying how the notions of ‘artistic performance’ and ‘misrepresentation’ are to be understood in the context of Dutton’s paper. I survey a range of examples of misrepresented artistic performances in Dutton’s sense, and ask when they involve ‘artistic crimes’. I then seek a principled way of justifying what seem to be our clear intuitions—apparent in our artistic practice—as to which ‘misrepresented artistic performances’ are artistic crimes and which are not.
Epidemiology: Back to the Future
Authors: Olshan Andrew F , Diez Roux Ana V , Hatch Maureen , Klebanoff Mark A 
Published: February 2019

Abstract
In 2018, the Society for Epidemiologic Research and its partner journal, the American Journal of Epidemiology, assembled a working group to develop a set of papers devoted to the “future of epidemiology.” These 14 papers covered a wide range of topic areas and perspectives, from thoughts on our profession, teaching, and methods to critical areas of substantive research. The authors of those papers considered current challenges and future opportunities for research and education. In light of past commentaries, 4 papers also include reflections on the discipline at present and in the future.