bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term impact of Amazon river runoff on northern hemispheric climate
Authors: Jahfer S. , Vinayachandran P. N. , Nanjundiah Ravi S. 
Published: September 2017

AbstractAmazon discharges a large volume of freshwater into the ocean, yet its impact on climate is largely unknown. Climate projections show that a warmer northern tropical Atlantic Ocean together with a warmer equatorial Pacific lead to extreme droughts in the Amazonia, considerably reducing the Amazon runoff. Here we present results from coupled model simulations and observations on the climatic response to a significant reduction in Amazon runoff into the Atlantic Ocean. Climate model simulation without Amazon runoff resulted in cooler equatorial Atlantic, weakening the Hadley cell and thereby the atmospheric meridional cells. Consequently, the extratropical westerlies turned weaker, leading to prevalent negative North Atlantic Oscillation (NAO) like climate, similar to the observed anomalies during Amazon drought years. This study reaffirms that spatial signature of NAO is in part driven by sea surface temperature (SST) anomalies in the tropical Atlantic. Winters of northern Europe and eastern Canada turned cooler and drier whereas southern Europe and the eastern United States experienced warmer and wetter winters without Amazon runoff. Significant warming over the Arctic reduced the local sea-ice extent and enhanced the high latitude river runoff. More importantly, our simulations caution against extreme exploitation of rivers for its far-reaching consequences on climate.
Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations
Authors: Prins Bram P. , Kuchenbaecker Karoline B. , Bao Yanchun , Smart Melissa , Zabaneh Delilah , Fatemifar Ghazaleh , Luan Jian’an , Wareham Nick J. , Scott Robert A. , Perry John R. B. , Langenberg Claudia , Benzeval Michaela , Kumari Meena , Zeggini Eleftheria 
Published: September 2017

AbstractSerum biomarker levels are associated with the risk of complex diseases. Here, we aimed to gain insights into the genetic architecture of biomarker traits which can reflect health status. We performed genome-wide association analyses for twenty serum biomarkers involved in organ function and reproductive health. 9,961 individuals from the UK Household Longitudinal Study were genotyped using the Illumina HumanCoreExome array and variants imputed to the 1000 Genomes Project and UK10K haplotypes. We establish a polygenic heritability for all biomarkers, confirm associations of fifty-four established loci, and identify five novel, replicating associations at genome-wide significance. A low-frequency variant, rs28929474, (beta = 0.04, P = 2 × 10−10) was associated with levels of alanine transaminase, an indicator of liver damage. The variant is located in the gene encoding serine protease inhibitor, low levels of which are associated with alpha-1 antitrypsin deficiency which leads to liver disease. We identified novel associations (rs78900934, beta = 0.05, P = 6 × 10−12; rs2911280, beta = 0.09, P = 6 × 10−10) for dihydroepiandrosterone sulphate, a precursor to major sex-hormones, and for glycated haemoglobin (rs12819124, beta = −0.03, P = 4 × 10−9; rs761772, beta = 0.05, P = 5 × 10−9). rs12819124 is nominally associated with risk of type 2 diabetes. Our study offers insights into the genetic architecture of well-known and less well-studied biomarkers.
Delayed hypersensitivity to nanosecond pulsed electric field in electroporated cells
Authors: Jensen Sarah D. , Khorokhorina Vera A. , Muratori Claudia , Pakhomov Andrei G. , Pakhomova Olga N. 
Published: September 2017

AbstractWe demonstrate that conditioning of mammalian cells by electroporation with nanosecond pulsed electric field (nsPEF) facilitates their response to the next nsPEF treatment. The experiments were designed to unambiguously separate the electroporation-induced sensitization and desensitization effects. Electroporation was achieved by bursts of 300-ns, 9 kV/cm pulses (50 Hz, n = 3–100) and quantified by propidium dye uptake within 11 min after the nsPEF exposure. We observed either sensitization to nsPEF or no change (when the conditioning was either too weak or too intense, or when the wait time after conditioning was too short). Within studied limits, conditioning never caused desensitization. With settings optimal for sensitization, the second nsPEF treatment became 2.5 times (25 °C) or even 6 times (37 °C) more effective than the same nsPEF treatment delivered without conditioning. The minimum wait time required for sensitization development was 30 s, with still longer delays increasing the effect. We show that the delayed hypersensitivity was not mediated by either cell swelling or oxidative effect of the conditioning treatment; biological mechanisms underlying the delayed electrosensitization remain to be elucidated. Optimizing nsPEF delivery protocols to induce sensitization can reduce the dose and adverse side effects of diverse medical treatments which require multiple pulse applications.
Spatially encoded fast single-molecule fluorescence spectroscopy with full field-of-view
Authors: Tang Jialei , Sun Yangyang , Pang Shuo , Han Kyu Young 
Published: September 2017

AbstractWe report a simple single-molecule fluorescence imaging method that increases the temporal resolution of any type of array detector by >5-fold with full field-of-view. We spread single-molecule spots to adjacent pixels by rotating a mirror in the detection path during the exposure time of a single frame, which encodes temporal information into the spatial domain. Our approach allowed us to monitor fast blinking of an organic dye, the dissociation kinetics of very short DNA and conformational changes of biomolecules with much improved temporal resolution than the conventional method. Our technique is useful when a large field-of-view is required, for example, in the case of weakly interacting biomolecules or cellular imaging.
Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice
Authors: Sugui Janyce A. , Rose Stacey R. , Nardone Glenn , Swamydas Muthulekha , Lee Chyi-Chia R. , Kwon-Chung Kyung J. , Lionakis Michail S. 
Published: September 2017

AbstractDelayed diagnosis in invasive aspergillosis (IA) contributes to its high mortality. Gliotoxin (GT) and bis-methyl-gliotoxin (bmGT) are secondary metabolites produced by Aspergillus during invasive, hyphal growth and may prove diagnostically useful. Because IA pathophysiology and GT’s role in virulence vary depending on the underlying host immune status, we hypothesized that GT and bmGT production in vivo may differ in three mouse models of IA that mimic human disease. We defined temporal kinetics of GT and bmGT in serum, bronchoalveolar lavage fluid (BALF) and lungs of A. fumigatus-infected chronic granulomatous disease (CGD), hydrocortisone-treated, and neutropenic mice. We harvested lungs for assessment of fungal burden, histology and GT/bmGT biosynthetic genes’ mRNA induction. GT levels were higher in neutropenic versus CGD or steroid-treated lungs. bmGT was persistently detected only in CGD lungs. GT, but not bmGT, was detected in 71% of sera and 50% of BALF of neutropenic mice; neither was detected in serum/BALF of CGD or steroid-treated mice. Enrichment of GT in Aspergillus-infected neutropenic lung correlated with fungal burden and hyphal length but not induction of GT biosynthetic genes. In summary, GT is detectable in mouse lungs, serum and BALF during neutropenic IA, suggesting that GT may be useful to diagnose IA in neutropenic patients.
Optimal stress and deformation partition in gradient materials for better strength and tensile ductility: A numerical investigation
Authors: Wang Yao , Yang Guangxue , Wang Wenjing , Wang Xi , Li Qiang , Wei Yujie 
Published: September 2017

AbstractInspired by recent progress in developing gradient materials with excellent performances, here we report a systematic finite-element based investigation to show how the strength and tensile ductility of gradient crystalline metals depend on their microstructure characteristics. We reveal that the yielding strength of polycrystalline metals with gradient grain size can be significantly enhanced at no reduction in ductility. By employing a representative 3D voronoi gradient sample, we demonstrate that the redistribution of stress and deformation in the gradient structure - stronger grains carry more load and ductile ones share more deformation - accounts for the realized optimal property in strength and ductility. In addition, the hardenability of the ductile domain is beneficial to circumvent pre-mature plastic instability in gradient samples.
Functional Characterization of Two Elongases of Very Long-Chain Fatty Acid from Tenebrio molitor L. (Coleoptera: Tenebrionidae)
Authors: Zheng Tianxiang , Li Hongshuang , Han Na , Wang Shengyin , Hackney Price Jennifer , Wang Minzi , Zhang Dayu 
Published: September 2017

AbstractThe elongases of very long chain fatty acid (ELOVL or ELO) are essential in the biosynthesis of fatty acids longer than C14. Here, two ELO full-length cDNAs (TmELO1, TmELO2) from the yellow mealworm (Tenebrio molitor L.) were isolated and the functions were characterized. The open reading frame (ORF) lengths of TmELO1 and TmELO2 were 1005 bp and 972 bp, respectively and the corresponding peptide sequences each contained several conserved motifs including the histidine-box motif HXXHH. Phylogenetic analysis demonstrated high similarity with the ELO of Tribolium castaneum and Drosophila melanogaster. Both TmELO genes were expressed at various levels in eggs, 1st and 2nd instar larvae, mature larvae, pupae, male and female adults. Injection of dsTmELO1 but not dsTmELO2 RNA into mature larvae significantly increased mortality although RNAi did not produce any obvious changes in the fatty acid composition in the survivors. Heterologous expression of TmELO genes in yeast revealed that TmELO1 and TmELO2 function to synthesize long chain and very long chain fatty acids.
Hemoglobin level, a prognostic factor for nasal extranodal natural killer/T-cell lymphoma patients from stage I to IV: A validated prognostic nomogram
Authors: Cao Jianzhong , Lan Shengmin , Shen Liuhai , Si Hongwei , Xiao Huan , Yuan Qiang , Li Xue , Li Hongwei , Guo Ruyuan 
Published: September 2017

AbstractAlthough nasal extranodal natural killer/T-cell lymphoma (nasal ENKL) shares some prognostic factors with other lymphomas, seldom studies had explored the prognostic value of hemoglobin. The ENKL cases in stage I–IV during 2000 to 2015 were collected from two medical centers (group A, n = 192), and were randomly divided into the group B (n = 155) and C (n = 37). Although the significant factors identified by the univariate analysis differed between the group A and B, the multivariate Cox regression indicated the same factors. C-index of the model was slightly better than Yang’s, but its integrated Brier score (IBS) was obviously lower than Yang’s both in the group A and B. Additionally, minimal depth of random survival forest (RSF) classifier confirmed that the prognostic ability of hemoglobin was better than age both in the group A and B. In the calibration of the nomogram, the predicted 3-year or 5-year OS of our nomogram well agreed with the corresponding actual OS. In conclusion, Hemoglobin is a prognostic factor for nasal ENKL patients in stage I - IV, and integrating it into a validated prognostic nomogram, whose generalization error is the smallest among the evaluated models, can be used to predict the patients’ outcome.
Increased 15-PGDH expression leads to dysregulated resolution responses in stromal cells from patients with chronic tendinopathy
Authors: Dakin Stephanie G. , Ly Lucy , Colas Romain A. , Oppermann Udo , Wheway Kim , Watkins Bridget , Dalli Jesmond , Carr Andrew J. 
Published: September 2017

AbstractThe mechanisms underpinning the failure of inflammation to resolve in diseased musculoskeletal soft tissues are unknown. Herein, we studied bioactive lipid mediator (LM) profiles of tendon-derived stromal cells isolated from healthy donors and patients with chronic tendinopathy. Interleukin(IL)-1β treatment markedly induced prostaglandin biosynthesis in diseased compared to healthy tendon cells, and up regulated the formation of several pro-resolving mediators including 15-epi-LXA4 and MaR1. Incubation of IL-1β stimulated healthy tendon cells with 15-epi-LXA4 or MaR1 down-regulated PGE2 and PGD2 production. When these mediators were incubated with diseased cells, we only found a modest down regulation in prostanoid concentrations, whereas it led to significant decreases in IL-6 and Podoplanin expression. In diseased tendon cells, we also found increased 15-Prostaglandin Dehydrogenase (15-PGDH) expression as well as increased concentrations of both 15-epi-LXA4 and MaR1 further metabolites, 15-oxo-LXA4 and 14-oxo-MaR1. Inhibition of 15-PGDH using either indomethacin or SW033291 significantly reduced the further conversion of 15-epi-LXA4 and MaR1 and regulated expression of IL-6, PDPN and STAT-1. Taken together these results suggest that chronic inflammation in musculoskeletal soft tissues may result from dysregulated LM-SPM production, and that inhibition of 15-PGDH activity together with promoting resolution using SPM represents a novel therapeutic strategy to resolve chronic tendon inflammation.
Novel selective, potent naphthyl TRPM8 antagonists identified through a combined ligand- and structure-based virtual screening approach
Authors: Beccari Andrea R. , Gemei Marica , Lo Monte Matteo , Menegatti Nazareno , Fanton Marco , Pedretti Alessandro , Bovolenta Silvia , Nucci Cinzia , Molteni Angela , Rossignoli Andrea , Brandolini Laura , Taddei Alessandro , Za Lorena , Liberati Chiara , Vistoli Giulio 
Published: September 2017

AbstractTransient receptor potential melastatin 8 (TRPM8), a nonselective cation channel, is the predominant mammalian cold temperature thermosensor and it is activated by cold temperatures and cooling compounds, such as menthol and icilin. Because of its role in cold allodynia, cold hyperalgesia and painful syndromes TRPM8 antagonists are currently being pursued as potential therapeutic agents for the treatment of pain hypersensitivity. Recently TRPM8 has been found in subsets of bladder sensory nerve fibres, providing an opportunity to understand and treat chronic hypersensitivity. However, most of the known TRPM8 inhibitors lack selectivity, and only three selective compounds have reached clinical trials to date. Here, we applied two virtual screening strategies to find new, clinics suitable, TRPM8 inhibitors. This strategy enabled us to identify naphthyl derivatives as a novel class of potent and selective TRPM8 inhibitors. Further characterization of the pharmacologic properties of the most potent compound identified, compound 1, confirmed that it is a selective, competitive antagonist inhibitor of TRPM8. Compound 1 also proved itself active in a overreactive bladder model in vivo. Thus, the novel naphthyl derivative compound identified here could be optimized for clinical treatment of pain hypersensitivity in bladder disorders but also in different other pathologies.
The Arabidopsis MTP8 transporter determines the localization of manganese and iron in seeds
Authors: Chu Heng-Hsuan , Car Suzana , Socha Amanda L. , Hindt Maria N. , Punshon Tracy , Guerinot Mary Lou 
Published: September 2017

AbstractUnderstanding how seeds obtain and store nutrients is key to developing crops with higher agronomic and nutritional value. We have uncovered unique patterns of micronutrient localization in seeds using synchrotron X-ray fluorescence (SXRF). Although all four members of the Arabidopsis thaliana Mn-CDF family can transport Mn, here we show that only mtp8-2 has an altered Mn distribution pattern in seeds. In an mtp8-2 mutant, Mn no longer accumulates in hypocotyl cortex cells and sub-epidermal cells of the embryonic cotyledons, but rather accumulates with Fe in the cells surrounding the vasculature, a pattern previously shown to be determined by the vacuolar transporter VIT1. We also show that MTP8, unlike the other three Mn-CDF family members, can transport Fe and is responsible for localization of Fe to the same cells that store Mn. When both the VIT1 and MTP8 transporters are non-functional, there is no accumulation of Fe or Mn in specific cell types; rather these elements are distributed amongst all cell types in the seed. Disruption of the putative Fe binding sites in MTP8 resulted in loss of ability to transport Fe but did not affect the ability to transport Mn.
Uncovering the effect of low-frequency static magnetic field on tendon-derived cells: from mechanosensing to tenogenesis
Authors: Pesqueira Tamagno , Costa-Almeida Raquel , Gomes Manuela E. 
Published: September 2017

AbstractMagnetotherapy has been receiving increased attention as an attractive strategy for modulating cell physiology directly at the site of injury, thereby providing the medical community with a safe and non-invasive therapy. Yet, how magnetic field influences tendon cells both at the cellular and molecular levels remains unclear. Thus, the influence of a low-frequency static magnetic field (2 Hz, 350 mT) on human tendon-derived cells was studied using different exposure times (4 and 8 h; short-term studies) and different regimens of exposure to an 8h-period of magnetic stimulation (continuous, every 24 h or every 48 h; long-term studies). Herein, 8 h stimulation in short-term studies significantly upregulated the expression of tendon-associated genes SCX, COL1A1, TNC and DCN (p < 0.05) and altered intracellular Ca2+ levels (p < 0.05). Additionally, every 24 h regimen of stimulation significantly upregulated COL1A1, COL3A1 and TNC at day 14 in comparison to control (p < 0.05), whereas continuous exposure differentially regulated the release of the immunomodulatory cytokines IL-1β and IL-10 (p < 0.001) but only at day 7 in comparison to controls. Altogether, these results provide new insights on how low-frequency static magnetic field fine-tune the behaviour of tendon cells according to the magnetic settings used, which we foresee to represent an interesting candidate to guide tendon regeneration.
Deep Neural Network Probabilistic Decoder for Stabilizer Codes
Authors: Krastanov Stefan , Jiang Liang 
Published: September 2017

AbstractNeural networks can efficiently encode the probability distribution of errors in an error correcting code. Moreover, these distributions can be conditioned on the syndromes of the corresponding errors. This paves a path forward for a decoder that employs a neural network to calculate the conditional distribution, then sample from the distribution - the sample will be the predicted error for the given syndrome. We present an implementation of such an algorithm that can be applied to any stabilizer code. Testing it on the toric code, it has higher threshold than a number of known decoders thanks to naturally finding the most probable error and accounting for correlations between errors.
Identification of immunity-related genes in Plutella xylostella in response to fungal peptide destruxin A: RNA-Seq and DGE analysis
Authors: Shakeel Muhammad , Xu Xiaoxia , Xu Jin , Zhu Xun , Li Shuzhong , Zhou Xianqiang , Yu Jialin , Xu Xiaojing , Hu Qiongbo , Yu Xiaoqiang , Jin Fengliang 
Published: September 2017

AbstractPlutella xylostellahas become the major lepidopteran pest ofBrassicaowing to its strong ability of resistance development to a wide range of insecticides. Destruxin A, a mycotoxin of entomopathogenic fungus,Metarhizium anisopliae, has broad-spectrum insecticidal effects. However, the interaction mechanism of destruxin A with the immune system ofP. xylostellaat genomic level is still not well understood. Here, we identified 129 immunity-related genes, including pattern recognition receptors, signal modulators, few members of main immune pathways (Toll, Imd, and JAK/STAT), and immune effectors inP. xylostellain response to destruxin A at three different time courses (2 h, 4 h, and 6 h). It is worthy to mention that the immunity-related differentially expressed genes (DEGs) analysis exhibited 30, 78, and 72 up-regulated and 17, 13, and 6 down-regulated genes inP. xylostellaafter destruxin A injection at 2 h, 4 h, and 6 h, respectively, compared to control. Interestingly, our results revealed that the expression of antimicrobial peptides that play a vital role in insect immune system was up-regulated after the injection of destruxin A. Our findings provide a detailed information on immunity-related DEGs and reveal the potential ofP. xylostellato limit the infection of fungal peptide destruxin A by increasing the activity of antimicrobial peptides.
MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis
Authors: Liu Yamin , Wang Mei , luo Yunquan , Chen Jian , lu Yiyu , Shi Yulin , Tang Chenchen , Zhou Qianmei , Zhang Hui , Hu Yuanjia , Su Shibing , Chen Qilong 
Published: September 2017

AbstractHepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes.
Molecular characterization of cell-free eccDNAs in human plasma
Authors: Zhu Jing , Zhang Fan , Du Meijun , Zhang Peng , Fu Songbin , Wang Liang 
Published: September 2017

AbstractExtrachromosomal circular DNAs (eccDNAs) have been reported in most eukaryotes. However, little is known about the cell-free eccDNA profiles in circulating system such as blood. To characterize plasma cell-free eccDNAs, we performed sequencing analysis in 26 libraries from three blood donors and negative controls. We identified thousands of unique plasma eccDNAs in the three subjects. We observed proportional eccDNA increase with initial DNA input. The detected eccDNAs were also associated with circular DNA enrichment efficiency. Increasing the sequencing depth in an additional sample identified many more eccDNAs with highly heterogenous molecular structure. Size distribution of eccDNAs varied significantly from 31 bp to 19,989 bp. We found significantly higher GC content in smaller eccDNAs (<500 bp) than the larger ones (>500 bp) (p < 0.01). We also found an enrichment of eccDNAs at exons and 3′UTR (enrichment folds from 1.36 to 3.1) as well as the DNase hypersensitive sites (1.58–2.42 fold), H3K4Me1 (1.23–1.42 fold) and H3K27Ac (1.33–1.62 fold) marks. Junction sequence analysis suggested fundamental role of nonhomologous end joining mechanism during eccDNA formation. Further characterization of the extracellular eccDNAs in peripheral blood will facilitate understanding of their molecular mechanisms and potential clinical utilities.