bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association analysis of chronic lymphocytic leukaemia, Hodgkin lymphoma and multiple myeloma identifies pleiotropic risk loci
Authors: Law Philip J. , Sud Amit , Mitchell Jonathan S. , Henrion Marc , Orlando Giulia , Lenive Oleg , Broderick Peter , Speedy Helen E. , Johnson David C. , Kaiser Martin , Weinhold Niels , Cooke Rosie , Sunter Nicola J. , Jackson Graham H. , Summerfield Geoffrey , Harris Robert J. , Pettitt Andrew R. , Allsup David J. , Carmichael Jonathan , Bailey James R. , Pratt Guy , Rahman Thahira , Pepper Chris , Fegan Chris , von Strandmann Elke Pogge , Engert Andreas , Försti Asta , Chen Bowang , Filho Miguel Inacio da Silva , Thomsen Hauke , Hoffmann Per , Noethen Markus M. , Eisele Lewin , Jöckel Karl-Heinz , Allan James M. , Swerdlow Anthony J. , Goldschmidt Hartmut , Catovsky Daniel , Morgan Gareth J. , Hemminki Kari , Houlston Richard S. 
Published: January 2017

AbstractB-cell malignancies (BCM) originate from the same cell of origin, but at different maturation stages and have distinct clinical phenotypes. Although genetic risk variants for individual BCMs have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. We explored genome-wide association studies of chronic lymphocytic leukaemia (CLL, N = 1,842), Hodgkin lymphoma (HL, N = 1,465) and multiple myeloma (MM, N = 3,790). We identified a novel pleiotropic risk locus at 3q22.2 (NCK1, rs11715604, P = 1.60 × 10−9) with opposing effects between CLL (P = 1.97 × 10−8) and HL (P = 3.31 × 10−3). Eight established non-HLA risk loci showed pleiotropic associations. Within the HLA region, Ser37 + Phe37 in HLA-DRB1 (P = 1.84 × 10−12) was associated with increased CLL and HL risk (P = 4.68 × 10−12), and reduced MM risk (P = 1.12 × 10−2), and Gly70 in HLA-DQB1 (P = 3.15 × 10−10) showed opposing effects between CLL (P = 3.52 × 10−3) and HL (P = 3.41 × 10−9). By integrating eQTL, Hi-C and ChIP-seq data, we show that the pleiotropic risk loci are enriched for B-cell regulatory elements, as well as an over-representation of binding of key B-cell transcription factors. These data identify shared biological pathways influencing the development of CLL, HL and MM. The identification of these risk loci furthers our understanding of the aetiological basis of BCMs.
Reduction of radiation loss at small-radius bend using spoof surface plasmon polariton transmission line
Authors: Tang Wen Xuan , Zhang Hao Chi , Liu Jun Feng , Xu Jie , Cui Tie Jun 
Published: January 2017

AbstractSpoof surface plasmon polariton (SPP) has been realized at low frequencies through corrugated metallic structures. As two-dimensional application, the ultrathin SPP transmission lines (TLs) have been proposed with great potentials for microwave compact circuits due to the strong field confinement and enhancement, as well as controllable dispersive properties. In this paper, we examine the radiation loss at small-radius bend, which may cause severe crosstalk in highly-integrated circuits or systems, for the SPP TLs. We theoretically analyze that the SPP TL has essential merit of low radiation loss, and show better performance of SPP TL than the conventional microstrip line through numerical simulations and experiments. Both simulated and measured results demonstrate that the new type of transmission line can efficiently suppress the radiation loss at small-radius bend, and hence reduce the crosstalk in circuits and systems.
The natural retinoprotectant chrysophanol attenuated photoreceptor cell apoptosis in an N-methyl-N-nitrosourea-induced mouse model of retinal degenaration
Authors: Lin Fan-Li , Lin Cheng-Hui , Ho Jau-Der , Yen Jing-Lun , Chang Hung-Ming , Chiou George C. Y. , Cheng Yu-Wen , Hsiao George 
Published: January 2017

AbstractRetinitis pigmentosa (RP) is an inherited photoreceptor-degenerative disease, and neuronal degeneration in RP is exacerbated by glial activation. Cassia seed (Jue-ming-zi) is a traditional herbal medicine commonly used to treat ocular diseases in Asia. In this report, we investigated the retina-protective effect of chrysophanol, an active component of Cassia seed, in an N-methyl-N-nitrosourea (MNU)-induced mouse model of RP. We determined that chrysophanol inhibited the functional and morphological features of MNU-induced retinal degeneration using scotopic electroretinography (ERG), optical coherence tomography (OCT), and immunohistochemistry analysis of R/G opsin and rhodopsin. Furthermore, TUNEL assays revealed that chrysophanol attenuated MNU-induced photoreceptor cell apoptosis and inhibited the expression of the apoptosis-associated proteins PARP, Bax, and caspase-3. In addition, chrysophanol ameliorated reactive gliosis, as demonstrated by a decrease in GFAP immunolabeling, and suppressed the activation of matrix metalloproteinase (MMP)-9-mediated gelatinolysis. In vitro studies indicated that chrysophanol inhibited lipopolysaccharide (LPS)-induced iNOS and COX-2 expression in the BV2 mouse microglia cell line and inhibited MMP-9 activation in primary microglia. Our results demonstrate that chrysophanol provided neuroprotective effects and inhibited glial activation, suggesting that chrysophanol might have therapeutic value for the treatment of human RP and other retinopathies.
Neutrophils are dispensable in the modulation of T cell immunity against cutaneous HSV-1 infection
Authors: Hor Jyh Liang , Heath William R. , Mueller Scott N. 
Published: January 2017

AbstractNeutrophils rapidly infiltrate sites of inflammation during peripheral infection or tissue injury. In addition to their well described roles as pro-inflammatory phagocytes responsible for pathogen clearance, recent studies have demonstrated a broader functional repertoire including mediating crosstalk between innate and adaptive arms of the immune system. Specifically, neutrophils have been proposed to mediate antigen transport to lymph nodes (LN) to modulate T cell priming and to influence T cell migration to infected tissues. Using a mouse model of cutaneous herpes simplex virus type 1 (HSV-1) infection we explored potential contributions of neutrophils toward anti-viral immunity. While a transient, early influx of neutrophils was triggered by dermal scarification, we did not detect migration of neutrophils from the skin to LN. Furthermore, despite recruitment of neutrophils into LN from the blood, priming and expansion of CD4+ and CD8+ T cells was unaffected following neutrophil depletion. Finally, we found that neutrophils were dispensable for the migration of effector T cells into infected skin. Our study suggests that the immunomodulatory roles of neutrophils toward adaptive immunity may be context-dependent, and are likely determined by the type of pathogen and anatomical site of infection.
c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro
Authors: Yu Xiaoyu , Liu Wenwen , Fan Zhaomin , Qian Fuping , Zhang Daogong , Han Yuechen , Xu Lei , Sun Gaoying , Qi Jieyu , Zhang Shasha , Tang Mingliang , Li Jianfeng , Chai Renjie , Wang Haibo 
Published: January 2017

Abstractc-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.
Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation
Authors: Sheets Lavinia 
Published: January 2017

AbstractAccumulation of excess glutamate plays a central role in eliciting the pathological events that follow intensely loud noise exposures and ischemia-reperfusion injury. Glutamate excitotoxicity has been characterized in cochlear nerve terminals, but much less is known about whether excess glutamate signaling also contributes to pathological changes in sensory hair cells. I therefore examined whether glutamate excitotoxicity damages hair cells in zebrafish larvae exposed to drugs that mimic excitotoxic trauma. Exposure to ionotropic glutamate receptor (iGluR) agonists, kainic acid (KA) or N-methyl-D-aspartate (NMDA), contributed to significant, progressive hair cell loss in zebrafish lateral-line organs. To examine whether hair-cell loss was a secondary effect of excitotoxic damage to innervating neurons, I exposed neurog1a morphants—fish whose hair-cell organs are devoid of afferent and efferent innervation—to KA or NMDA. Significant, dose-dependent hair-cell loss occurred in neurog1a morphants exposed to either agonist, and the loss was comparable to wild-type siblings. A survey of iGluR gene expression revealed AMPA-, Kainate-, and NMDA-type subunits are expressed in zebrafish hair cells. Finally, hair cells exposed to KA or NMDA appear to undergo apoptotic cell death. Cumulatively, these data reveal that excess glutamate signaling through iGluRs induces hair-cell death independent of damage to postsynaptic terminals.
Progression-related loss of stromal Caveolin 1 levels fosters the growth of human PC3 xenografts and mediates radiation resistance
Authors: Panic Andrej , Ketteler Julia , Reis Henning , Sak Ali , Herskind Carsten , Maier Patrick , Rübben Herbert , Jendrossek Verena , Klein Diana 
Published: January 2017

AbstractDespite good treatment results in localized prostate tumors, advanced disease stages usually have a pronounced resistance to chemotherapy and radiotherapy. The membrane protein caveolin-1 (Cav1) functions here as an important oncogene. Therefore we examined the impact of stromal Cav1 expression for tumor growth and sensitivity to ionizing radiation (IR). Silencing of Cav1 expression in PC3 cells resulted in increased tumor growth and a reduced growth delay after IR when compared to tumors generated by Cav1-expressing PC3 cells. The increased radiation resistance was associated with increasing amounts of reactive tumor stroma and a Cav1 re-expression in the malignant epithelial cells. Mimicking the human situation these results were confirmed using co-implantation of Cav1-silenced PC3 cells with Cav1-silenced or Cav1-expressing fibroblasts. Immunohistochemically analysis of irradiated tumors as well as human prostate tissue specimen confirmed that alterations in stromal-epithelial Cav1 expressions were accompanied by a more reactive Cav1-reduced tumor stroma after radiation and within advanced prostate cancer tissues which potentially mediates the resistance to radiation treatment. Conclusively, the radiation response of human prostate tumors is critically regulated by Cav1 expression in stromal fibroblasts. Loss of stromal Cav1 expression in advanced tumor stages may thus contribute to resistance of these tumors to radiotherapy.
Click-Chemistry Based High Throughput Screening Platform for Modulators of Ras Palmitoylation
Authors: Ganesan Lakshmi , Shieh Peyton , Bertozzi Carolyn R. , Levental Ilya 
Published: January 2017

AbstractPalmitoylation is a widespread, reversible lipid modification that has been implicated in regulating a variety of cellular processes. Approximately one thousand proteins are annotated as being palmitoylated, and for some of these, including several oncogenes of the Ras and Src families, palmitoylation is indispensable for protein function. Despite this wealth of disease-relevant targets, there are currently few effective pharmacological tools to interfere with protein palmitoylation. One reason for this lack of development is the dearth of assays to efficiently screen for small molecular inhibitors of palmitoylation. To address this shortcoming, we have developed a robust, high-throughput compatible, click chemistry-based approach to identify small molecules that interfere with the palmitoylation of Ras, a high value therapeutic target that is mutated in up to a third of human cancers. This assay design shows excellent performance in 384-well format and is sensitive to known, non-specific palmitoylation inhibitors. Further, we demonstrate an ideal counter-screening strategy, which relies on a target peptide from an unrelated protein, the Src-family kinase Fyn. The screening approach described here provides an integrated platform to identify specific modulators of palmitoylated proteins, demonstrated here for Ras and Fyn, but potentially applicable to pharmaceutical targets involved in a variety of human diseases.
Biocapacity optimization in regional planning
Authors: Guo Jianjun , Yue Dongxia , Li Kai , Hui Cang 
Published: January 2017

AbstractEcological overshoot has been accelerating across the globe. Optimizing biocapacity has become a key to resolve the overshoot of ecological demand in regional sustainable development. However, most literature has focused on reducing ecological footprint but ignores the potential of spatial optimization of biocapacity through regional planning of land use. Here we develop a spatial probability model and present four scenarios for optimizing biocapacity of a river basin in Northwest China. The potential of enhanced biocapacity and its effects on ecological overshoot and water consumption in the region were explored. Two scenarios with no restrictions on croplands and water use reduced the overshoot by 29 to 53%, and another two scenarios which do not allow croplands and water use to increase worsened the overshoot by 11 to 15%. More spatially flexible transition rules of land use led to higher magnitude of change after optimization. However, biocapacity optimization required a large amount of additional water resources, casting considerable pressure on the already water-scarce socio-ecological system. Our results highlight the potential for policy makers to manage/optimize regional land use which addresses ecological overshoot. Investigation on the feasibility of such spatial optimization complies with the forward-looking policies for sustainable development and deserves further attention.
High-throughput sheathless and three-dimensional microparticle focusing using a microchannel with arc-shaped groove arrays
Authors: Zhao Qianbin , Zhang Jun , Yan Sheng , Yuan Dan , Du Haiping , Alici Gursel , Li Weihua 
Published: January 2017

AbstractSheathless particle focusing which utilises the secondary flow with a high throughput has great potential for use in microfluidic applications. In this work, an innovative particle focusing method was proposed. This method makes use of a mechanism that takes advantage of secondary flow and inertial migration. The device was a straight channel with arrays of arc-shaped grooves on the top surface. First, the mechanism and expected focusing phenomenon are explained using numerical simulation of the flow field and force balance. A simulation of particle trajectories was conducted as a reference, and then a series of experiments was designed and the effects of changes in particle size, flow rate and quantity of the groove structure were discussed. The microscopic images show that this particle focusing method performed well for different size particles, and the results agreed well with the theory and simulated results. Finally, the channel successfully concentrated Jurkat cells, which showed a good compatibility in the biological assay field. In this work, the arc-shaped groove channel was demonstrated to have the ability to achieve high-throughput, sheathless and three-dimensional particle focusing with simple operations.
Transit peptide elements mediate selective protein targeting to two different types of chloroplasts in the single-cell C4 species Bienertia sinuspersici
Authors: Wimmer Diana , Bohnhorst Philipp , Shekhar Vinay , Hwang Inhwan , Offermann Sascha 
Published: January 2017

AbstractBienertia sinuspersici is a terrestrial plant that performs C4 photosynthesis within individual cells through operating a carbon concentrating mechanism between different subcellular domains including two types of chloroplasts. It is currently unknown how differentiation of two highly specialized chloroplasts within the same cell occurs as no similar cases have been reported. Here we show that this differentiation in photosynthetic cells of B. sinuspersici is enabled by a transit peptide (TP) mediated selective protein targeting mechanism. Mutations in the TPs cause loss of selectivity but not general loss of chloroplast import, indicating the mechanism operates by specifically blocking protein accumulation in one chloroplast type. Hybrid studies indicate that this selectivity is transferable to transit peptides of plants which perform C4 by cooperative function of chloroplasts between two photosynthetic cells. Codon swap experiments as well as introducing an artificial bait mRNA show that RNA affects are not crucial for the sorting process. In summary, our analysis shows how the mechanism of subcellular targeting to form two types of chloroplast within the same cell can be achieved. This information is not only crucial for understanding single-cell C4 photosynthesis; it provides new insights in control of subcellular protein targeting in cell biology.
Mechanistic interplay between ceramide and insulin resistance
Authors: Reali Federico , Morine Melissa J. , Kahramanoğulları Ozan , Raichur Suryaprakash , Schneider Hans-Christoph , Crowther Daniel , Priami Corrado 
Published: January 2017

AbstractRecent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase. Our analysis suggests the pivotal role of ceramide synthase, serine palmitoyltransferase and dihydroceramide desaturase involved in the de novo synthesis and the salvage pathways in influencing insulin resistance versus its regulation.
Ethylene response pathway modulates attractiveness of plant roots to soybean cyst nematode Heterodera glycines
Authors: Hu Yanfeng , You Jia , Li Chunjie , Williamson Valerie M. , Wang Congli 
Published: January 2017

AbstractPlant parasitic nematodes respond to root exudates to locate their host roots. In our studies second stage juveniles of Heterodera glycines, the soybean cyst nematode (SCN), quickly migrated to soybean roots in Pluronic F-127 gel. Roots of soybean and non-host Arabidopsis treated with the ethylene (ET)-synthesis inhibitor aminoethoxyvinylglycine (AVG) were more attractive to SCN than untreated roots, and significantly more nematodes penetrated into roots. Moreover, Arabidopsis ET insensitive mutants (ein2, ein2-1, ein2-5, ein3-1, ein5-1, and ein6) were more attractive than wild-type plants. Conversely, the constitutive triple-response mutant ctr1-1, was less attractive to SCN. While ET receptor gain-of-function mutant ein4-1 attracted more SCN than the wild-type, there were no significant differences in attractiveness between another gain-of-function ET receptor mutant, etr1-3, or the loss-of-function mutants etr1-7 and ers1-3 and the wild type. Expression of the reporter construct EBS: β-glucuronidase (GUS) was detected in Arabidopsis root tips as early as 6 h post infection, indicating that ET signaling was activated in Arabidopsis early by SCN infection. These results suggest that an active ET signaling pathway reduces root attractiveness to SCN in a way similar to that reported for root-knot nematodes, but opposite to that suggested for the sugar beet cyst nematode Heterodera schachtii.
Endothelia-Targeting Protection by Escin in Decompression Sickness Rats
Authors: Zhang Kun , Jiang Zhongxin , Ning Xiaowei , Yu Xuhua , Xu Jiajun , Buzzacott Peter , Xu Weigang 
Published: January 2017

AbstractEndothelial dysfunction is involved in the pathogenesis of decompression sickness (DCS) and contributes substantively to subsequent inflammatory responses. Escin, the main active compound in horse chestnut seed extract, is well known for its endothelial protection and anti-inflammatory properties. This study aimed to investigate the potential protection of escin against DCS in rats. Escin was administered orally to adult male rats for 7 d (1.8 mg/kg/day) before a simulated air dive. After decompression, signs of DCS were monitored, and blood and pulmonary tissue were sampled for the detection of endothelia related indices. The incidence and mortality of DCS were postponed and decreased significantly in rats treated with escin compared with those treated with saline (P < 0.05). Escin significantly ameliorated endothelial dysfunction (increased serum E-selectin and ICAM-1 and lung Wet/Dry ratio, decreased serum NO), and oxidative and inflammatory responses (increased serum MDA, MPO, IL-6 and TNF-α) (P < 0.05 or P < 0.01). The results suggest escin has beneficial effects on DCS related to its endothelia-protective properties and might be a drug candidate for DCS prevention and treatment.
Cell Death Mechanisms in Tumoral and Non-Tumoral Human Cell Lines Triggered by Photodynamic Treatments: Apoptosis, Necrosis and Parthanatos
Authors: Soriano J. , Mora-Espí I. , Alea-Reyes M. E. , Pérez-García L. , Barrios L. , Ibáñez E. , Nogués C. 
Published: January 2017

AbstractCell death triggered by photodynamic therapy can occur through different mechanisms: apoptosis, necrosis or autophagy. However, recent studies have demonstrated the existence of other mechanisms with characteristics of both necrosis and apoptosis. These new cell death pathways, collectively termed regulated necrosis, include a variety of processes triggered by different stimuli. In this study, we evaluated the cell death mechanism induced by photodynamic treatments with two photosensitizers, meso-tetrakis (4-carboxyphenyl) porphyrin sodium salt (Na-H2TCPP) and its zinc derivative Na-ZnTCPP, in two human breast epithelial cell lines, a non-tumoral (MCF-10A) and a tumoral one (SKBR-3). Viability assays showed that photodynamic treatments with both photosensitizers induced a reduction in cell viability in a concentration-dependent manner and no dark toxicity was observed. The cell death mechanisms triggered were evaluated by several assays and cell line-dependent results were found. Most SKBR-3 cells died by either necrosis or apoptosis. By contrast, in MCF-10A cells, necrotic cells and another cell population with characteristics of both necrosis and apoptosis were predominant. In this latter population, cell death was PARP-dependent and translocation of AIF to the nucleus was observed in some cells. These characteristics are related with parthanatos, being the first evidence of this type of regulated necrosis in the field of photodynamic therapy.