bluuebunny/crossref_metadata_2025_split huggingface dataset:
A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation
Authors: Castell Alina , Yan Qinzi , Fawkner Karin , Hydbring Per , Zhang Fan , Verschut Vasiliki , Franco Marcela , Zakaria Siti Mariam , Bazzar Wesam , Goodwin Jacob , Zinzalla Giovanna , Larsson Lars-Gunnar 
Published: June 2018

AbstractMYC is a key player in tumor development, but unfortunately no specific MYC-targeting drugs are clinically available. MYC is strictly dependent on heterodimerization with MAX for transcription activation. Aiming at targeting this interaction, we identified MYCMI-6 in a cell-based protein interaction screen for small inhibitory molecules. MYCMI-6 exhibits strong selective inhibition of MYC:MAX interaction in cells and in vitro at single-digit micromolar concentrations, as validated by split Gaussia luciferase, in situ proximity ligation, microscale thermophoresis and surface plasmon resonance (SPR) assays. Further, MYCMI-6 blocks MYC-driven transcription and binds selectively to the MYC bHLHZip domain with a KD of 1.6 ± 0.5 μM as demonstrated by SPR. MYCMI-6 inhibits tumor cell growth in a MYC-dependent manner with IC50 concentrations as low as 0.5 μM, while sparing normal cells. The response to MYCMI-6 correlates with MYC expression based on data from 60 human tumor cell lines and is abrogated by MYC depletion. Further, it inhibits MYC:MAX interaction, reduces proliferation and induces massive apoptosis in tumor tissue from a MYC-driven xenograft tumor model without severe side effects. Since MYCMI-6 does not affect MYC expression, it is a unique molecular tool to specifically target MYC:MAX pharmacologically and it has good potential for drug development.
Group size effects on inter-blink interval as an indicator of antipredator vigilance in wild baboons
Authors: Matsumoto-Oda Akiko , Okamoto Kohei , Takahashi Kenta , Ohira Hideki 
Published: June 2018

AbstractVigilance in animals is an important means for predator detection. Animals living in groups reduce their predation risk as more individuals are present. In contrast to most other animals studied, many studies on primates do not support the prediction that individual vigilance will decline as group size increases. For animals to obtain visual information during vigilance behaviour, their eyes must be open. Therefore, if animals are able to perceive differential risk of predation, the inter-blink interval (eye-opening) should increase, and the blink duration (eye-closure) should decrease under higher predation risk. We tested this prediction by measuring inter-blink interval in wild anubis baboons (Papio anubis) in peripheral and centre individuals within a group, and between larger and smaller groups. We found that the inter-blink interval for young males, often located at the front edge of the group, was longer than that of adult males, adult females, and young females, often located in the center of the group, and that the inter-blink interval for adult males was longer when the group was smaller. These results suggest that inter-blink interval can be used as an indicator of primate vigilance toward predators.
Validation of Assaying Carcinoembryonic Antigen in Human Serum by Using Immunomagnetic Reduction
Authors: Wei Po-Li , Lee Long-Teng , Tseng Li-Ming , Huang Kai-Wen 
Published: June 2018

AbstractImmunomagnetic reduction (IMR) is a method to assay biomolecules by utilizing antibody functionalized magnetic nanoparticles. For clinical validation, important analytic performances of assaying carcinoembryonic antigen (CEA) using IMR are characterized. Furthermore, IMR is applied to assay carcinoembryonic antigen (CEA) in human serum for clinical validation. A total of 118 healthy controls and 79 patients with colorectal cancer (CRC) are recruited in this study. For comparison, assays using chemiluminometric immunoassay (CLIA) are also done for quantizing CEA in these serum samples. The results reveal a high correlation in terms of serum CEA concentration detected via IMR and CLIA is found (r = 0.963). However, IMR shows higher clinical sensitivity and specificity than those of CLIA. Moreover, the rate of false positives for smoking subjects is clearly reduced through the use of IMR. All the results demonstrate IMR is a promising alternative assay for serum CEA to diagnose CRC.
Actin polymerization is activated by terahertz irradiation
Authors: Yamazaki Shota , Harata Masahiko , Idehara Toshitaka , Konagaya Keiji , Yokoyama Ginji , Hoshina Hiromichi , Ogawa Yuichi 
Published: June 2018

AbstractPolymerization of monomeric actin into filaments has pivotal roles in cell motility, growth, differentiation, and gene expression. Therefore, techniques of manipulating actin polymerization, including actin-binding chemicals, have been developed for understanding and regulating multiple biological functions. Here, we demonstrate that irradiation with terahertz (THz) waves is a novel method of modulating actin polymerization. When actin polymerization reaction is performed under irradiation with 0.46 THz waves generated by a Gyrotron, actin polymerization was observed to be activated by monitoring the fluorescence of pyrene actin fluorophores. We also observed the number of actin filaments under a fluorescence microscope using the polymerized actin probe SiR-actin. The number of actin filaments was increased by 3.5-fold after THz irradiation for 20 min. When the THz irradiation was applied to a steady-state actin solution, in which elongation and depolymerization of actin filaments were equilibrated, increased actin polymerization was observed, suggesting that the THz irradiation activates actin polymerization, at least in the elongation process. These results suggest that THz waves could be applied for manipulating biomolecules and cells.
Changes in intestinal gene expression and microbiota composition during late pregnancy are mouse strain dependent
Authors: Elderman Marlies , Hugenholtz Floor , Belzer Clara , Boekschoten Mark , de Haan Bart , de Vos Paul , Faas Marijke 
Published: June 2018

AbstractHormones and placental factors are thought to underlie the maternal immunological changes during pregnancy. However, as several intestinal microbiota are linked to immune modulations, we hypothesized that the intestinal microbiota are altered during pregnancy in favor of species associated with pregnancy associated immune modulations. We studied the fecal microbiota composition (MITchip) and intestinal and peripheral immune cells (microarray and flow cytometry) in pregnant and non-pregnant C57BL/6 and BALB/c mice. Pregnancy influenced intestinal microbiota diversity and composition, however in a mouse strain dependent way. Pregnant BALB/c mice had, among others, a relative higher abundance of Lactobacillus paracasei et rel., Roseburia intestinalis et rel. and Eubacterium hallii et rel., as compared to non-pregnant BALB/c mice, while the microbiota composition in B6 mice hardly changed during pregnancy. Additionally, intestinal immunological pathways were changed during pregnancy, however again in a mouse strain dependent way. Correlations between various bacteria and immunological genes were observed. Our data do support a role for the microbiome in changing immune responses in pregnancy. However, other factors are also involved, such as for instance changes in SCFA or changes in sensitivity to bacteria, since although immunological changes are observed in B6 mice, hardly any changes in microbiota were found in this strain. Follow up studies are needed to study the exact relationship between these parameters.
Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry
Authors: Kakeda Shingo , Watanabe Keita , Katsuki Asuka , Sugimoto Koichiro , Igata Natsuki , Ueda Issei , Igata Ryohei , Abe Osamu , Yoshimura Reiji , Korogi Yukunori 
Published: June 2018

AbstractThere is a growing body of evidence to support the involvement of proinflammatory cytokines in the pathophysiology of depression; however, no previous studies have examined the relationship between cytokines and the brain morphology of patients with major depressive disorder (MDD). We therefore evaluated the relationship between serum cytokine levels and cortical thinning during the first depressive episode in drug-naïve patients with MDD. We measured the serum cytokine levels (IL-1β, IL-6, IFN-γ, and TNFα), and whole-brain cortical thickness and hippocampal subfield volumes on brain magnetic resonance imaging (MRI) using surface-based morphometry in 40 patients with MDD and 47 healthy volunteers (controls). Only the serum IL-6 level was significantly higher in patients with MDD than in controls. The prefrontal cortex (PFC) thickness was significantly reduced in patients with MDD, and showed a significant inverse correlation with the serum IL-6 level. Although high serum IL-6 levels were correlated with reduced left subiculum and right CA1, CA3, CA4, GC-DG, subiculum, and whole hippocampus volumes, the presence or absence of MDD had no effect on the volume of any hippocampal subfields. Our results suggest that IL-6 may play a key role in the morphological changes in the PFC during the early stage of MDD.
Phospholipase D1 regulation of TNF-alpha protects against responses to LPS
Authors: Urbahn Marc-Andre , Kaup Sonja Charlotte , Reusswig Friedrich , Krüger Irena , Spelleken Martina , Jurk Kerstin , Klier Meike , Lang Philipp A. , Elvers Margitta 
Published: June 2018

AbstractSepsis is a systemic inflammatory disorder with organ dysfunction and represents the leading cause of mortality in non-coronary intensive care units. A key player in septic shock is Tumor Necrosis Factor-alpha (TNF-α). Phospholipase (PL)D1 is involved in the regulation of TNF-α upon ischemia/reperfusion injury in mice. In this study we analyzed the impact of PLD1 in the regulation of TNF-α, inflammation and organ damage in experimental sepsis. PLD1 deficiency increased survival of mice and decreased vital organ damage after LPS injections. Decreased TNF-α plasma levels and reduced migration of leukocytes and platelets into lungs was associated with reduced apoptosis in lung and liver tissue of PLD1 deficient mice. PLD1 deficient platelets contribute to preserved outcome after LPS-induced sepsis because platelets exhibit an integrin activation defect suggesting reduced platelet activation in PLD1 deficient mice. Furthermore, reduced thrombin generation of PLD1 deficient platelets might be responsible for reduced fibrin formation in lungs suggesting reduced disseminated intravascular coagulation (DIC). The analysis of Pld1fl/fl-PF4-Cre mice revealed that migration of neutrophils and cell apoptosis in septic animals is not due to platelet-mediated processes. The present study has identified PLD1 as a regulator of innate immunity that may be a new target to modulate sepsis.
Intradermal injection of low dose human regulatory T cells inhibits skin inflammation in a humanized mouse model
Authors: Landman Sija , de Oliveira Vivian L. , van Erp Piet E. J. , Fasse Esther , Bauland Stijn C. G. , Joosten Irma , Koenen Hans J. P. M. 
Published: June 2018

AbstractRecent regulatory T cell (Treg) based clinical trials support their therapeutic potential in transplantation and auto-inflammatory diseases. However, large numbers of Treg are needed to accomplish therapeutic efficacy. Local injection at the site of inflammation (targeted delivery) may lower the numbers needed for therapy. We evaluated if local delivery of low numbers of human Treg by intradermal injection was able to prevent skin inflammation, using the humanized mouse huPBL-SCID-huSkin allograft model. A dose of only 1 × 105 freshly isolated, non expanded Treg injected intradermally in close proximity to the transplanted human skin prevented inflammation of the grafted tissue induced by 4 × 107 IP injected human allogeneic PBMCs, (ratio Treg:PBMC = 1:400), as indicated by the inhibition of epidermal thickening, sustained Keratin-10 expression, the absence of Keratin-16 up regulation and prevention of human CD3+ T cell influx. A concomitant reduction of human T cells was observed in lymph nodes and spleen of the mice. Injection of Treg at the contralateral side was also shown to inhibit skin inflammation, suggesting that the inflammatory response was regulated both locally and systemically. In conclusion, local application of Treg may be an attractive way to suppress inflammation in vivo without the need for prior ex vivo expansion.
Monitoring ratio of carbon to nitrogen (C/N) in wheat and barley leaves by using spectral slope features with branch-and-bound algorithm
Authors: Xu Xingang , Yang Guijun , Yang Xiaodong , Li Zhenhai , Feng Haikuan , Xu Bo , Zhao Xiaoqing 
Published: June 2018

AbstractRatio of carbon to nitrogen concentration (C/N) that can illuminate metabolic status of C and N in crop leaves is one valuable indicator for crop nutrient diagnosis. This study explored the feasibility of using spectral slope features from hyperspectral measurements with Branch-and-Bound (BB) algorithm to monitor leaf C/N in wheat and barley. Experimental data from barley in 2010 and wheat in 2012 were collected and used. The analyses prove that leaf C/N is closely related to leaf N concentration (LNC), which implies that it is feasible to apply spectral technology to monitor leaf C/N in that LNC may have been effectivly estimated by hyperspectral measurements. The results also show that many spectral slope features proposed in this study exhibit the significant correlations with leaf C/N. The best slope feature could evaluate changes of leaf C/N well, with R2 of 0.63 for wheat, 0.68 for barley and 0.65 for both species combined, respectively. using BB algorithm with input of optiaml four slope features can improve the accuracy of leaf C/N estimations with R2 over 0.81. It is concluded that using the spectral slope new features with BB method appears very promising and potential for remotely monitoring leaf C/N in crops.
Discovery of peptide probes to modulate oxytocin-type receptors of insects
Authors: Keov Peter , Liutkevičiūtė Zita , Hellinger Roland , Clark Richard J. , Gruber Christian W. 
Published: June 2018

AbstractThe oxytocin/vasopressin signalling system is conserved across the animal kingdom. In insects, the role of oxytocin-type (inotocin) neuropeptides has only been studied in locusts, beetles and ants, but their physiology continues to be poorly understood. One reason for this knowledge deficit is the lack of available research tools to complement functional genomics efforts. Consequently, ligands to probe insect inotocin receptors are essential. In this study, we sought to identify novel agonists and antagonists of the inotocin receptor from the representative model species Tribolium castaneum and Lasius niger. Drawing upon known ligands of the human receptors, we examined the pharmacology of the plant-derived cyclotide kalata B7 and the synthetic oxytocin analogue atosiban. Kalata B7 is a weak partial agonist of both inotocin receptors. This is the first reported direct interaction of cyclotides with an insect receptor, an observation that may explain their presumed role in herbivore defence. Furthermore, we discovered atosiban is an antagonist of the Tribolium receptor, which may provide a useful probe to investigate the functionality of inotocin signalling in beetles and related insect species. Our findings will enable further examination of insect inotocin receptor pharmacology and physiology, and may trigger studies to comprehend the interaction of plant cyclotides and insects.
The influence of meteorological factors on tuberculosis incidence in Southwest China from 2006 to 2015
Authors: Xiao Yuanyuan , He Limei , Chen Ying , Wang Qinying , Meng Qiong , Chang Wei , Xiong Lifen , Yu Zhen 
Published: June 2018

AbstractThe influence of meteorological determinants on tuberculosis (TB) incidence remains severely under-discussed, especially through the perspective of time series analysis. In the current study, we used a distributed lag nonlinear model (DLNM) to analyze a 10-year series of consecutive surveillance data. We found that, after effectively controlling for autocorrelation, the changes in meteorological factors related to temperature, humidity, wind and sunshine were significantly associated with subsequent fluctuations in TB incidence: average temperature was inversely associated with TB incidence at a lag period of 2 months; total precipitation and minimum relative humidity were also inversely associated with TB incidence at lag periods of 3 and 4 months, respectively; average wind velocity and total sunshine hours exhibited an instant rather than lagged influence on TB incidence. Our study results suggest that preceding meteorological factors may have a noticeable effect on future TB incidence; informed prevention and preparedness measures for TB can therefore be constructed on the basis of meteorological variations.
A low-cost and high-performance thin-film composite forward osmosis membrane based on an SPSU/PVC substrate
Authors: Zheng Ke , Zhou Shaoqi , Zhou Xuan 
Published: June 2018

AbstractA low-cost sulfonated polysulfone (SPSU)/poly(vinyl chloride) (PVC) substrate based high-performance thin-film composite (TFC) forward osmosis (FO) membrane was fabricated in this work. The results showed that the morphologies of the substrates were looser and more porous, and the porosity, pure water permeability, surface hydrophilicity, and average pore size of the substrates significantly improved after the SPSU was introduced into the PVC substrates. Furthermore, the SPSU/PVC-based TFC membranes exhibited rougher, looser and less crosslinked polyamide active layers than the neat PVC-based TFC membrane. The water permeability obviously increased, and the structure parameter dramatically declined. Moreover, the FO performance significantly improved (e.g. the water flux of TFC2.5 reached 25.53/48.37 LMH under FO/PRO mode by using 1.0 M NaCl/DI water as the draw/feed solution, while the specific salt flux exhibited a low value of 0.10/0.09 g/L). According to the results, it can be concluded that 2.5% of SPSU was the optimal blend ratio, which exhibited the lowest sulfonated material blend ratio compared to the data reported in the literature. Hence, this is a feasible and low-cost fabrication approach for high-performance FO membrane by using the cheap PVC and low blend-ratio SPSU as the membrane materials.
Cold atmospheric plasma causes a calcium influx in melanoma cells triggering CAP-induced senescence
Authors: Schneider Christin , Gebhardt Lisa , Arndt Stephanie , Karrer Sigrid , Zimmermann Julia L. , Fischer Michael J. M. , Bosserhoff Anja-Katrin 
Published: June 2018

AbstractCold atmospheric plasma (CAP) is a promising approach in anti-cancer therapy, eliminating cancer cells with high selectivity. However, the molecular mechanisms of CAP action are poorly understood. In this study, we investigated CAP effects on calcium homeostasis in melanoma cells. We observed increased cytoplasmic calcium after CAP treatment, which also occurred in the absence of extracellular calcium, indicating the majority of the calcium increase originates from intracellular stores. Application of previously CAP-exposed extracellular solutions also induced cytoplasmic calcium elevations. A substantial fraction of this effect remained when the application was delayed for one hour, indicating the chemical stability of the activating agent(s). Addition of ryanodine and cyclosporin A indicate the involvement of the endoplasmatic reticulum and the mitochondria. Inhibition of the cytoplasmic calcium elevation by the intracellular chelator BAPTA blocked CAP-induced senescence. This finding helps to understand the molecular influence and the mode of action of CAP on tumor cells.
Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics
Authors: Nagy-Szakal Dorottya , Barupal Dinesh K. , Lee Bohyun , Che Xiaoyu , Williams Brent L. , Kahn Ellie J. R. , Ukaigwe Joy E. , Bateman Lucinda , Klimas Nancy G. , Komaroff Anthony L. , Levine Susan , Montoya Jose G. , Peterson Daniel L. , Levin Bruce , Hornig Mady , Fiehn Oliver , Lipkin W. Ian 
Published: June 2018

AbstractThe pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.
X-ray study of the double radio relic Abell 3376 with Suzaku
Authors: Urdampilleta I. , Akamatsu H. , Mernier F. , Kaastra J. S. , de Plaa J. , Ohashi T. , Ishisaki Y. , Kawahara H. 
Published: June 2018

We present an X-ray spectral analysis of the nearby double radio relic merging cluster Abell 3376 (z = 0.046), observed with the Suzaku XIS instrument. These deep (∼360 ks) observations cover the entire double relic region in the outskirts of the cluster. These diffuse radio structures are amongst the largest and arc-shaped relics observed in combination with large-scale X-ray shocks in a merging cluster. We confirm the presence of a stronger shock (ℳW = 2.8 ± 0.4) in the western direction at r ∼ 26′, derived from a temperature and surface brightness discontinuity across the radio relic. In the east, we detect a weaker shock (ℳE = 1.5 ± 0.1) at r ∼ 8′, possibly associated with the “notch” of the eastern relic, and a cold front at r ∼ 3′. Based on the shock speed calculated from the Mach numbers, we estimate that the dynamical age of the shock front is ∼0.6 Gyr after core passage, indicating that Abell 3376 is still an evolving merging cluster and that the merger is taking place close to the plane of the sky. These results are consistent with simulations and optical and weak lensing studies from the literature.