bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment
Authors: Mathot P , Grandin M , Devailly G , Souaze F , Cahais V , Moran S , Campone M , Herceg Z , Esteller M , Juin P , Mehlen P , Dante R 
Published: October 2017

AbstractBreast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications. Here, we investigated the mechanisms underlying the changes in gene expression patterns associated with the cross-talk between breast cancer cells and the stroma. From RNAseq data obtained from breast cancer cell lines grown in presence of CAF-secreted factors, we identified 372 upregulated genes, exhibiting an expression level positively correlated with the stromal content of breast cancer specimens. Furthermore, we observed that gene expression changes were not mediated through significant DNA methylation changes. Nevertheless, CAF-secreted factors but also stromal content of the tumors remarkably activated specific genes characterized by a DNA methylation pattern: hypermethylation at transcription start site and shore regions. Experimental approaches (inhibition of DNA methylation, knockdown of methyl-CpG-binding domain protein 2 and chromatin immunoprecipitation assays) indicated that this set of genes was epigenetically controlled. These data elucidate the importance of epigenetics marks in the cancer cell reprogramming induced by stromal cell and indicated that the interpreters of the DNA methylation signal have a major role in the response of the cancer cells to the microenvironment.
Real-time observation of polymerase-promoter contact remodeling during transcription initiation
Authors: Meng Cong A. , Fazal Furqan M. , Block Steven M. 
Published: October 2017

AbstractCritical contacts made between the RNA polymerase (RNAP) holoenzyme and promoter DNA modulate not only the strength of promoter binding, but also the frequency and timing of promoter escape during transcription. Here, we describe a single-molecule optical-trapping assay to study transcription initiation in real time, and use it to map contacts formed between σ70 RNAP holoenzyme from E. coli and the T7A1 promoter, as well as to observe the remodeling of those contacts during the transition to the elongation phase. The strong binding contacts identified in certain well-known promoter regions, such as the −35 and −10 elements, do not necessarily coincide with the most highly conserved portions of these sequences. Strong contacts formed within the spacer region (−10 to −35) and with the −10 element are essential for initiation and promoter escape, respectively, and the holoenzyme releases contacts with promoter elements in a non-sequential fashion during escape.
Hydrogen substituted graphdiyne as carbon-rich flexible electrode for lithium and sodium ion batteries
Authors: He Jianjiang , Wang Ning , Cui Zili , Du Huiping , Fu Lin , Huang Changshui , Yang Ze , Shen Xiangyan , Yi Yuanping , Tu Zeyi , Li Yuliang 
Published: October 2017

AbstractOrganic electrodes are potential alternatives to current inorganic electrode materials for lithium ion and sodium ion batteries powering portable and wearable electronics, in terms of their mechanical flexibility, function tunability and low cost. However, the low capacity, poor rate performance and rapid capacity degradation impede their practical application. Here, we concentrate on the molecular design for improved conductivity and capacity, and favorable bulk ion transport. Through an in situ cross-coupling reaction of triethynylbenzene on copper foil, the carbon-rich frame hydrogen substituted graphdiyne film is fabricated. The organic film can act as free-standing flexible electrode for both lithium ion and sodium ion batteries, and large reversible capacities of 1050 mAh g−1 for lithium ion batteries and 650 mAh g−1 for sodium ion batteries are achieved. The electrode also shows a superior rate and cycle performances owing to the extended π-conjugated system, and the hierarchical pore bulk with large surface area.
Aromatic C-H addition of ketones to imines enabled by manganese catalysis
Authors: Zhou Bingwei , Hu Yuanyuan , Liu Ting , Wang Congyang 
Published: October 2017

AbstractSelectivity control of varied C–H bonds in a complex molecule is a long-standing goal and still a great challenge in C–H activation field. Most often, such selectivity is achieved by the innate reactivity of different C–H bonds. In this context, the classic Mannich reaction of acetophenone derivatives and imines is ascribed to the more reactive C(sp3)–H bonds α to the carbonyl, with the much less reactive aromatic C(sp2)–H bonds remaining intact. Herein we report an aromatic C(sp2)–H addition of ketones to imines enabled by manganese catalysis, which totally reverses the innate reactivity of C–H bonds α to the carbonyl and those on the aromatic ring. Diverse products of ortho-C–H aminoalkylated ketones, cyclized exo-olefinic isoindolines, and three-component methylated isoindolines can be successfully accessed under mild reaction conditions, which significantly expands the synthetic utilities of ketones as simple bulk chemicals.
Inequality in genetic cancer risk suggests bad genes rather than bad luck
Authors: Stensrud Mats Julius , Valberg Morten 
Published: October 2017

AbstractHeritability is often estimated by decomposing the variance of a trait into genetic and other factors. Interpreting such variance decompositions, however, is not straightforward. In particular, there is an ongoing debate on the importance of genetic factors in cancer development, even though heritability estimates exist. Here we show that heritability estimates contain information on the distribution of absolute risk due to genetic differences. The approach relies on the assumptions underlying the conventional heritability of liability model. We also suggest a model unrelated to heritability estimates. By applying these strategies, we describe the distribution of absolute genetic risk for 15 common cancers. We highlight the considerable inequality in genetic risk of cancer using different metrics, e.g., the Gini Index and quantile ratios which are frequently used in economics. For all these cancers, the estimated inequality in genetic risk is larger than the inequality in income in the USA.
Bioluminescence imaging of G protein-coupled receptor activation in living mice
Authors: Kono Mari , Conlon Elizabeth G. , Lux Samantha Y. , Yanagida Keisuke , Hla Timothy , Proia Richard L. 
Published: October 2017

AbstractG protein-coupled receptors (GPCRs), a superfamily of cell-surface receptors involved in virtually all physiological processes, are the major target class for approved drugs. Imaging GPCR activation in real time in living animals would provide a powerful way to study their role in biology and disease. Here, we describe a mouse model that enables the bioluminescent detection of GPCR activation in real time by utilizing the clinically important GPCR, sphingosine-1-phosphate receptor 1 (S1P1). A synthetic S1P1 signaling pathway, designed to report the interaction between S1P1 and β-arrestin2 via the firefly split luciferase fragment complementation system, is genetically encoded in these mice. Upon receptor activation and subsequent β-arrestin2 recruitment, an active luciferase enzyme complex is produced, which can be detected by in vivo bioluminescence imaging. This imaging strategy reveals the dynamics and spatial specificity of S1P1 activation in normal and pathophysiologic contexts in vivo and can be applied to other GPCRs.
Taxonomic and functional turnover are decoupled in European peat bogs
Authors: Robroek Bjorn J. M. , Jassey Vincent E. J. , Payne Richard J. , Martí Magalí , Bragazza Luca , Bleeker Albert , Buttler Alexandre , Caporn Simon J. M. , Dise Nancy B. , Kattge Jens , Zając Katarzyna , Svensson Bo H. , van Ruijven Jasper , Verhoeven Jos T. A. 
Published: October 2017

AbstractIn peatland ecosystems, plant communities mediate a globally significant carbon store. The effects of global environmental change on plant assemblages are expected to be a factor in determining how ecosystem functions such as carbon uptake will respond. Using vegetation data from 56 Sphagnum-dominated peat bogs across Europe, we show that in these ecosystems plant species aggregate into two major clusters that are each defined by shared response to environmental conditions. Across environmental gradients, we find significant taxonomic turnover in both clusters. However, functional identity and functional redundancy of the community as a whole remain unchanged. This strongly suggests that in peat bogs, species turnover across environmental gradients is restricted to functionally similar species. Our results demonstrate that plant taxonomic and functional turnover are decoupled, which may allow these peat bogs to maintain ecosystem functioning when subject to future environmental change.
Multi-modal mechanophores based on cinnamate dimers
Authors: Zhang Huan , Li Xun , Lin Yangju , Gao Fei , Tang Zhen , Su Peifeng , Zhang Wenke , Xu Yuanze , Weng Wengui , Boulatov Roman 
Published: October 2017

AbstractMechanochemistry offers exciting opportunities for molecular-level engineering of stress-responsive properties of polymers. Reactive sites, sometimes called mechanophores, have been reported to increase the material toughness, to make the material mechanochromic or optically healable. Here we show that macrocyclic cinnamate dimers combine these productive stress-responsive modes. The highly thermally stable dimers dissociate on the sub-second timescale when subject to a stretching force of 1–2 nN (depending on isomer). Stretching a polymer of the dimers above this force more than doubles its contour length and increases the strain energy that the chain absorbs before fragmenting by at least 600 kcal per mole of monomer. The dissociation produces a chromophore and dimers are reformed upon irradiation, thus allowing optical healing of mechanically degraded parts of the material. The mechanochemical kinetics, single-chain extensibility, toughness and potentially optical properties of the dissociation products are tunable by synthetic modifications.
Montessori education: a review of the evidence base
Authors: Marshall Chloë 
Published: October 2017

AbstractThe Montessori educational method has existed for over 100 years, but evaluations of its effectiveness are scarce. This review paper has three aims, namely to (1) identify some key elements of the method, (2) review existing evaluations of Montessori education, and (3) review studies that do not explicitly evaluate Montessori education but which evaluate the key elements identified in (1). The goal of the paper is therefore to provide a review of the evidence base for Montessori education, with the dual aspirations of stimulating future research and helping teachers to better understand whether and why Montessori education might be effective.
Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells
Authors: Park Hae-Young , Tan Peck S. , Kavishna Ranmali , Ker Anna , Lu Jinhua , Chan Conrad E. Z. , Hanson Brendon J. , MacAry Paul A. , Caminschi Irina , Shortman Ken , Alonso Sylvie , Lahoud Mireille H. 
Published: October 2017

AbstractTargeting model antigens (Ags) to Clec9A on DC has been shown to induce, not only cytotoxic T cells, but also high levels of Ab. In fact, Ab responses against immunogenic Ag were effectively generated even in the absence of DC-activating adjuvants. Here we tested if targeting weakly immunogenic putative subunit vaccine Ags to Clec9A could enhance Ab responses to a level likely to be protective. The proposed “universal” influenza Ag, M2e and the enterovirus 71 Ag, SP70 were linked to anti-Clec9A Abs and injected into mice. Targeting these Ags to Clec9A greatly increased Ab titres. For optimal responses, a DC-activating adjuvant was required. For optimal responses, a boost injection was also needed, but the high Ab titres against the targeting construct blocked Clec9A-targeted boosting. Heterologous prime-boost strategies avoiding cross-reactivity between the priming and boosting targeting constructs overcame this limitation. In addition, targeting small amounts of Ag to Clec9A served as an efficient priming for a conventional boost with higher levels of untargeted Ag. Using this Clec9A-targeted priming, conventional boosting strategy, M2e immunisation protected mice from infection with lethal doses of influenza H1N1 virus.
Dual Biomembrane Force Probe enables single-cell mechanical analysis of signal crosstalk between multiple molecular species
Authors: Ju Lining , Chen Yunfeng , Li Kaitao , Yuan Zhou , Liu Baoyu , Jackson Shaun P. , Zhu Cheng 
Published: October 2017

AbstractConventional approaches for studying receptor-mediated cell signaling, such as the western blot and flow cytometry, are limited in three aspects: 1) The perturbing preparation procedures often alter the molecules from their native state on the cell; 2) Long processing time before the final readout makes it difficult to capture transient signaling events (<1 min); 3) The experimental environments are force-free, therefore unable to visualize mechanical signals in real time. In contrast to these methods in biochemistry and cell biology that are usually population-averaged and non-real-time, here we introduce a novel single-cell based nanotool termed dual biomembrane force probe (dBFP). The dBFP provides precise controls and quantitative readouts in both mechanical and chemical terms, which is particularly suited for juxtacrine signaling and mechanosensing studies. Specifically, the dBFP allows us to analyze dual receptor crosstalk by quantifying the spatiotemporal requirements and functional consequences of the up- and down-stream signaling events. In this work, the utility and power of the dBFP has been demonstrated in four important dual receptor systems that play key roles in immunological synapse formation, shear-dependent thrombus formation, and agonist-driven blood clotting.
Postprandial Blood Glucose Outweighs Fasting Blood Glucose and HbA1c in screening Coronary Heart Disease
Authors: Jiang Jingjing , Zhao Lin , Lin Liu , Gui Minghui , Aleteng Qiqige , Wu Bingjie , Wang Shanshan , Pan Baishen , Ling Yan , Gao Xin 
Published: October 2017

AbstractThe objective of the present study is to assess the performance of fasting blood glucose (FBG), postprandial blood glucose (PBG), and glycated hemoglobin (HbA1c) as screening for coronary heart disease (CHD) in an inpatient population undergoing coronary angiography. 1852 consecutive patients scheduled for coronary angiography were classified into Normal Glucose Tolerance (NGT), Impaired Glucose Regulation (IGR), and diabetes, based on FBG, PBG, and HbA1c. Correlations of Gensini score with glucose metabolism and insulin resistance were analyzed. The associations between glycemic variables and Gensini score or the presence of CHD were analyzed by multiple linear regression and logistic regression, respectively. CHD was diagnosed in 488, 622, and 414 patients with NGT, IGR, and diabetes, respectively. Gensini score was positively correlated with FBG (r = 0.09, p < 0.01), PBG (r = 0.20, p < 0.01), and HbA1c (r = 0.19, p < 0.01). Gensini score was not correlated with fasting insulin (r = −0.081, p = 0.36), post-prandial insulin (r = −0.02, p = 0.61), or HOMAIR (r = −0.0059, p = 0.13). When FBG, PBG and HbA1c were pooled altogether, only PBG persisted in its association with Gensini score and the prevalence of CHD. The severity of CHD was associated with glucose rather than insulin resistance in this Chinese population. PBG was optimally correlated with the presence and severity of CHD.
Imaging Monitoring of Kupffer Cell Function and Hepatic Oxygen Saturation in Preneoplastic Changes During Cholangiocarcinogenesis
Authors: Lee Seunghyun , Kim Jung Hoon , Lee Jeong Hwa , Zen Yoh , Han Joon Koo 
Published: October 2017

AbstractWe investigated serial changes of the Kupffer cell (KC) function and hepatic oxygen saturation (sO2) using contrast-enhanced ultrasound imaging (CEUS) and photoacoustic imaging (PAI) in preneoplastic changes during cholangiocarcinogenesis induced by obstructive cholangitis and N-nitrosodimethylamine in a mouse model. The CEUS and PAI were performed to assess Sonazoid contrast agent uptake by KC and changes in the sO2 of liver parenchyma. An extensive bile ductular reaction, cystic dilatation, and epithelial hyperplasia with dysplastic changes were noted in the experimental group. During the preneoplastic changes, the parenchymal echogenicity on the Kupffer-phase of CEUS was continuously decreased in the experimental group, and which means that the Sonazoid phagocytosis by KC was decreased. The number of KCs was increased in the CD68 analysis, indicating functionally impaired KCs. There was a simultaneous serial decrease in sO2 on PAI measurement of the experimental group during the preneoplastic changes. The experimental group also showed significantly higher expression of hypoxia-inducible factor-1α and vascular endothelial growth factor protein. Our study demonstrated that KC dysfunction and hypoxic environmental changes were the factors influencing preneoplastic change during cholangiocarcinogenesis, and we could non-invasively monitor these changes using CEUS and PAI.
Myostatin inhibition prevents skeletal muscle pathophysiology in Huntington’s disease mice
Authors: Bondulich Marie K. , Jolinon Nelly , Osborne Georgina F. , Smith Edward J. , Rattray Ivan , Neueder Andreas , Sathasivam Kirupa , Ahmed Mhoriam , Ali Nadira , Benjamin Agnesska C. , Chang Xiaoli , Dick James R. T. , Ellis Matthew , Franklin Sophie A. , Goodwin Daniel , Inuabasi Linda , Lazell Hayley , Lehar Adam , Richard-Londt Angela , Rosinski Jim , Smith Donna L. , Wood Tobias , Tabrizi Sarah J. , Brandner Sebastian , Greensmith Linda , Howland David , Munoz-Sanjuan Ignacio , Lee Se-Jin , Bates Gillian P. 
Published: October 2017

AbstractHuntington’s disease (HD) is an inherited neurodegenerative disorder of which skeletal muscle atrophy is a common feature, and multiple lines of evidence support a muscle-based pathophysiology in HD mouse models. Inhibition of myostatin signaling increases muscle mass, and therapeutic approaches based on this are in clinical development. We have used a soluble ActRIIB decoy receptor (ACVR2B/Fc) to test the effects of myostatin/activin A inhibition in the R6/2 mouse model of HD. Weekly administration from 5 to 11 weeks of age prevented body weight loss, skeletal muscle atrophy, muscle weakness, contractile abnormalities, the loss of functional motor units in EDL muscles and delayed end-stage disease. Inhibition of myostatin/activin A signaling activated transcriptional profiles to increase muscle mass in wild type and R6/2 mice but did little to modulate the extensive Huntington’s disease-associated transcriptional dysregulation, consistent with treatment having little impact on HTT aggregation levels. Modalities that inhibit myostatin signaling are currently in clinical trials for a variety of indications, the outcomes of which will present the opportunity to assess the potential benefits of targeting this pathway in HD patients.
Circulating Haptoglobin and Metabolic Syndrome in Renal Transplant Recipients
Authors: Minović Isidor , Eisenga Michele F. , Riphagen Ineke J. , van den Berg Else , Kootstra-Ros Jenny , Frenay Anne-Roos S. , van Goor Harry , Rimbach Gerald , Esatbeyoglu Tuba , Levy Andy P. , Gaillard Carlo A. J. M. , Geleijnse Johanna M. , Eggersdorfer Manfred L. , Navis Gerjan J. , Kema Ido P. , Bakker Stephan J. L. 
Published: October 2017

AbstractHaptoglobin (Hp) is an acute phase protein that has recently been linked to components of the metabolic syndrome (MetS). We aimed to evaluate Hp as marker of MetS, and to assess its association with long-term outcome in renal transplant recipients (RTR). We measured plasma Hp in a prospective cohort of 699 stable RTR and 149 healthy controls. Median plasma Hp concentration in RTR was 1.4 [interquartile range (IQR), 1.0–1.8] g/L, which was higher compared to 1.1 [0.9–1.4] g/L in controls (P < 0.001). Hp was independently associated with the MetS (β = 0.10) (P = 0.005). During follow-up of 5.4 [4.8–6.1] years, 150 (21%) recipients died, of whom 60 (9%) due to cardiovascular causes, and 83 (12%) RTR developed graft failure. High (≥2.0 g/L) and low (≤0.9 g/L) plasma Hp were associated with increased risk of mortality (HR’s 2.3 [1.3–4.1] and 1.9 [1.0–3.5], resp.), predominantly cardiovascular. The association of high Hp lost significance upon adjustment for inflammation markers (HR 1.5 [0.8–2.7]), while low Hp was independently associated with mortality (HR 2.2 [1.2–4.0]). Hp was not associated with graft failure (P = 0.49). In conclusion, plasma Hp is independently associated with MetS in RTR. Importantly, high and low Hp are associated with increased mortality risk, independent of MetS.
Norrin protects optic nerve axons from degeneration in a mouse model of glaucoma
Authors: Leopold Stephanie A. , Zeilbeck Ludwig F. , Weber Gregor , Seitz Roswitha , Bösl Michael R. , Jägle Herbert , Fuchshofer Rudolf , Tamm Ernst R. , Ohlmann Andreas 
Published: October 2017

AbstractNorrin is a secreted signaling molecule activating the Wnt/β-catenin pathway. Since Norrin protects retinal neurons from experimental acute injury, we were interested to learn if Norrin attenuates chronic damage of retinal ganglion cells (RGC) and their axons in a mouse model of glaucoma. Transgenic mice overexpressing Norrin in the retina (Pax6-Norrin) were generated and crossed with DBA/2J mice with hereditary glaucoma and optic nerve axonal degeneration. One-year old DBA/2J/Pax6-Norrin animals had significantly more surviving optic nerve axons than their DBA/2J littermates. The protective effect correlated with an increase in insulin-like growth factor (IGF)-1 mRNA and an enhanced Akt phosphorylation in DBA/2J/Pax6-Norrin mice. Both mouse strains developed an increase in intraocular pressure during the second half of the first year and marked degenerative changes in chamber angle, ciliary body and iris structure. The degenerations were slightly attenuated in the chamber angle of DBA/2J/Pax6-Norrin mice, which showed a β-catenin increase in the trabecular meshwork. We conclude that high levels of Norrin and the subsequent constitutive activation of Wnt/β-catenin signaling in RGC protect from glaucomatous axonal damage via IGF-1 causing increased activity of PI3K-Akt signaling. Our results identify components of a protective signaling network preventing degeneration of optic nerve axons in glaucoma.
Fluorescence-based cell-specific detection for laser-capture microdissection in human brain
Authors: Rocco Brad R. , Oh Hyunjung , Shukla Rammohan , Mechawar Naguib , Sibille Etienne 
Published: October 2017

AbstractCell-specific molecular investigations of the human brain are essential for understanding the neurobiology of diseases, but are hindered by postmortem conditions and technical challenges. To address these issues we developed a multi-label fluorescence in situ hybridization protocol and a novel optical filter device to identify cell types and control for tissue autofluorescence. We show that these methods can be used with laser-capture microdissection for human brain tissue cell-specific molecular analysis.