bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive Notch2 signaling induces hepatic tumors in mice
Authors: Dill Michael T. , Tornillo Luigi , Fritzius Thorsten , Terracciano Luigi , Semela David , Bettler Bernhard , Heim Markus H. , Tchorz Jan S. 
Published: November 2012

Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCC) are the most common liver tumors and a leading cause for cancer-related death in men. Notch2 regulates cellular differentiation in the developing and adult liver. Although aberrant Notch signaling is implicated in various cancers, it is still unclear whether Notch2 regulates proliferation and differentiation in liver carcinogenesis and thereby contributes to HCC and CCC formation. Here, we investigated the oncogenic potential of constitutive Notch2 signaling in the liver. We show that liver-specific expression of the intracellular domain of Notch2 (N2ICD) in mice is sufficient to induce HCC formation and biliary hyperplasia. Specifically, constitutive N2ICD signaling in the liver leads to up-regulation of pro-proliferative genes and proliferation of hepatocytes and biliary epithelial cells (BECs). Using the diethylnitrosamine (DEN) HCC carcinogenesis model, we further show that constitutive Notch2 signaling accelerates DEN-induced HCC formation. DEN-induced HCCs with constitutive Notch2 signaling (DENN2ICD HCCs) exhibit a marked increase in size, proliferation, and expression of pro-proliferative genes when compared with HCCs from DEN-induced control mice (DENctrl HCCs). Moreover, DENN2ICD HCCs exhibit increased Sox9 messenger RNA (mRNA) levels and reduced Albumin and Alpha-fetoprotein mRNA levels, indicating that they are less differentiated than DENctrl HCCs. Additionally, DENN2ICD mice develop large hepatic cysts, dysplasia of the biliary epithelium, and eventually CCC. CCC formation in patients and DENN2ICD mice is accompanied by re-expression of hepatocyte nuclear factor 4α(HNF4α), possibly indicating dedifferentiation of BECs.

Conclusion

: Our data establish an oncogenic role for constitutive Notch2 signaling in liver cancer development.
High susceptibility to liver injury in IL-27 p28 conditional knockout mice involves intrinsic interferon-γ dysregulation of CD4+ T cells
Authors: Zhang Song , Liang Ruifang , Luo Wei , Liu Chang , Wu Xiaoli , Gao Yanan , Hao Jianlei , Cao Guangchao , Chen Xi , Wei Jun , Xia Siyuan , Li Zheng , Wen Ti , Wu Yunyun , Zhou Xinglong , Wang Puyue , Zhao Liqing , Wu Zhengzhou , Xiong Sidong , Gao Xiaoming , Gao Xiang , Chen Yongyan , Ge Qing , Tian Zhigang , Yin Zhinan 
Published: November 2012

Abstract

Interleukin (IL)-27, a newly discovered IL-12 family cytokine, is composed of p28 and EBI3. In this study,

CD11c-p28

f/f conditional knockout mice were generated to delete p28 specifically in dendritic cells (DCs). We demonstrated that in the absence of DC-derived p28, these mice were highly susceptible to both low and higher concentrations of concanavalin A (ConA) (5 mg/kg or 10 mg/kg), with extremely early and steady high levels of interferon-γ (IFN-γ) in sera. Neutralizing IFN-γ prevented ConA-induced liver damage in these mice, indicating a critical role of IFN-γ in this pathological process. Interestingly, the main source of the increased IFN-γ in

CD11c-p28

f/f mice was CD4+ T cells, but not natural killer T (NKT) cells. Depletion of CD4+, but not NK1.1+, cells completely abolished liver damage, whereas transferring CD4+ T cells from

CD11c-p28

f/f mice, but not from wild-type mice or

CD11c-p28

f/f
-
IFN

-γ−/− double knockout mice to CD4−/− mice, restored the increased liver damage. Further studies defined higher levels of IFN-γ and T-bet messenger RNA in naïve CD4+ T cells from

CD11c-p28

f/f mice, and these CD4+ T cells were highly responsive to both low and higher concentrations of anti-CD3, indicating a programmed functional alternation of CD4+ T cells.

Conclusion

: We provide a unique model for studying the pathology of CD4+ T cell–mediated liver injury and reveal a novel function of DC-derived p28 on ConA-induced fulminant hepatitis through regulation of the intrinsic ability for IFN-γ production by CD4+ T cells.
Contemporary fine‐grained bed sediment sources across the River Wensum Demonstration Test Catchment, UK
Authors: Collins A. L. , Zhang Y. S. , Hickinbotham R. , Bailey G. , Darlington S. , Grenfell S. E. , Evans R. , Blackwell M. 
Published: November 2012

AbstractBecause the sources of fine‐grained sediment problems in river systems are diffuse, it is essential to assemble catchment scale information for informing management strategies. Sediment source‐tracing procedures have increasingly been adopted in this respect. Accordingly, a recently refined composite tracing procedure was used to investigate contemporary sources of fine‐grained channel bed sediment in 11 sub‐catchments (364 km2) of the River Wensum Demonstration Test Catchment, in the eastern UK. The procedure incorporated a combination of statistical tests for discriminating source end members, plus numerical mass balance modelling incorporating weightings for within‐source tracer variations and tracer‐specific discriminatory power, as well as a combination of local and genetic algorithm optimisation coupled with Monte Carlo uncertainty analysis. Replicate Monte Carlo runs demonstrated the convergence of the modelling outputs within ±1% of the average medians. Relative frequency‐weighted average median source type contributions were estimated to range between 27%–69% (agricultural topsoils; predicted deviate median inputs 0%–98% and 9%–100%), 0%–38% (damaged road verges; predicted deviate median inputs 0%–58% and 0%–100%) and 21%–48% (channel banks/subsurface sources; predicted deviate median inputs 0%–50% and 4%–50%). The study provides further evidence of the importance of channel banks and damaged road verges as sediment sources and the need to include such areas in catchment sediment management strategies. Copyright © 2012 John Wiley & Sons, Ltd.
Age at menarche and risk of ovarian cancer: A meta‐analysis of epidemiological studies
Authors: Gong Ting‐Ting , Wu Qi‐Jun , Vogtmann Emily , Lin Bei , Wang Yong‐Lai 
Published: November 2012

AbstractEpidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta‐analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T‐T.G. and Q‐J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random‐effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case–control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75–0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case–control studies were 0.89 (95% CI = 0.76–1.03) and 0.84 (95% CI = 0.70–0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta‐analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.
Variation in PAH‐related DNA adduct levels among non‐smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype
Authors: Etemadi Arash , Islami Farhad , Phillips David H. , Godschalk Roger , Golozar Asieh , Kamangar Farin , Malekshah Akbar Fazel‐Tabar , Pourshams Akram , Elahi Seerat , Ghojaghi Farhad , Strickland Paul T. , Taylor Philip R. , Boffetta Paolo , Abnet Christian C. , Dawsey Sanford M. , Malekzadeh Reza , van Schooten Frederik J. 
Published: November 2012

AbstractPolycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never‐smokers. We tried to find a model to explain the relationship between variation in PAH‐related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly selected female never‐smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by32P‐postlabeling. Multivariable regression models were compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 108 nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non‐risk‐allele genotype, and was higher in the MPO homozygote risk‐allele genotype. The sum of risk alleles in these genes significantly correlated with the log‐adduct level (r = 0.4, p < 0.001). Compared with the environmental model, adding Phase I SNPs and NER capacity provided the best fit, and could explain 17% more of the variation in adduct levels. NER capacity was affected by polymorphisms in the MTHFR and ERCC1 genes. Female non‐smokers in this population had PAH‐related DNA adduct levels three to four times higher than smokers and occupationally‐exposed groups in previous studies, with large inter‐individual variation which could best be explained by a combination of Phase I genes and NER capacity.
microRNA and inflammatory gene expression as prognostic marker for overall survival in esophageal squamous cell carcinoma
Authors: Zhao Yiqiang , Schetter Aaron J. , Yang Geoffrey B. , Nguyen Giang , Mathé Ewy A. , Li Peng , Cai Hong , Yu Lei , Liu Fangfang , Hang Dong , Yang Haijun , Wang Xin Wei , Ke Yang , Harris Curtis C. 
Published: November 2012

AbstractMicroRNAs (miRNAs) and inflammatory genes have a role in the initiation and development of esophageal squamous cell carcinoma (ESCC). In our study, we examined the potential of using miRNA and inflammatory gene expression patterns as prognostic classifiers for ESCC. Five miRNAs and 25 inflammatory‐related genes were measured by quantitative reverse transcriptase PCR in tumor tissues and adjacent noncancerous tissues from 178 Chinese patients with ESCC. The expression levels of miR‐21 (p = 0.027), miR‐181b (p = 0.002) and miR‐146b (p = 0.021) in tumor tissue and miR‐21 (p = 0.003) in noncancerous tissue were associated with overall survival of patients. These data were combined to generate a miRNA risk score that was significantly associated with worse prognosis (p = 0.0001), suggesting that these miRNAs may be useful prognostic classifiers for ESCC. To construct an inflammatory gene prognostic classifier, we divided the population into training (n = 124) and test cohorts (n = 54). The expression levels of CRY61, CTGF and IL‐18 in tumor tissue and VEGF in adjacent noncancerous tissue were modestly associated with prognosis in the training cohort |Z‐score| > 1.5 and were subsequently used to construct a Cox regression‐based inflammatory risk score (IRS). IRS was significantly associated with survival in both the training cohort (p = 0.002) and the test cohort (p = 0.005). Furthermore, Cox regression models combining both miRNA risk score and IRS performed significantly better than models with either alone (p < 0.001 likelihood ratio test). Therefore, miRNA and inflammatory gene expression patterns, alone or in combination, have potential as prognostic classifiers for ESCC and may help to guide therapeutic decisions.
Recent advances in laser tweezers Raman spectroscopy (LTRS) for label‐free analysis of single cells
Authors: Chan James W. 
Published: November 2012

AbstractLaser tweezers Raman spectroscopy (LTRS), a technique that integrates optical tweezers with confocal Raman spectroscopy, is a variation of micro‐Raman spectroscopy that enables the manipulation and biochemical analysis of single biological particles in suspension. This article provides an overview of the LTRS method, with an emphasis on highlighting recent advances over the past several years in the development of the technology and several new biological and biomedical applications that have been demonstrated. A perspective on the future developments of this powerful cytometric technology will also be presented. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Raman spectroscopy coupled with advanced statistics for differentiating menstrual and peripheral blood
Authors: Sikirzhytskaya Aliaksandra , Sikirzhytski Vitali , Lednev Igor K. 
Published: November 2012

AbstractBody fluids are a common and important type of forensic evidence. In particular, the identification of menstrual blood stains is often a key step during the investigation of rape cases. Here, we report on the application of near‐infrared Raman microspectroscopy for differentiating menstrual blood from peripheral blood. We observed that the menstrual and peripheral blood samples have similar but distinct Raman spectra. Advanced statistical analysis of the multiple Raman spectra that were automatically (Raman mapping) acquired from the 40 dried blood stains (20 donors for each group) allowed us to build classification model with maximum (100%) sensitivity and specificity. We also demonstrated that despite certain common constituents, menstrual blood can be readily distinguished from vaginal fluid. All of the classification models were verified using cross‐validation methods. The proposed method overcomes the problems associated with currently used biochemical methods, which are destructive, time consuming and expensive. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An efficient method for computing the QTAIM topology of a scalar field: The electron density case
Authors: Rodríguez Juan I. 
Published: November 2012

AbstractAn efficient method for computing the quantum theory of atoms in molecules (QTAIM) topology of the electron density (or other scalar field) is presented. A modified Newton–Raphson algorithm was implemented for finding the critical points (CP) of the electron density. Bond paths were constructed with the second‐order Runge–Kutta method. Vectorization of the present algorithm makes it to scale linearly with the system size. The parallel efficiency decreases with the number of processors (from 70% to 50%) with an average of 54%. The accuracy and performance of the method are demonstrated by computing the QTAIM topology of the electron density of a series of representative molecules. Our results show that our algorithm might allow to apply QTAIM analysis to large systems (carbon nanotubes, polymers, fullerenes) considered unreachable until now. © 2012 Wiley Periodicals, Inc.
Complexes of 4‐substituted phenolates with HF and HCN: Energy decomposition and electronic structure analyses of hydrogen bonding
Authors: Szatyłowicz Halina , Krygowski Tadeusz M. , Fonseca Guerra Célia , Bickelhaupt F. Matthias 
Published: November 2012

AbstractWe have computationally studiedpara‐X‐substituted phenols and phenolates (X = NO, NO2, CHO, COMe, COOH, CONH2, Cl, F, H, Me, OMe, and OH) and their hydrogen‐bonded complexes with B−and HB (B = F and CN), respectively, at B3LYP/6‐311++G** and BLYP‐D/QZ4P levels of theory. Our purpose is to explore the structures and stabilities of these complexes. Moreover, to understand the emerging trends, we have analyzed the bonding mechanisms using the natural bond orbital scheme as well as Kohn–Sham molecular orbital (MO) theory in combination with quantitative energy decomposition analyses [energy decomposition analysis (EDA), extended transition state‐natural orbitals for chemical valence (ETS‐NOCV)]. These quantitative analyses allow for the construction of a simple physical model that explains all computational observations. © 2012 Wiley Periodicals, Inc.
Formal Semantics of Sign Languages
Authors: Zucchi Sandro 
Published: November 2012

AbstractThe paper discusses some issues that arise from research on sign languages in the area of formal semantics. Sign languages provide a unique standpoint to investigate semantic phenomena like donkey anaphora, indexical reference shift, and tense. Moreover, they pose a challenge for semantic theories, since movement verbs display gradient properties (semi‐continuous variations with semantic import). The paper presents and discusses some accounts that have been proposed.
Political Discourse Analysis: Exploring the Language of Politics and the Politics of Language
Authors: Dunmire Patricia L. 
Published: November 2012

AbstractThis essay overviews the body of research known as political discourse analysis (PDA). I begin by situating this work within the linguistic and political turns that took place in the latter part of the 20th century within the human and social sciences. I then discuss different conceptions of what comprisesthe politicaland the appropriate objects of study for PDA. Adopting an inclusive conception of politics and discourse, I consider the relationship between PDA and critical discourse analysis (CDA). I close with a review of studies of political discourse in terms of their theoretical and analytic frameworks and the socio‐political issues they address.
Structure and Substance in Artificial‐Phonology Learning, Part II: Substance
Authors: Moreton Elliott , Pater Joe 
Published: November 2012

AbstractArtificial analogues of natural‐language phonological patterns can often be learned in the lab from small amounts of training or exposure. The difficulty of a featurally‐defined pattern has been hypothesized to be affected by two main factors, its formal structure (the abstract logical relationships between the defining features) and its phonetic substance (the concrete phonetic interpretation of the pattern). This paper, the second of a two‐part series, reviews the experimental literature on phonetic substance, which is hypothesized to facilitate the acquisition of phonological patterns that resemble naturally‐occurring phonetic patterns. The effects of phonetic substance on pattern learning turn out to be elusive and unreliable in comparison with the robust effects of formal complexity (reviewed in Part I). If natural‐language acquisition is guided by the same inductive biases as are found in the lab, these results support a theory in which inductive bias shapes only the form, and channel bias shapes the content, of the sound patterns of the worlds languages.
Telechelic Polymers by Visible‐Light‐Induced Radical Coupling
Authors: Iskin Birol , Yilmaz Gorkem , Yagci Yusuf 
Published: November 2012

AbstractA simple and efficient method to prepare telechelics by visible‐light‐induced radical coupling is presented. Irradiation of the toluene solutions of bromo‐terminated polystyrenes prepared by atom transfer radical polymerization (ATRP) in the presence of an ester functional ATRP initiator and dimanganese decacarbonyl (Mn2(CO)10) at λ = 400–500 nm leads to the formation telechelic polymers through radical–radical coupling. Adaptability of the process for the preparation of mono‐ and bifunctional telechelics is demonstrated under variety of conditions of ATRP and coupling steps.
Ruthenium Ring‐Opening Metathesis Polymerization Catalysts Bearing o‐ Aryloxide‐N‐Heterocyclic Carbenes
Authors: Kong Yong , Tang Yungang , Wang Zunzhi , Xu Shansheng , Song Haibin , Wang Baiquan 
Published: November 2012

AbstractA series of o‐aryloxide‐N‐heterocyclic carbene ruthenium complexes 2–4 is synthesized via sequential reactions of the o‐hydroxyaryl imidazolium proligands (2‐OH‐3,5‐tBu2C6H2)(R)(C3H3N2)+Br− (R = Me (1a), iPr (1b), Mes (1c)) with Ag2O and [(C6H6)RuCl2]2. All of the complexes are characterized by 1H and 13C NMR spectroscopy, high‐resolution mass spectrometry (HRMS), and elemental analysis. The molecular structure of 2 is determined by single‐crystal X‐ray diffraction analysis. The ring‐opening metathesis polymerization (ROMP) of norbornene (NBE) with 2–4 is studied. Among them, complex 4 exhibits the highest activity and efficiency toward ROMP of NBE at 85 °C without any cocatalyst, and the resultant polymers have very high molecular weight (>106 Da) and narrow molecular weight distributions. This complex can also efficiently catalyze the alternating copolymerization of NBE and cyclooctene.
High‐Performance Nanocomposites of Sodium Carboxymethylcellulose and Graphene Oxide
Authors: Layek Rama K. , Kundu Aniruddha , Nandi Arun K. 
Published: November 2012

AbstractHigh‐performance nanocomposites of NaCMC with GO are produced by solution casting. FESEM images reveal a good homogeneous dispersion of GO in the NaCMC matrix. The composite formation is facilitated by H‐bonding interaction between GO and NaCMC. Tg of the composites increases with increasing GO concentration. The storage modulus (G′) exhibits a maximum 174% increase over NaCMC at 1 wt% GO. The mechanical properties of the composites exhibit highest increase of tensile stress and Young's modulus of 188 ± 4% and 154 ± 11%, respectively, for 1 wt% GO. Analysis of Young's modulus (Ey) data using the Halpin‐Tsai equation suggests that the Ey data are close to the unidirectional orientation at >0.5 wt% GO, indicating more efficient load transfer at these compositions. magnified image
Curcumin alleviates oxidative stress, inflammation, and renal fibrosis in remnant kidney through the Nrf2–keap1 pathway
Authors: Soetikno Vivian , Sari Flori R. , Lakshmanan Arun P. , Arumugam Somasundaram , Harima Meilei , Suzuki Kenji , Kawachi Hiroshi , Watanabe Kenichi 
Published: November 2012

ScopeWe hypothesized that curcumin, by increasing the expression of nuclear factor‐erythroid‐2‐related factor 2 (Nrf2), could reduce oxidative stress, inflammation, and renal fibrosis in remnant kidney.Methods and resultsSprague‐Dawley rats were subjected to 5/6 nephrectomy and randomly assigned to untreated (Nx), curcumin‐treated (75 mg/kg/day, orally), and telmisartan‐treated groups (10 mg/kg/day, orally; as positive control). Sham‐operated rats also served as controls. Five/sixth nephrectomy caused renal dysfunction, as evidenced by elevated proteinuria, blood urea nitrogen, and plasma creatinine, and decreased creatinine clearance that were ameliorated by curcumin or telmisartan treatment. The Nx rats demonstrated reduced Nrf2 protein expression, whereas the Kelch‐like ECH‐associated protein 1 was upregulated and heme oxygenase‐1 level was significantly diminished. Consequently, Nx animals had significantly higher kidney malondialdehyde concentration and lower glutathione peroxidase activity, which was associated with the upregulation of nicotinamide adenine dinucleotide phosphatase oxidase subunit (p67phox and p22phox), NF‐kappaB p65, TNF‐α, TGF‐β1, cyclooxygenase‐2, and fibronectin accumulation in remnant kidney. Interestingly, all of these changes were ameliorated by curcumin or telmisartan.ConclusionThese findings demonstrate that, by modulating Nrf2‐Keap1 pathway, the curcumin effectively attenuates oxidative stress, inflammation, and renal fibrosis, which suggest that curcumin hold promising potential for safe treatment of chronic kidney disease.