bluuebunny/crossref_metadata_2025 huggingface dataset:
Ælfric's apostles
Authors: Magennis Hugh
Published: November 2016

New Testament writings give a powerful sense of the humanness and fallibility of Christ's apostles, and a sense of their imperfection is also apparent in the non-canonical acts which report their missionary work and martyrdoms. Ælfric, drawing extensively on this biblical and extra-biblical material, adopts two distinct approaches in his treatment of the apostles, depending on whether he is writing hagiographically or exegetically. In neither approach does he present the apostles as imperfect or fallible, even where they appear so in the sources he is working with. The present article examines Ælfric's manoeuvres in rewriting the apostles as idealized and exemplary figures, focusing in particular on his treatment of Thomas, Peter and Paul in his homilies. In the case of Peter, Ælfric's approach is contrasted tellingly with that of the poet of The Heliand, who stresses the saint's powerful emotions and the personal nature of his relationship to Christ. The article demonstrates Ælfric's anxiety not to undermine the apostles in any way: bringing these great saints to life as struggling human beings is certainly not part of his agenda as religious teacher.
Explaining Anglo-Saxon military efficiency: the landscape of mobilization
Authors: Baker John , Brookes Stuart
Published: November 2016

The importance of warfare in Anglo-Saxon England is widely accepted, but the processes by which armies were put in the field are only partially understood, with most discussion focusing on the economic logistics rather than the spatial practicalities of mobilization. Yet such a system underpinned recorded military actions and must have evolved in response to changing military organization in the late Anglo-Saxon period. Through an assessment of documentary references to sites of muster, and by using a multidisciplinary landscape-focused approach, this article examines possible traces of that system – especially those preserved in place-names – and relates them to later Anglo-Saxon administrative geography.
Affective piety and the practice of penance in late-eleventh-century Worcester: the address to the penitent in Oxford, Bodleian Library, Junius 121
Authors: Forbes Helen Foxhall
Published: November 2016

Oxford, Bodleian Library, Junius 121, a manuscript written in Worcester in the early years of the episcopate of St Wulfstan (1062–95), contains a unique, untitled, anonymous text which has previously been interpreted as a Lenten homily. This article argues that this text is not a homily, but must be understood in the context of the penitential material surrounding it in Junius 121, for which it was probably specifically composed. The text has not attracted much attention, but it is an important early and vernacular witness to the developing tradition of affective writing which became prominent during the latter part of the eleventh century. In addition, the text itself and its placing in its manuscript context reveal the careful, deliberate decisions which Junius 121's compiler made about his material: by reusing earlier texts alongside newly composed English material, he provided practical pastoral and penitential materials for use in late-eleventh-century Worcester.
Psychiatric Disorders and Personality Styles in Mothers of Female Adolescent Patients with Eating Disorders
Authors: Rost Silke , Kappel Viola , Salbach Harriet , Schneider Nora , Pfeiffer Ernst , Lehmkuhl Ulrike , Winter Sibylle , Sarrar Lea
Published: November 2016

Abstract. Objective: To provide further insight into the presently poorly understood role of familial psychopathology in the development of eating disorders (ED). Method: The present study assesses psychiatric and personality disorders listed on Axis I and II of the DSM-IV in 27 mothers of adolescent patients with anorexia (AN mothers) and 14 bulimia nervosa (BN mothers) as well as 22 mentally healthy girls (CG mothers) on a categorical level. Furthermore, we conducted a dimensional diagnostic regarding personality styles and personality traits. Results: AN and BN mothers showed increased rates of Axis I disorders, especially affective, substance use, and anxiety disorders. Differences on Axis II did not reach statistical significance. However, BN mothers showed higher occurrences of paranoid, negativistic, and schizotypal personality styles compared to the other groups. BN mothers further showed higher occurrences than CG mothers of the personality traits excitability, aggressiveness, physical complaints, openness, and emotionality. AN mothers differed significantly from CG mothers on the scale demands. Conclusions: Increased occurrence of psychopathology on both categorical and dimensional levels in mothers of patients with AN and BN supports the assumption of a familial accumulation of psychopathology in ED. Longitudinal studies and genetic analyses should clarify a possible cause-effect relationship and interactions between familial dynamics and adolescent ED.

Keywords: eating disorders, adolescent patients, mothers, psychiatric disorders, personality styles.
Phase retrieval by coherent modulation imaging
Authors: Zhang Fucai , Chen Bo , Morrison Graeme R. , Vila-Comamala Joan , Guizar-Sicairos Manuel , Robinson Ian K.
Published: November 2016

Phase retrieval is a long-standing problem in imaging when only the intensity of the wavefield can be recorded. Coherent diffraction imaging is a lensless technique that uses iterative algorithms to recover amplitude and phase contrast images from diffraction intensity data. For general samples, phase retrieval from a single-diffraction pattern has been an algorithmic and experimental challenge. Here we report a method of phase retrieval that uses a known modulation of the sample exit wave. This coherent modulation imaging method removes inherent ambiguities of coherent diffraction imaging and uses a reliable, rapidly converging iterative algorithm involving three planes. It works for extended samples, does not require tight support for convergence and relaxes dynamic range requirements on the detector. Coherent modulation imaging provides a robust method for imaging in materials and biological science, while its single-shot capability will benefit the investigation of dynamical processes with pulsed sources, such as X-ray free-electron lasers.
Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers
Authors: Pérez-Guijarro Eva , Karras Panagiotis , Cifdaloz Metehan , Martínez-Herranz Raúl , Cañón Estela , Graña Osvaldo , Horcajada-Reales Celia , Alonso-Curbelo Direna , Calvo Tonantzin G. , Gómez-López Gonzalo , Bellora Nicolas , Riveiro-Falkenbach Erica , Ortiz-Romero Pablo L. , Rodríguez-Peralto José L. , Maestre Lorena , Roncador Giovanna , de Agustín Asensio Juan C. , Goding Colin R. , Eyras Eduardo , Megías Diego , Méndez Raúl , Soengas María S.
Published: November 2016

Nuclear 3’-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma.
Interplay between past market correlation structure changes and future volatility outbursts
Authors: Musmeci Nicoló , Aste Tomaso , Di Matteo T.
Published: November 2016

We report significant relations between past changes in the market correlation structure and future changes in the market volatility. This relation is made evident by using a measure of “correlation structure persistence” on correlation-based information filtering networks that quantifies the rate of change of the market dependence structure. We also measured changes in the correlation structure by means of a “metacorrelation” that measures a lagged correlation between correlation matrices computed over different time windows. Both methods show a deep interplay between past changes in correlation structure and future changes in volatility and we demonstrate they can anticipate market risk variations and this can be used to better forecast portfolio risk. Notably, these methods overcome the curse of dimensionality that limits the applicability of traditional econometric tools to portfolios made of a large number of assets. We report on forecasting performances and statistical significance of both methods for two different equity datasets. We also identify an optimal region of parameters in terms of True Positive and False Positive trade-off, through a ROC curve analysis. We find that this forecasting method is robust and it outperforms logistic regression predictors based on past volatility only. Moreover the temporal analysis indicates that methods based on correlation structural persistence are able to adapt to abrupt changes in the market, such as financial crises, more rapidly than methods based on past volatility.
Fluorescence- and magnetic-activated cell sorting strategies to separate spermatozoa involving plural contributors from biological mixtures for human identification
Authors: Xu Yan , Xie Jianhui , Chen Ronghua , Cao Yu , Ping Yuan , Xu Qingwen , Hu Wei , Wu Dan , Gu Lihua , Zhou Huaigu , Chen Xin , Zhao Ziqin , Zhong Jiang , Li Rui
Published: November 2016

No effective method has been developed to distinguish sperm cells originating from different men in multi-suspect sexual assault cases. Here we combined MACS and FACS to isolate single donor sperm cells from forensic mixture samples including female vaginal epithelial cells and sperm cells from multiple contributors. Sperms from vaginal swab were isolated by MACS using FITC-conjugated A kinase anchor protein 3 (AKAP3) antibody; target individual sperm cells involving two or three donors were separated by FACS using FITC-labeled blood group A/B antigen antibody. This procedure was further tested in two mock multi-suspect sexual assault samples and one practical casework sample. Our results showed that complete single donor STR profiles could be successfully obtained from sperm/epithelial cell and sperm mixtures from two contributors. For unbalanced sperm/epithelial cells and sperm cells mixtures, sensitivity results revealed that target cells could be detected at as low as 1:32 and 1:8 mixed ratios, respectively. Although highly relies on cell number and blood types or secretor status of the individuals, this procedure would still be useful tools for forensic DNA analysis of multi-suspect sexual assault cases by the combined use of FACS and MACS based on sperm-specific AKAP3 antigen and human blood type antigen.
miRNAsong: a web-based tool for generation and testing of miRNA sponge constructs in silico
Authors: Barta Tomas , Peskova Lucie , Hampl Ales
Published: November 2016

MicroRNA (miRNA) sponges are RNA transcripts containing multiple high-affinity binding sites that associate with and sequester specific miRNAs to prevent them from interacting with their target messenger (m)RNAs. Due to the high specificity of miRNA sponges and strong inhibition of target miRNAs, these molecules have become increasingly applied in miRNA loss-of-function studies. However, improperly designed sponge constructs may sequester off-target miRNAs; thus, it has become increasingly important to develop a tool for miRNA sponge construct design and testing. In this study, we introducemicroRNA spongegenerator and tester (miRNAsong), a freely available web-based tool for generation andin silicotesting of miRNA sponges. This tool generates miRNA sponge constructs for specific miRNAs and miRNA families/clusters and tests them for potential binding to miRNAs in selected organisms. Currently, miRNAsong allows for testing of sponge constructs in 219 species covering 35,828 miRNA sequences. Furthermore, we also provide an example, supplemented with experimental data, of how to use this tool. Using miRNAsong, we designed and tested a sponge for miR-145 inhibition, and cloned the sequence into an inducible lentiviral vector. We found that established cell lines expressing miR-145 sponge strongly inhibited miR-145, thus demonstrating the usability of miRNAsong tool for sponge generation. URL:http://www.med.muni.cz/histology/miRNAsong/.
Genomic contributors to atrial electroanatomical remodeling and atrial fibrillation progression: Pathway enrichment analysis of GWAS data
Authors: Husser Daniela , Ueberham Laura , Dinov Borislav , Kosiuk Jedrzej , Kornej Jelena , Hindricks Gerhard , Shoemaker M. Benjamin , Roden Dan M. , Bollmann Andreas , Büttner Petra
Published: November 2016

In atrial fibrillation (AF), left atrial diameter (LAD) and low voltage area (LVA) are intermediate phenotypes that are associated with AF type and progression. In this study, we tested the hypothesis, that these phenotypes share common, genetically-determined pathways using pathway enrichment analysis of GWAS data. Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) were genotyped for ~1,000,000 SNPs. SNPs found significantly associated with LAD, LVA or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG). Associated genes were tested for pathway enrichment using two enrichment tools (WebGestalt and GATHER) and the databases provided by Kyoto Encyclopedia of Genes and Genomes. The calcium signaling pathway (hsa04020) was the only pathway that reached statistical significance for LAD and LVA in both enrichment tools and was also significantly associated with AF type. Within this pathway, there were 39 genes (i.e. CACNA1C, RyR2) that were associated with LAD, LVA and AF type. In conclusion, there is a genomic contribution to electroanatomical remodeling (LAD, LVA) and AF type via the calcium signaling pathway. Future and larger studies are necessary to replicate and apply these findings.
Gene expression profiling of breast cancer in Lebanese women
Authors: Makoukji Joelle , Makhoul Nadine J. , Khalil Maya , El-Sitt Sally , Aldin Ehab Saad , Jabbour Mark , Boulos Fouad , Gadaleta Emanuela , Sangaralingam Ajanthah , Chelala Claude , Boustany Rose-Mary , Tfayli Arafat
Published: November 2016

Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer.
Significant Phylogenetic Signal and Climate-Related Trends in Leaf Caloric Value from Tropical to Cold-Temperate Forests
Authors: Song Guangyan , Li Ying , Zhang Jiahui , Li Meiling , Hou Jihua , He Nianpeng
Published: November 2016

Leaf caloric value (LCV) is a useful index to represent the conversion efficiency of leaves for solar energy. We investigated the spatial pattern of LCV and explored the factors (phylogeny, climate, and soil) that influence them at a large scale by determining LCV standardized by leaf area in 920 plant species from nine forest communities along the 3700 km North-South Transect of Eastern China. LCV ranged from 0.024 to 1.056 kJ cm−2 with an average of 0.151 kJ cm−2. LCV declined linearly with increasing latitude along the transect. Altogether, 57.29% of the total variation in LCV was explained by phylogenetic group (44.03% of variation), climate (1.27%), soil (0.02%) and their interacting effects. Significant phylogenetic signals in LCV were observed not only within forest communities but also across the whole transect. This phylogenetic signal was higher at higher latitudes, reflecting latitudinal change in the species composition of forest communities from complex to simple. We inferred that climate influences the spatial pattern of LCV through directly regulating the species composition of plant communities, since most plant species might tolerate only a limited temperature range. Our findings provide new insights into the adaptive mechanisms in plant traits in future studies.
Generalised monogamy relation of convex-roof extended negativity in multi-level systems
Authors: Tian Tian , Luo Yu , Li Yongming
Published: November 2016

In this paper, we investigate the generalised monogamy inequalities of convex-roof extended negativity (CREN) in multi-level systems. The generalised monogamy inequalities provide the upper and lower bounds of bipartite entanglement, which are obtained by using CREN and the CREN of assistance (CRENOA). Furthermore, we show that the CREN of multi-qubit pure states satisfies some monogamy relations. Additionally, we test the generalised monogamy inequalities for qudits by considering the partially coherent superposition of a generalised W-class state in a vacuum and show that the generalised monogamy inequalities are satisfied in this case as well.
Managing peatland vegetation for drinking water treatment
Authors: Ritson Jonathan P. , Bell Michael , Brazier Richard E. , Grand-Clement Emilie , Graham Nigel J. D. , Freeman Chris , Smith David , Templeton Michael R. , Clark Joanna M.
Published: November 2016

Peatland ecosystem services include drinking water provision, flood mitigation, habitat provision and carbon sequestration. Dissolved organic carbon (DOC) removal is a key treatment process for the supply of potable water downstream from peat-dominated catchments. A transition from peat-forming Sphagnum moss to vascular plants has been observed in peatlands degraded by (a) land management, (b) atmospheric deposition and (c) climate change. Here within we show that the presence of vascular plants with higher annual above-ground biomass production leads to a seasonal addition of labile plant material into the peatland ecosystem as litter recalcitrance is lower. The net effect will be a smaller litter carbon pool due to higher rates of decomposition, and a greater seasonal pattern of DOC flux. Conventional water treatment involving coagulation-flocculation-sedimentation may be impeded by vascular plant-derived DOC. It has been shown that vascular plant-derived DOC is more difficult to remove via these methods than DOC derived from Sphagnum, whilst also being less susceptible to microbial mineralisation before reaching the treatment works. These results provide evidence that practices aimed at re-establishing Sphagnum moss on degraded peatlands could reduce costs and improve efficacy at water treatment works, offering an alternative to ‘end-of-pipe’ solutions through management of ecosystem service provision.
Endotoxemia contributes to CD27+ memory B-cell apoptosis via enhanced sensitivity to Fas ligation in patients with Cirrhosis
Authors: Chang Li-Yuan , Li Yonghai , Kaplan David E.
Published: November 2016

Peripheral CD27+ memory B-cells become quantitatively reduced and dysfunctional in patients with cirrhosis through poorly characterized mechanisms. We hypothesized that the disappearance of CD27+ memory B-cells results from enhanced sensitivity to apoptosis caused by exposure to gut microbial translocation products. Using isolated naïve and memory B-cells from patients with cirrhosis and age-matched controls, ex vivo and activation-induced sensitivity to Fas-mediated apoptosis was assessed under relevant experimental conditions. We observed differential expression of CD95(Fas) in CD27+ B-cells from cirrhotic patients that was inversely correlated with peripheral CD27+ B-cell frequency. While memory B-cells from cirrhotic patients were resistant to Fas-mediated apoptosis ex vivo, Toll-like receptor 4(TLR4)-ligation restored Fas-sensitivity. Sensitivity to Fas-mediated apoptosis could be transferred to healthy donor memory B-cells by co-culturing these cells with plasma from cirrhotic patients, a sensitivity partially mediated by Fas and TLR4 signaling, and partially rescued via B-cell receptor crosslinking. We conclude that peripheral CD27+ memory B-cells in cirrhosis exhibit increased sensitivity to Fas-induced apoptosis in an activation-dependent manner to which endotoxin contributes, associated with reduced frequency of circulating memory B-cells. Destruction of this critical cell subset may contribute to the cirrhotic immunodeficiency state and heightened risk of systemic infections in advanced liver disease.
Dramatic undercutting of piedmont rivers after the 2008 Wenchuan Ms 8.0 Earthquake
Authors: Fan Niannian , Nie Ruihua , Wang Qiang , Liu Xingnian
Published: November 2016

Changes in river channel erosion or deposition affect the geomorphic evolution, aquatic ecosystems, and river regulation strategies. Fluvial processes are determined by the flow, sediment and boundary conditions, and it has long been expected that increasing sediment supply will induce aggradation. Here, based on thorough field surveys, we show the unexpected undercutting of the piedmont rivers influenced by the 2008 Wenchuan (Ms 8.0) Earthquake. The rivers flow from the Longmen Mountain with significant topographic relief to the flat Chengdu plain. In the upstreams, sediment supply increased because of the landslides triggered by the earthquake, causing deposition in the upstream mountain reaches. However, the downstream plain reaches suffered undercutting instead of deposition, and among those rivers, Shiting River was the most seriously affected, with the largest undercutting depth exceeding 20 m. The reasons for this unexpected undercutting are proposed herein and relate to both natural and anthropogenic causes. In addition, we also demonstrate, at least for certain conditions, such as rivers flowing from large-gradient mountain regions to low-gradient plain regions, that upstream sediment pulses may induce aggradation in upstream and degradation in downstream, causing the longitudinal profile to steepen to accommodate the increasing sediment flux.
Stent revascularization versus bypass surgery for peripheral artery disease in type 2 diabetic patients – an instrumental variable analysis
Authors: Chang Chia-Hsuin , Lin Jou-Wei , Hsu Jiun , Wu Li-Chiu , Lai Mei-Shu
Published: November 2016

The objective of this study was to use instrumental variable (IV) analyses to evaluate the clinical effectiveness of percutaneous stent revascularization versus bypass surgery in the treatment of peripheral artery disease (PAD) among type 2 diabetic patients. Type 2 diabetic patients who received peripheral artery bypass surgery (n = 5,652) or stent revascularization (n = 659) for lower extremity arterial stenosis between 2000 and 2007 were identified from the Taiwan National Health Insurance claims database. Patients were followed from the date of index hospitalization for 2 years for lower-extremity amputation, revascularization, and hospitalization for medical treatment. Analysis using treatment year, patients’ monthly income level, and regional difference as IVs were conducted to reduce unobserved treatment selection bias. The crude analysis showed a statistically significant risk reduction in favor of stent placement in lower extremity amputation and in the composite endpoint of amputation, revascularization, or hospitalization for medical treatment. However, peripheral artery stent revascularization and bypass surgery had similar risk of lower limb amputation and composite endpoints in the analyses using calendar year or patients’ monthly income level as IVs. These two treatment modalities had similar risk of lower limb amputation among DM patients with PAD.
Laser controlled atom source for optical clocks
Authors: Kock Ole , He Wei , Świerad Dariusz , Smith Lyndsie , Hughes Joshua , Bongs Kai , Singh Yeshpal
Published: November 2016

Precision timekeeping has been a driving force in innovation, from defining agricultural seasons to atomic clocks enabling satellite navigation, broadband communication and high-speed trading. We are on the verge of a revolution in atomic timekeeping, where optical clocks promise an over thousand-fold improvement in stability and accuracy. However, complex setups and sensitivity to thermal radiation pose limitations to progress. Here we report on an atom source for a strontium optical lattice clock which circumvents these limitations. We demonstrate fast (sub 100 ms), cold and controlled emission of strontium atomic vapours from bulk strontium oxide irradiated by a simple low power diode laser. Our results demonstrate that millions of strontium atoms from the vapour can be captured in a magneto-optical trap (MOT). Our method enables over an order of magnitude reduction in scale of the apparatus. Future applications range from satellite clocks testing general relativity to portable clocks for inertial navigation systems and relativistic geodesy.
Giant frequency down-conversion of the dancing acoustic bubble
Authors: Deymier P. A. , Keswani M. , Jenkins N. , Tang C. , Runge K.
Published: November 2016

We have demonstrated experimentally the existence of a giant frequency down-conversion of the translational oscillatory motion of individual submillimeter acoustic bubbles in water in the presence of a high frequency (500 kHz) ultrasonic standing wave. The frequency of the translational oscillations (~170 Hz) is more than three orders of magnitude smaller than that of the driving acoustic wave. We elucidate the mechanism of this very slow oscillation with an analytical model leading to an equation of translational motion of a bubble taking the form of Mathieu’s equation. This equation illuminates the origin of the giant down conversion in frequency as arising from an unstable equilibrium. We also show that bubbles that form chains along the direction of the acoustic standing wave due to radiation interaction forces exhibit also translation oscillations that form a spectral band. This band extends approximately from 130 Hz up to nearly 370 Hz, a frequency range that is still at least three orders of magnitude lower than the frequency of the driving acoustic wave.
Elevated Mitochondrial DNA Copy Number in Peripheral Blood and Tissue Predict the Opposite Outcome of Cancer: A Meta-Analysis
Authors: Chen Nan , Wen Shu , Sun Xiaoru , Fang Qian , Huang Lin , Liu Shuai , Li Wanling , Qiu Meng
Published: November 2016

Previous studies have suggested that mitochondrial DNA (mtDNA) copy number was associated with cancer risk. However, no solid conclusion revealed the potential predictive value of mtDNA copy number for cancer prognosis. The present meta-analysis was performed to clarify the problem. Hence, we performed a systematic search in PubMed, EmBase, Web of Science databases independently and a total of eighteen studies comprising 3961 cases satisfied the criteria and finally enrolled. Our results didn’t show the association between them but significant heterogeneity in overall analysis (OS: HR = 0.923, 95% CI: 0.653–1.306, p = 0.652; DFS: HR = 0.997, 95% CI: 0.599–1.659, p = 0.99). However, subgroup analysis stratified by sample came to the opposite conclusion. High level mitochondrial DNA copy number in peripheral blood predicted a poor cancer prognosis (OS: HR = 1.624, 95% CI: 1.211–2.177, p = 0.001; DFS: HR = 1.582, 95% CI: 1.026–2.439, p = 0.038) while patients with high level mitochondrial DNA copy number in tumor tissue exhibited better outcomes (OS: HR = 0.604 95% CI: 0.406–0.899, p = 0.013; DFS: HR = 0.593, 95% CI: 0.411–0.857, p = 0.005). These findings were further proved in detailed analyses in blood or tissue subgroup. In conclusion, our study suggested the elevated mtDNA copy number in peripheral blood predicted a poor cancer prognosis while the better outcome was presented among patients with elevated mtDNA copy number in tumor tissue.
Non-High-Density Lipoprotein Cholesterol Levels on the Risk of Asymptomatic Intracranial Arterial Stenosis: A Result from the APAC Study
Authors: Wu Jianwei , Wang Anxin , Li Xin , Wu Shouling , Zhao Xingquan
Published: November 2016

Intracranial arterial stenosis (ICAS) is an important cause of ischemic stroke and transient ischemic attack (TIA), and the correlation between the plasma non-high density cholesterol (non-HDLC) levels and ICAS, especially asymptomatic ICAS (AICAS) is not clear. The Asymptomatic Polyvascular Abnormalities Community(APAC) study is a community-based, prospective, long-term follow-up observational study. 3387 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 3 groups based on their non-HDLC levels. The cox regression was used to analyze the correlation between the non-HDLC level and the incidence of AICAS.9.98% of the participants were diagnosed with AICAS during 2 years following up. Multivariate analysis showed that non-HDL-C is an independent indicator for the incidence of AICAS (HR = 1.22, 95%CI: 1.06–1.40), The incidence of AICAS gradually increase with the increasing non-HDLC level. Compared with subgroup(non-HDLC < 3.4 mmol/l), incidence of AICAS was significantly higher in the subgroups(non-HDLC 3.4–4.1 mmol/l and non-HDLC ≥ 4.1 mmol/l) after adjustment for the confounding factors (HR = 1.32, 95%CI:1.02–1.73; HR = 1.46, 95%CI: 1.10–1.94, respectively). In conclusions, our findings suggest that elevated non-HDLC levels a significant risk factor for the development of AICAS in the APAC study.
Tet1-dependent epigenetic modification of BDNF expression in dorsal horn neurons mediates neuropathic pain in rats
Authors: Hsieh Ming-Chun , Lai Cheng-Yuan , Ho Yu-Cheng , Wang Hsueh-Hsiao , Cheng Jen-Kun , Chau Yat-Pang , Peng Hsien-Yu
Published: November 2016

Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), hence promoting DNA demethylation. Although recent studies have linked the DNA demethylation of specific genes to pain hypersensitivity, the role of spinal Tet1-dependent DNA demethylation in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, spinal nerve ligation (SNL) upregulated Tet1 expression in dorsal horn neurons that hydroxylate 5 mC to 5 hmC at CpG dinucleotides in the bdnf promoter to promote spinal BDNF expression at day 7 after operation. Focal knockdown of spinal Tet1 expression decreased Tet1 binding and 5 hmC enrichment, further increased 5 mC enrichment at CpG sites in the bdnf promoter and decreased spinal BDNF expression accompanied by the alleviation of the developed allodynia. Moreover, at day 7 after operation, SNL-enhanced Tet1 expression also inhibited the binding of DNA methyltransferases (DNMTs, i.e., DNMT1, DNMT3a, and DNMT3b) to the bdnf promoter, a requirement for transcriptional silencing by catalysing 5-cytosine (5C) to 5 mC. Together, these data suggest at CpG sites of the bdnf promoter, SNL-enhanced Tet1 expression promotes DNA demethylation both by converting 5 mC to 5 hmC and inhibiting DNMT binding to regulate spinal BDNF expression, hence contributing to behavioral allodynia development.
The Modification of Tet1 in Male Germline Stem Cells and Interact with PCNA, HDAC1 to promote their Self-renewal and Proliferation
Authors: Zheng Liming , Zhai Yuanxin , Li Na , Ma Fanglin , Zhu Haijing , Du Xiaomin , Li Guangpeng , Hua Jinlian
Published: November 2016

Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock. In our study, we not only analyzed the morphology, gene expression, DNA methylation and histone methylation dynamic in mouse Tet1 (mTet1) modified mGSCs, we also analyzed the stemness ability by in vivo transplantation and explored the functional mechanism of Tet1 in dairy goat mGSCs. The results showed mTet1 modified mGSCs had better self-renewal and proliferation ability than wild-type mGSCs, mTet1 could also up-regulate JMJD3 to decrease H3K27me3, which also showed to suppress the MEK-ERK pathway. Furthermore, Co-IP analysis demonstrated that TET1 interact with PCNA and HDAC1 by forming protein complexes to comprehensively regulate dairy goat mGSCs and spermatogenesis.
miR-96 promotes cell proliferation, migration and invasion by targeting PTPN9 in breast cancer
Authors: Hong Yeting , Liang Hongwei , Uzair-ur-Rehman  , Wang Yanbo , Zhang Weijie , Zhou Yong , Chen Song’an , Yu Mengchao , Cui Sufang , Liu Minghui , Wang Nan , Ye Chao , Zhao Chihao , Liu Yanqing , Fan Qian , Zhang Chen-Yu , Sang Jianfeng , Zen Ke , Chen Xi
Published: November 2016

microRNAs (miRNAs) have emerged as major regulators of the initiation and progression of human cancers, including breast cancer. The aim of this study is to determine the expression pattern of miR-96 in breast cancer and to investigate its biological role during tumorigenesis. We showed that miR-96 was significantly upregulated in breast cancer. We then investigated its function and found that miR-96 significantly promoted cell proliferation, migration and invasion in vitro and enhanced tumor growth in vivo. Furthermore, we explored the molecular mechanisms by which miR-96 contributes to breast cancer progression and identified PTPN9 (protein tyrosine phosphatase, non-receptor type 9) as a direct target gene of miR-96. Finally, we showed that PTPN9 had opposite effects to those of miR-96 on breast cancer cells, suggesting that miR-96 may promote breast tumorigenesis by silencing PTPN9. Taken together, this study highlights an important role for miR-96 in the regulation of PTPN9 in breast cancer cells and may provide insight into the molecular mechanisms of breast carcinogenesis.
Electronic structure of organometal halide perovskite CH3NH3BiI3 and optical absorption extending to infrared region
Authors: Zhu H. X. , Liu J.-M.
Published: November 2016

The electronic structure and optical absorption spectrum of organometal halide perovskite compound CH3NH3BiI3 as a substituting candidate of well-concerned CH3NH3PbI3 not only for environmental friendly consideration are studied using the first principles calculations. It is revealed that a Bi replacement of Pb in CH3NH3PbI3 does not change seriously the band edge structure but the bandgap becomes narrow. Consequently, CH3NH3BiI3 exhibits not only stronger visible light absorption than CH3NH3PbI3 does but more strong absorption in the infrared region, which is however absent in CH3NH3PbI3. It is suggested that CH3NH3BiI3 may be one of even more promising alternatives to CH3NH3PbI3 for spectrum-broad and highly-efficient solar cells.
Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease
Authors: Wang Xianli , Dong Chuanming , Sun Lixin , Zhu Liang , Sun Chenxi , Ma Rongjie , Ning ke , Lu Bing , Zhang Jinfu , Xu Jun
Published: November 2016

Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines. Furthermore, quantitative proteomics and ingenuity pathway analysis were used to evaluate the significant age-related alterations in proteins and their functions. Some downregulated proteins such as DPYSL2, TPI1, ALDH, and UCHL1 were found to play critical roles in the neurological disease and PSMA1, PSMA3, PSMC2, PSMD11, and UCHL1 in protein homeostasis. Taken together, we have provided valuable insight into the cellular and molecular processes that underlie aging-associated declines in SVZ neurogenesis for the early detection of differences in gene expression and the potential risk of neurological disease, which is beneficial in the prevention of the diseases.
A Nonparametric Regression Approach to Control for Population Stratification in Rare Variant Association Studies
Authors: Sha Qiuying , Zhang Kui , Zhang Shuanglin
Published: November 2016

Recently, there is increasing interest to detect associations between rare variants and complex traits. Rare variant association studies usually need large sample sizes due to the rarity of the variants, and large sample sizes typically require combining information from different geographic locations within and across countries. Although several statistical methods have been developed to control for population stratification in common variant association studies, these methods are not necessarily controlling for population stratification in rare variant association studies. Thus, new statistical methods that can control for population stratification in rare variant association studies are needed. In this article, we propose a principal component based nonparametric regression (PC-nonp) approach to control for population stratification in rare variant association studies. Our simulations show that the proposed PC-nonp can control for population stratification well in all scenarios, while existing methods cannot control for population stratification at least in some scenarios. Simulations also show that PC-nonp’s robustness to population stratification will not reduce power. Furthermore, we illustrate our proposed method by using whole genome sequencing data from genetic analysis workshop 18 (GAW18).
Fabrication, Characterization and Response Surface Method (RSM) Optimization for Tetracycline Photodegration by Bi3.84W0.16O6.24- graphene oxide (BWO-GO)
Authors: Song Chengjie , Li Xinying , Wang Liping , Shi Weidong
Published: November 2016

RSM is a powerful tool for optimizing photocatalytic processes. The BWO-GO photocatalysts have been successfully synthesized via inorganic-salt-assisted hydrothermal method. XRD, TEM, FESEM, HRTEM and STEM are used to characterize BWO-GO heterojunction. UV-vis, PL, ESR and radical scavenger experiments are used to explore the photocatalysis mechanism. The photocatalysts are evaluated by TC photodegradation under visible light irradiation. And the main active species in TC photodegradation is ·O2−. Response surface methodology is used to optimize three key independent operating parameters, namely photocatalyst dosage (X1), percentages of GO (X2) and reaction time (X3), for TC photodegradation. The central composite design (CCD) is used to conduct experiments. The results showed that TC removal is significantly affected by the synergistic effect of linear term of X1 and X3. However, the quadratic terms of X12 and X32 had an antagonistic effect on T removal. The obtained RSM model (R2 = 0.9206) shows a satisfactory correlation between experimental and predicted values of TC removal. The optimized conditions is of 0.3 g photocatalyst dosage, 1.49 wt% GO loaded percentage and 90 min reaction time. Under this condition, theoretical prediction removal is 80.22% and the actual removal is 78.43%.
Dopamine regulates renal osmoregulation during hyposaline stress via DRD1 in the spotted scat (Scatophagus argus)
Authors: Su Maoliang , Mu Xingjiang , Gui Lang , Zhang Peipei , Zhou Jianan , Ma Jie , Zhang Junbin
Published: November 2016

Dopamine is an important regulator of renal natriuresis and is critical for the adaptation of many animals to changing environmental salinity. However, the molecular mechanisms through which dopamine promotes this adaptation remain poorly understood. We studied the effects of dopamine on renal hypo-osmoregulation in the euryhaline fish Scatophagus argus (S. argus) during abrupt transfer from seawater (SW) to freshwater (FW). Following the transfer, serum dopamine concentration was decreased, and dopamine activated expression of the dopamine receptor 1 (designated SaDRD1) in the kidney, triggering the osmoregulatory signaling cascade. SaDRD1 protein is expressed in the renal proximal tubule cells in vivo, and is localized to the cell membrane of renal primary cells in vitro. Knockdown of SaDRD1 mRNA by siRNA significantly increased Na+/K+-ATPase (NKA) activity in cultured renal primary cells in vitro, suggesting that expression of SaDRD1 may oppose the activity of NKA. We demonstrate that exogenous dopamine enhances the response of NKA to hyposaline stress after transferring primary renal cells from isosmotic medium to hypoosmotic medium. Our results indicate that dopamine regulation via SaDRD1 ignited the renal dopaminergic system to balance the osmotic pressure through inhibiting NKA activity, providing a new perspective on the hyposaline adaptation of fish.
Targeting Catalytic and Non-Catalytic Functions of Protein Kinases
Authors: Müller Susanne , Knapp Stefan
Published: November 2016

Protein kinases have developed into a major target family for the development of novel therapeutics. With currently more than 30 approved drugs and several hundred ongoing clinical studies, the kinase family has emerged as one of the most successful and established target families. The high degree of structural plasticity of the kinase catalytic domain revealed a multitude of diverse and sometimes target-specific cavities and binding modes, which has enabled the development of highly specific inhibitors. However, recent studies revealed additional essential non-catalytic functions of protein kinases usually associated with the kinase active state. Thus, allosteric kinase inhibitors that stabilize a variety of kinase inactive states modulating both catalytic as well as non-catalytic kinase functions, result in different cellular responses and clinical outcomes when compared with ATP competitive inhibitors that target the active state. These findings indicate that allosteric inhibitors could also be developed targeting scaffolding functions of catalytically inert pseudokinases that often play key roles in disease development. Here we review the main inhibitor classes that have been developed to date and the structural and functional consequences of their distinct binding modes to the kinase catalytic domain.
Muscarinic Receptors Allosteric Modulation
Authors: Melancon Bruce J. , Hopkins Corey R.
Published: November 2016

This chapter describes recent activity in the advancement of ligands and therapeutic lead compounds for the allosteric modulation of the muscarinic receptors and their potential utility as therapies for central nervous system (CNS) disorders. The chapter reviews the activity over the past five years of allosteric modulation of the muscarinic receptor subtypes M1 and M4, along with giving a brief overview of the M5 subtype. Due to concerns about off-target effects and toxicity with orthosteric modulators, much attention has concentrated on positive and negative allosteric modulators of these receptors in order to identify more selective lead compounds. Recent efforts have afforded a variety of improvements in potency and selectivity and pharmacokinetic properties that warrant further investigation and optimization.
Mechanism of Action of a GluN2C- and GluN2D-Selective NMDA Receptor Positive Allosteric Modulator
Authors: Strong Katie L. , Epplin Matthew P. , Jing Yao , Traynelis Stephen F. , Liotta Dennis C.
Published: November 2016

The N-methyl-d-aspartate (NMDA) receptor, fundamental for excitatory synaptic transmission, is a tetrameric assembly of two glycine-binding GluN1 subunits and two glutamate-binding GluN2 subunits, of which there are four subtypes (referred to as GluN2A–GluN2D). The GluN2 subunit endows the receptor with unique pharmacological properties and shows distinct developmental and regional expression profiles, which have led to interest in GluN2-selective modulators for the receptor. One recently described compound, (3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone (referred to as CIQ), selectively potentiates the response of GluN2C- and GluN2D-containing NMDA receptors to agonist activation. This tetrahydroisoquinoline compound has no agonist activity on its own, and is without effect on GluN2A- and GluN2B-containing NMDA receptors. CIQ was the first positive allosteric modulator for the GluN2C and GluN2D subunits reported in the literature, and since its discovery, multiple investigations have provided insight into its mechanism, site of action, pharmacokinetic properties, and off-target activity. CIQ has also been utilized as a tool compound in animal models of fear learning, schizophrenia, and Parkinson’s disease. The compound is being used to elucidate the role of NMDA receptors in these diseases states and to demonstrate the potential therapeutic benefits of a NMDA receptor positive allosteric modulator.
Synthesis of precipitating chromogenic/fluorogenic β-glucosidase/β-galactosidase substrates by a new method and their application in the visual detection of foodborne pathogenic bacteria
Authors: Wei Xianhu , Wu Qingping , Zhang Jumei , Zhang Youxiong , Guo Weipeng , Chen Moutong , Gu Qihui , Cai Zhihe , Lu Mianfei
Published: November 2016

Some indoxyl β-glycosides and novel precipitating fluorogenic β-glucosides were synthesized by a new efficient method and applied for detecting bacteria.
Energetics of CO oxidation on lanthanide-free perovskite systems: the case of Co-doped SrTiO3
Authors: Carlotto Silvia , Natile Marta Maria , Glisenti Antonella , Paul Jean-François , Blanck Dimitri , Vittadini Andrea
Published: November 2016

The energetics of the catalytic oxidation of CO on a complex metal oxide are investigated for the first time via density functional theory calculations.
First-principles calculations of the electronic structure and bonding in metal cluster–fullerene materials considered within the superatomic framework
Authors: Hammerschmidt Lukas , Schacht Julia , Gaston Nicola
Published: November 2016

Inspired by recent experiments, we address the question to what extent the three materials [Co6Se8(PEt3)6][C60]2, [Cr6Se8(PEt3)6][C60]2, and [Ni9Te6(PEt3)8]C60, upon forming compounds, imitate atomic analogues.