bluuebunny/crossref_metadata_2025_split huggingface dataset:
An aposymbiotic primary coral polyp counteracts acidification by active pH regulation
Authors: Ohno Yoshikazu , Iguchi Akira , Shinzato Chuya , Inoue Mayuri , Suzuki Atsushi , Sakai Kazuhiko , Nakamura Takashi 
Published: January 2017

AbstractCorals build their skeletons using extracellular calcifying fluid located in the tissue–skeleton interface. However, the mechanism by which corals control the transport of calcium and other ions from seawater and the mechanism of constant alkalization of calcifying fluid are largely unknown. To address these questions, we performed direct pH imaging at calcification sites (subcalicoblastic medium, SCM) to visualize active pH upregulation in live aposymbiotic primary coral polyps treated with HCl-acidified seawater. Active alkalization was observed in all individuals using vital staining method while the movement of HPTS and Alexa Fluor to SCM suggests that certain ions such as H+ could diffuse via a paracellular pathway to SCM. Among them, we discovered acid-induced oscillations in the pH of SCM (pHSCM), observed in 24% of polyps examined. In addition, we discovered acid-induced pH up-regulation waves in 21% of polyps examined, which propagated among SCMs after exposure to acidified seawater. Our results showed that corals can regulate pHSCM more dynamically than was previously believed. These observations will have important implications for determining how corals regulate pHSCM during calcification. We propose that corals can sense ambient seawater pH via their innate pH-sensitive systems and regulate pHSCM using several unknown pH-regulating ion transporters that coordinate with multicellular signaling occurring in coral tissue.
Targeting the PI3K/AKT pathway via GLI1 inhibition enhanced the drug sensitivity of acute myeloid leukemia cells
Authors: Liang Hui , Zheng Qi-Li , Fang Peng , Zhang Jian , Zhang Tuo , Liu Wei , Guo Min , Robinson Christopher L. , Chen Shui-bing , Chen Xiao-Ping , Chen Fang-Ping , Zeng Hui 
Published: January 2017

AbstractCombination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR. Overexpression of GLI1 in AML cells led to increased AKT phosphorylation and decreased drug sensitivity, which was attenuated by GLI1 inhibition. By contrast, neither the expression of GLI1 nor apoptosis in response to Ara-C treatment of AML cells was significantly affected by PI3K inhibition. Furthermore, co-inhibition of GLI1 and PI3K induced apoptosis of hematopoietic stem/progenitor cells (HSPCs), which raised serious concerns about the side effects of this treatment. These results indicated that GLI1 inhibition alone, but not combined inhibition, is sufficient to enhance AML drug sensitivity, which provides a novel therapeutic strategy for AML treatment.
Comorbid generalized anxiety disorder and its association with quality of life in patients with major depressive disorder
Authors: Zhou Yongjie , Cao Zhongqiang , Yang Mei , Xi Xiaoyan , Guo Yiyang , Fang Maosheng , Cheng Lijuan , Du Yukai 
Published: January 2017

AbstractThe comorbidity of major depressive disorder (MDD) and generalized anxiety disorder (GAD) is common and often predicts poorer outcomes than either disorder alone. This study aimed to examine the prevalence of comorbid GAD and its association with quality of life (QOL) among MDD patients. A total of 1225 psychiatric outpatients were screened using the Hospital Anxiety and Depression Scale (HADS). Those who scored ≥8 on the HADS were interviewed using DSM-IV criteria by two senior psychiatrists. Patients diagnosed with MDD were further assessed using the 9-item Patient Health Questionnaire, Social Support Rating Scale, Pittsburgh Sleep Quality Index, and World Health Organization QOL Scale, brief version (WHOQOL-BREF). Ultimately, 667 patients were diagnosed with MDD, of 71.7% of whom had GAD. Compared to those with MDD alone, comorbid patients had lower scores on the physical (38.64 ± 10.35 vs.36.54 ± 12.32, P = 0.026) and psychological (35.54 ± 12.98 vs. 30.61 ± 14.66, P < 0.001) domains of the WHOQOL-BREF. The association between comorbid GAD and poor QOL on the two domains remained statistically significant in the multiple linear regression (unstandardized coefficients: −1.97 and −4.65, P < 0.001). In conclusion, the prevalence of comorbid GAD in MDD patients is high, and co-occurring GAD may exacerbate impaired physical and psychological QOL in Chinese MDD patients.
An extended N-H bond, driven by a conserved second-order interaction, orients the flavin N5 orbital in cholesterol oxidase
Authors: Golden Emily , Yu Li-Juan , Meilleur Flora , Blakeley Matthew P. , Duff Anthony P. , Karton Amir , Vrielink Alice 
Published: January 2017

AbstractThe protein microenvironment surrounding the flavin cofactor in flavoenzymes is key to the efficiency and diversity of reactions catalysed by this class of enzymes. X-ray diffraction structures of oxidoreductase flavoenzymes have revealed recurrent features which facilitate catalysis, such as a hydrogen bond between a main chain nitrogen atom and the flavin redox center (N5). A neutron diffraction study of cholesterol oxidase has revealed an unusual elongated main chain nitrogen to hydrogen bond distance positioning the hydrogen atom towards the flavin N5 reactive center. Investigation of the structural features which could cause such an unusual occurrence revealed a positively charged lysine side chain, conserved in other flavin mediated oxidoreductases, in a second shell away from the FAD cofactor acting to polarize the peptide bond through interaction with the carbonyl oxygen atom. Double-hybrid density functional theory calculations confirm that this electrostatic arrangement affects the N-H bond length in the region of the flavin reactive center. We propose a novel second-order partial-charge interaction network which enables the correct orientation of the hydride receiving orbital of N5. The implications of these observations for flavin mediated redox chemistry are discussed.
Inferring Centrality from Network Snapshots
Authors: Shao Haibin , Mesbahi Mehran , Li Dewei , Xi Yugeng 
Published: January 2017

AbstractThe topology and dynamics of a complex network shape its functionality. However, the topologies of many large-scale networks are either unavailable or incomplete. Without the explicit knowledge of network topology, we show how the data generated from the network dynamics can be utilised to infer the tempo centrality, which is proposed to quantify the influence of nodes in a consensus network. We show that the tempo centrality can be used to construct an accurate estimate of both the propagation rate of influence exerted on consensus networks and the Kirchhoff index of the underlying graph. Moreover, the tempo centrality also encodes the disturbance rejection of nodes in a consensus network. Our findings provide an approach to infer the performance of a consensus network from its temporal data.
Metallurgical investigation on fourth century BCE silver jewellery of two hoards from Samaria
Authors: Ashkenazi D. , Gitler H. , Stern A. , Tal O. 
Published: January 2017

AbstractA fourth century BCE silver jewellery collection, which is part of two hoards of Samarian coins (the Samaria and Nablus Hoards), was studied by non-destructive analyses. The collection, which consists of pendants, rings, beads and earrings, had been examined by visual testing, multi-focal microscopy and SEM-EDS analysis. In order to enhance our knowledge of past technologies of silver jewellery production, we developed a metallurgical methodology based on the chemical composition of the joints and bulk. The results show that all artefacts are made of silver containing a small percentage of copper. Higher copper concentrations were measured in the joining regions. Our research indicates that the manufacturing of the jewellery from both hoards involved similar techniques, including casting, cutting, hammering, bending, granulating and joining methods, indicating that the artefacts were made by trained silversmiths. Although the burial date of the Samaria Hoard – 352 BCE – is some 21 years earlier than that of the Nablus Hoard – circa 331 BCE, a noted continuity in the local production technology is apparent in the analysed items. This information provides better understanding of the technological abilities in the late Persian-period province of Samaria and bears implications on the local silver coins produced in the region.
IFN-γ regulates human dental pulp stem cells behavior via NF-κB and MAPK signaling
Authors: He Xinyao , Jiang Wenkai , Luo Zhirong , Qu Tiejun , Wang Zhihua , Liu Ningning , Zhang Yaqing , Cooper Paul R. , He Wenxi 
Published: January 2017

AbstractDuring caries, dental pulp expresses a range of pro-inflammatory cytokines in response to the infectious challenge. Interferon gamma (IFN-γ) is a dimerized soluble cytokine, which is critical for immune responses. Previous study has demonstrated that IFN-γ at relative high concentration (100 ng/mL) treatment improved the impaired dentinogenic and immunosuppressive regulatory functions of disease-derived dental pulp stem cells (DPSCs). However, little is known about the regulatory effects of IFN-γ at relative low concentration on healthy DPSC behavior (including proliferation, migration, and multiple-potential differentiation). Here we demonstrate that IFN-γ at relatively low concentrations (0.5 ng/mL) promoted the proliferation and migration of DPSCs, but abrogated odonto/osteogenic differentiation. Additionally, we identified that NF-κB and MAPK signaling pathways are both involved in the process of IFN-γ-regulated odonto/osteogenic differentiation of DPSCs. DPSCs treated with IFN-γ and supplemented with pyrrolidine dithiocarbamate (PDTC, an NF-κB inhibitor) or SB203580 (a MAPK inhibitor) showed significantly improved potential for odonto/osteogenic differentiation of DPSCs both in vivo and in vitro. These data provide important insight into the regulatory effects of IFN-γ on the biological behavior of DPSCs and indicate a promising therapeutic strategy for dentin/pulp tissue engineering in future endodontic treatment.
Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase
Authors: Yu He-Lin , Jiang Shu-Heng , Bu Xu-Liang , Wang Jia-Hua , Weng Jing-Yi , Yang Xiao-Mei , He Kun-Yan , Zhang Zhi-Gang , Ao Ping , Xu Jun , Xu Min-Juan 
Published: January 2017

AbstractPolycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds—ikarugamycin (1), capsimycin (2) and capsimycin B (3)—two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, have been identified. The absolute configurations of the tert/tert-diols moiety was determined in 4 by NMR spectroscopic analysis, CD spectral comparisons and semi-synthetic method. The post-modification mechanism of the carbocyclic ring at C-14/C-13 of compound 1 in the biosynthesis of an important intermediate 3 was investigated. A putative cytochrome P450 superfamily gene, SXIM_40690 (ikaD), which was proximally localized to the ikarugamycin biosynthetic pathway, was characterized. In vivo gene inactivation and complementation experiment confirmed that IkaD catalysed the epoxide-ring formation reaction and further hydroxylation of ethyl side chain to form capsimycin G (3′). Binding affinities and kinetic parameters for the interactions between ikarugamycin (1) and capsimycin B (3) with IkaD were measured with Surface Plasmon Resonance. The intermediate compound 3′ was isolated and identified as 30-hydroxyl-capsimycin B. The caspimycins 2 and 3, were transferred to methoxyl derivatives, 6 and 7, under acidic and heating conditions. Compounds 1–3 exhibited anti-proliferative activities against pancreatic carcinoma with IC50 values of 1.30–3.37 μM.
Global identification of microRNAs associated with chlorantraniliprole resistance in diamondback moth Plutella xylostella (L.)
Authors: Zhu Bin , Li Xiuxia , Liu Ying , Gao Xiwu , Liang Pei 
Published: January 2017

AbstractThe diamondback moth (DBM), Plutella xylostella (L.), is one of the most serious cruciferous pests and has developed high resistance to most insecticides, including chlorantraniliprole. Previous studies have reported several protein-coding genes that involved in chlorantraniliprole resistance, but research on resistance mechanisms at the post-transcription level is still limited. In this study, a global screen of microRNAs (miRNAs) associated with chlorantraniliprole resistance in P. xylostella was performed. The small RNA libraries for a susceptible (CHS) and two chlorantraniliprole resistant strains (CHR, ZZ) were constructed and sequenced, and a total of 199 known and 30 novel miRNAs were identified. Among them, 23 miRNAs were differentially expressed between CHR and CHS, and 90 miRNAs were differentially expressed between ZZ and CHS, of which 11 differentially expressed miRNAs were identified in both CHR and ZZ. Using miRanda and RNAhybrid, a total of 1,411 target mRNAs from 102 differentially expressed miRNAs were predicted, including mRNAs in several groups of detoxification enzymes. The expression of several differentially expressed miRNAs and their potential targets was validated by qRT-PCR. The results may provide important clues for further study of the mechanisms of miRNA-mediated chlorantraniliprole resistance in DBM and other target insects.
Lithium Accumulates in Neurogenic Brain Regions as Revealed by High Resolution Ion Imaging
Authors: Zanni Giulia , Michno Wojciech , Di Martino Elena , Tjärnlund-Wolf Anna , Pettersson Jean , Mason Charlotte Elizabeth , Hellspong Gustaf , Blomgren Klas , Hanrieder Jörg 
Published: January 2017

AbstractLithium (Li) is a potent mood stabilizer and displays neuroprotective and neurogenic properties. Despite extensive investigations, the mechanisms of action have not been fully elucidated, especially in the juvenile, developing brain. Here we characterized lithium distribution in the juvenile mouse brain during 28 days of continuous treatment that result in clinically relevant serum concentrations. By using Time-of-Flight Secondary Ion Mass Spectrometry- (ToF-SIMS) based imaging we were able to delineate temporospatial lithium profile throughout the brain and concurrent distribution of endogenous lipids with high chemical specificity and spatial resolution. We found that Li accumulated in neurogenic regions and investigated the effects on hippocampal neurogenesis. Lithium increased proliferation, as judged by Ki67-immunoreactivity, but did not alter the number of doublecortin-positive neuroblasts at the end of the treatment period. Moreover, ToF-SIMS revealed a steady depletion of sphingomyelin in white matter regions during 28d Li-treatment, particularly in the olfactory bulb. In contrast, cortical levels of cholesterol and choline increased over time in Li-treated mice. This is the first study describing ToF-SIMS imaging for probing the brain-wide accumulation of supplemented Li in situ. The findings demonstrate that this technique is a powerful approach for investigating the distribution and effects of neuroprotective agents in the brain.
Novel G9 rotavirus strains co-circulate in children and pigs, Taiwan
Authors: Wu Fang-Tzy , Bányai Krisztián , Jiang Baoming , Liu Luke Tzu-Chi , Marton Szilvia , Huang Yhu-Chering , Huang Li-Min , Liao Ming-Hui , Hsiung Chao A. 
Published: January 2017

AbstractMolecular epidemiologic studies collecting information of the spatiotemporal distribution of rotavirus VP7 (G) and VP4 (P) genotypes have shown evidence for the increasing global importance of genotype G9 rotaviruses in humans and pigs. Sequence comparison of the VP7 gene of G9 strains identified different lineages to prevail in the respective host species although some of these lineages appear to be shared among heterologous hosts providing evidence of interspecies transmission events. The majority of these events indicates the pig-to-human spillover, although a reverse route of transmission cannot be excluded either. In this study, new variants of G9 rotaviruses were identified in two children with diarrhea and numerous pigs in Taiwan. Whole genome sequence and phylogenetic analyses of selected strains showed close genetic relationship among porcine and human strains suggesting zoonotic origin of Taiwanese human G9 strains detected in 2014–2015. Although the identified human G9P[19] and G9P[13] rotaviruses represented minority strains, the repeated detection of porcine-like rotavirus strains in Taiwanese children over time justifies the continuation of synchronized strain surveillance in humans and domestic animals.
A comprehensive platform for the analysis of ubiquitin-like protein modifications using in vivo biotinylation
Authors: Pirone Lucia , Xolalpa Wendy , Sigurðsson Jón Otti , Ramirez Juanma , Pérez Coralia , González Monika , de Sabando Ainara Ruiz , Elortza Félix , Rodriguez Manuel S. , Mayor Ugo , Olsen Jesper V. , Barrio Rosa , Sutherland James D. 
Published: January 2017

AbstractPost-translational modification by ubiquitin and ubiquitin-like proteins (UbLs) is fundamental for maintaining protein homeostasis. Efficient isolation of UbL conjugates is hampered by multiple factors, including cost and specificity of reagents, removal of UbLs by proteases, distinguishing UbL conjugates from interactors, and low quantities of modified substrates. Here we describe bioUbLs, a comprehensive set of tools for studying modifications in Drosophila and mammals, based on multicistronic expression and in vivo biotinylation using the E. coli biotin protein ligase BirA. While the bioUbLs allow rapid validation of UbL conjugation for exogenous or endogenous proteins, the single vector approach can facilitate biotinylation of most proteins of interest. Purification under denaturing conditions inactivates deconjugating enzymes and stringent washes remove UbL interactors and non-specific background. We demonstrate the utility of the method in Drosophila cells and transgenic flies, identifying an extensive set of putative SUMOylated proteins in both cases. For mammalian cells, we show conjugation and localization for many different UbLs, with the identification of novel potential substrates for UFM1. Ease of use and the flexibility to modify existing vectors will make the bioUbL system a powerful complement to existing strategies for studying this important mode of protein regulation.
Epigenetic modifications at DMRs of placental genes are subjected to variations in normal gestation, pathological conditions and folate supplementation
Authors: Rahat Beenish , Mahajan Aatish , Bagga Rashmi , Hamid Abid , Kaur Jyotdeep 
Published: January 2017

AbstractInvasive placentation and cancer development shares many similar molecular and epigenetic pathways. Paternally expressed, growth promoting genes (SNRPN, PEG10 and MEST) which are known to play crucial role in tumorogenesis, are not well studied during placentation. This study reports for the first time of the impact of gestational-age, pathological conditions and folic acid supplementation on dynamic nature of DNA and histone methylation present at their differentially methylated regions (DMRs). Here, we reported the association between low DNA methylation/H3K27me3 and higher expression of SNRPN, PEG10 and MEST in highly proliferating normal early gestational placenta. Molar and preeclamptic placental villi, exhibited aberrant changes in methylation levels at DMRs of these genes, leading to higher and lower expression of these genes, respectively, in reference to their respective control groups. Moreover, folate supplementation could induce gene specific changes in mRNA expression in placental cell lines. Further, MEST and SNRPN DMRs were observed to show the potential to act as novel fetal DNA markers in maternal plasma. Thus, variation in methylation levels at these DMRs regulate normal placentation and placental disorders. Additionally, the methylation at these DMRs might also be susceptible to folic acid supplementation and has the potential to be utilized in clinical diagnosis.
Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling
Authors: Urlep Žiga , Lorbek Gregor , Perše Martina , Jeruc Jera , Juvan Peter , Matz-Soja Madlen , Gebhardt Rolf , Björkhem Ingemar , Hall Jason A. , Bonneau Richard , Littman Dan R. , Rozman Damjana 
Published: January 2017

AbstractDevelopment of mice with hepatocyte knockout of lanosterol 14α-demethylase (HCyp51−/−) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12. RORC transcriptional activity is diminished in livers of all runt mice, in correlation with the depletion of potential RORC ligands subsequent to CYP51 disruption. Further evidence for this comes from the global analysis that identified a crucial overlap between hepatic Cyp51−/− and Rorc−/− expression profiles. Additionally, the reduction in RORA and RORC transcriptional activity was greater in adult HCyp51−/− females than males, which correlates well with their downregulated amino and fatty acid metabolism. Overall, we identify a global and sex-dependent transcriptional de-regulation due to the block in cholesterol synthesis during development of the Cyp51 knockout mice and provide in vivo evidence that sterol intermediates downstream of lanosterol may regulate the hepatic RORC activity.
Tailoring femtosecond 1.5-μm Bessel beams for manufacturing high-aspect-ratio through-silicon vias
Authors: He Fei , Yu Junjie , Tan Yuanxin , Chu Wei , Zhou Changhe , Cheng Ya , Sugioka Koji 
Published: January 2017

AbstractThree-dimensional integrated circuits (3D ICs) are an attractive replacement for conventional 2D ICs as high-performance, low-power-consumption, and small-footprint microelectronic devices. However, one of the major remaining challenges is the manufacture of high-aspect-ratio through-silicon vias (TSVs), which is a crucial technology for the assembly of 3D Si ICs. Here, we present the fabrication of high-quality TSVs using a femtosecond (fs) 1.5-μm Bessel beam. To eliminate the severe ablation caused by the sidelobes of a conventional Bessel beam, a fs Bessel beam is tailored using a specially designed binary phase plate. We demonstrate that the tailored fs Bessel beam can be used to fabricate a 2D array of approximately ∅10-μm TSVs on a 100-μm-thick Si substrate without any sidelobe damage, suggesting potential application in the 3D assembly of 3D Si ICs.