bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning How to Manage the Boundaries Between Life Domains
Authors: Rexroth Miriam , Feldmann Elisa , Peters Anna , Sonntag Karlheinz
Published: July 2016

Abstract. To evaluate the effects of a boundary management intervention on boundary management, recovery experiences, and well-being variables, we conducted a quasi-experimental study using an intervention lasting two consecutive days. The sample consisted of 64 employees of a large international German company; 37 in the experimental group and 27 in the control group. Boundary management, recovery experiences, and well-being outcomes were measured before the intervention and 2 weeks after the intervention. Analyses of covariance revealed an increase in boundary creation and detachment, but, contrary to the hypothesis, a decrease in control during leisure time after the intervention. No effects were found for the well-being variables.
Gütekriterien einer deutschen Kurzform des Communicator Style Measure (CSM-D)
Authors: Cohrs Carina , Diebig Mathias , Rowold Jens , Bormann Kai C.
Published: July 2016

Zusammenfassung. Ziel der vorliegenden Validierungsstudie ist die Adaption einer Selbst- und Fremdbildversion des amerikanischen Communicator Style Measure (CSM) von Robert Norton (1983) in den deutschen Sprachraum. Norton (1983) postuliert elf verschiedene Kommunikationsstile, die mit Hilfe des CSM mit 51 Items valide erfasst werden können. Die Ergebnisse der konfirmatorischen Faktorenanalysen zeigen, dass die Daten die elffaktorielle Struktur des CSM sowohl in der Selbst- als auch in der Fremdbildversion des CSM gut abbilden. Zudem konnte der CSM durch die Reduktion der Itemanzahl auf 32 Items insgesamt deutlich ökonomischer gestaltet werden. Hinsichtlich der diskriminanten und konvergenten Validität konnte die Mehrzahl der postulierten Hypothesen bestätigt und damit insgesamt die Validität der Skalen gestützt werden. Zudem konnten signifikante Einflüsse verschiedener Kommunikationsstile auf subjektive organisationale Leistungskriterien nachgewiesen werden.
Climate Warming May Have Helped Kill the Dinosaurs
Authors: Coombs Amy
Published: July 2016

New evidence indicates ancient warming spells that coincided with prodigious volcanism and a powerful meteorite impact, both seen as possible causes of mass extinctions about 66 million years ago.
Intracellular glutathione determines bortezomib cytotoxicity in multiple myeloma cells
Authors: Starheim K K , Holien T , Misund K , Johansson I , Baranowska K A , Sponaas A-M , Hella H , Buene G , Waage A , Sundan A , Bjørkøy G
Published: July 2016

Multiple myeloma (myeloma in short) is an incurable cancer of antibody-producing plasma cells that comprise 13% of all hematological malignancies. The proteasome inhibitor bortezomib has improved treatment significantly, but inherent and acquired resistance to the drug remains a problem. We here show that bortezomib-induced cytotoxicity was completely dampened when cells were supplemented with cysteine or its derivative, glutathione (GSH) in ANBL-6 and INA-6 myeloma cell lines. GSH is a major component of the antioxidative defense in eukaryotic cells. Increasing intracellular GSH levels fully abolished bortezomib-induced cytotoxicity and transcriptional changes. Elevated intracellular GSH levels blocked bortezomib-induced nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2)-associated stress responses, including upregulation of the xCT subunit of the Xc- cystine-glutamate antiporter. INA-6 cells conditioned to increasing bortezomib doses displayed reduced bortezomib sensitivity and elevated xCT levels. Inhibiting Xc- activity potentiated bortezomib-induced cytotoxicity in myeloma cell lines and primary cells, and re-established sensitivity to bortezomib in bortezomib-conditioned cells. We propose that intracellular GSH level is the main determinant of bortezomib-induced cytotoxicity in a subset of myeloma cells, and that combined targeting of the proteasome and the Xc- cystine-glutamate antiporter can circumvent bortezomib resistance.
Association mapping reveals novel serpentine adaptation gene clusters in a population of symbiotic Mesorhizobium
Authors: Porter Stephanie S , Chang Peter L , Conow Christopher A , Dunham Joseph P , Friesen Maren L
Published: July 2016

The genetic variants that underlie microbial environmental adaptation are key components of models of microbial diversification. Characterizing adaptive variants and the pangenomic context in which they evolve remains a frontier in understanding how microbial diversity is generated. The genomics of rhizobium adaptation to contrasting soil environments is ecologically and agriculturally important because these bacteria are responsible for half of all current biologically fixed nitrogen, yet they live the majority of their lives in soil. Our study uses whole-genome sequencing to describe the pan-genome of a focal clade of wild mesorhizobia that show contrasting levels of nickel adaptation despite high relatedness (99.8% identity at 16S). We observe ecotypic specialization within an otherwise genomically cohesive population, rather than finding distinct specialized bacterial lineages in contrasting soil types. This finding supports recent reports that heterogeneous environments impose selection that maintains differentiation only at a small fraction of the genome. Our work further uses a genome-wide association study to propose candidate genes for nickel adaptation. Several candidates show homology to genetic systems involved in nickel tolerance and one cluster of candidates correlates perfectly with soil origin, which validates our approach of ascribing genomic variation to adaptive divergence.
The ER membrane-anchored ubiquitin ligase Hrd1 is a positive regulator of T-cell immunity
Authors: Xu Yuanming , Zhao Fang , Qiu Quan , Chen Kun , Wei Juncheng , Kong Qingfei , Gao Beixue , Melo-Cardenas Johanna , Zhang Bin , Zhang Jinping , Song Jianxun , Zhang Donna D. , Zhang Jianing , Fan Yunping , Li Huabin , Fang Deyu
Published: July 2016

Identification of positive regulators of T-cell immunity induced during autoimmune diseases is critical for developing novel therapies. The endoplasmic reticulum resident ubiquitin ligase Hrd1 has recently emerged as a critical regulator of dendritic cell antigen presentation, but its role in T-cell immunity is unknown. Here we show that genetic deletion of Hrd1 in mice inhibits T-cell proliferation, production of IL-2, and differentiation of Th1 and Th17 cells, and consequently protects mice from experimental autoimmune encephalomyelitis. Hrd1 facilitates T-cell proliferation by the destruction of cyclin-dependent kinase inhibitor p27kip1, and deletion of p27kip1 in Hrd1-null T-cells rescues proliferative capacity but not the production of cytokines, including IL-2, IFN-γ and IL-17. T-cell expression of Hrd1 is higher in patients with multiple sclerosis than in healthy individuals, and knockdown of Hrd1 in human CD4+ T cells inhibits activation and differentiation to Th1 and Th17 cells. Our study identifies Hrd1 as a previously unappreciated positive regulator of T cells and implies that Hrd1 is a potential therapeutic target for autoimmune diseases.
Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia
Authors: Sun Kaiqi , Zhang Yujin , D’Alessandro Angelo , Nemkov Travis , Song Anren , Wu Hongyu , Liu Hong , Adebiyi Morayo , Huang Aji , Wen Yuan E. , Bogdanov Mikhail V. , Vila Alejandro , O’Brien John , Kellems Rodney E. , Dowhan William , Subudhi Andrew W. , Jameson-Van Houten Sonja , Julian Colleen G. , Lovering Andrew T. , Safo Martin , Hansen Kirk C. , Roach Robert C. , Xia Yang
Published: July 2016

Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity. Mouse genetic studies show that elevated erythrocyte Sphk1-induced S1P protects against tissue hypoxia by inducing O2release. Mechanistically, we show that intracellular S1P promotes deoxygenated Hb anchoring to the membrane, enhances the release of membrane-bound glycolytic enzymes to the cytosol, induces glycolysis and thus the production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific glycolytic intermediate, which facilitates O2release. Altogether, we reveal S1P as an intracellular hypoxia-responsive biolipid promoting erythrocyte glycolysis, O2delivery and thus new therapeutic opportunities to counteract tissue hypoxia.
Structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity
Authors: Stavrinides Anna , Tatsis Evangelos C. , Caputi Lorenzo , Foureau Emilien , Stevenson Clare E. M. , Lawson David M. , Courdavault Vincent , O'Connor Sarah E.
Published: July 2016

Plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. These changes in stereochemistry dramatically impact biological activity. Notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. We reported a medium chain dehydrogenase/reductase (MDR) from Catharanthus roseus that catalyses formation of a heteroyohimbine isomer. Here we report the discovery of additional heteroyohimbine synthases (HYSs), one of which produces a mixture of diastereomers. The crystal structures for three HYSs have been solved, providing insight into the mechanism of reactivity and stereoselectivity, with mutation of one loop transforming product specificity. Localization and gene silencing experiments provide a basis for understanding the function of these enzymes in vivo. This work sets the stage to explore how MDRs evolved to generate structural and biological diversity in specialized plant metabolism and opens the possibility for metabolic engineering of new compounds based on this scaffold.
RNA polymerase I–Rrn3 complex at 4.8 Å resolution
Authors: Engel Christoph , Plitzko Jürgen , Cramer Patrick
Published: July 2016

Transcription of ribosomal DNA by RNA polymerase I (Pol I) requires the initiation factor Rrn3. Here we report the cryo-EM structure of the Pol I–Rrn3 complex at 4.8 Å resolution. The structure reveals how Rrn3 binding converts an inactive Pol I dimer into an initiation-competent monomeric complex and provides insights into the mechanisms of Pol I-specific initiation and regulation.
Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization
Authors: Kato Kazuki , Satouh Yuhkoh , Nishimasu Hiroshi , Kurabayashi Arisa , Morita Junko , Fujihara Yoshitaka , Oji Asami , Ishitani Ryuichiro , Ikawa Masahito , Nureki Osamu
Published: July 2016

Sperm–egg fusion is the critical step in mammalian fertilization, and requires the interaction between IZUMO1 on the sperm surface and JUNO (also known as folate receptor (FR) 4 or IZUMO1R) on the egg surface. Whereas other FRs bind and uptake folates, JUNO binds IZUMO1 and establishes the cell–cell adhesion. However, the mechanism of IZUMO1 recognition by JUNO has remained elusive. Here we report the crystal structure of mouse JUNO, at 2.3 Å resolution. A structural comparison of JUNO with the FRs revealed that JUNO and the FRs have similar overall structures, but JUNO lacks the folate-binding pocket, thereby explaining the inability of JUNO to bind folate. Further complementation of Juno knockout eggs with mutant Juno messenger RNAs revealed that the conserved, surface-exposed tryptophan residue of JUNO is required for sperm binding and fertilization. Our structure-based in vivo functional analyses provide a framework towards a mechanistic understanding of mammalian gamete recognition.
Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV
Authors: Akil Abdellah , Peng Juan , Omrane Mohyeddine , Gondeau Claire , Desterke Christophe , Marin Mickaël , Tronchère Hélène , Taveneau Cyntia , Sar Sokhavuth , Briolotti Philippe , Benjelloun Soumaya , Benjouad Abdelaziz , Maurel Patrick , Thiers Valérie , Bressanelli Stéphane , Samuel Didier , Bréchot Christian , Gassama-Diagne Ama
Published: July 2016

The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway.
The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions
Authors: Dorland Yvonne L. , Malinova Tsveta S. , van Stalborch Anne-Marieke D. , Grieve Adam G. , van Geemen Daphne , Jansen Nicolette S. , de Kreuk Bart-Jan , Nawaz Kalim , Kole Jeroen , Geerts Dirk , Musters René J. P. , de Rooij Johan , Hordijk Peter L. , Huveneers Stephan
Published: July 2016

Vascular homoeostasis, development and disease critically depend on the regulation of endothelial cell–cell junctions. Here we uncover a new role for the F-BAR protein pacsin2 in the control of VE-cadherin-based endothelial adhesion. Pacsin2 concentrates at focal adherens junctions (FAJs) that are experiencing unbalanced actomyosin-based pulling. FAJs move in response to differences in local cytoskeletal geometry and pacsin2 is recruited consistently to the trailing end of fast-moving FAJs via a mechanism that requires an intact F-BAR domain. Photoconversion, photobleaching, immunofluorescence and super-resolution microscopy reveal polarized dynamics, and organization of junctional proteins between the front of FAJs and their trailing ends. Interestingly, pacsin2 recruitment inhibits internalization of the VE-cadherin complex from FAJ trailing ends and is important for endothelial monolayer integrity. Together, these findings reveal a novel junction protective mechanism during polarized trafficking of VE-cadherin, which supports barrier maintenance within dynamic endothelial tissue.
Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors
Authors: Hsieh Tung-Ju , Lin Hsien-Ya , Tu Zhijay , Lin Ting-Chien , Wu Shang-Chuen , Tseng Yu-Yao , Liu Fu-Tong , Hsu Shang-Te Danny , Lin Chun-Hung
Published: July 2016

Human galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3’-deoxy-3,3’-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside, recently approved for the treatment of idiopathic pulmonary fibrosis) and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A–E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from μM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins.
Genetic Variants in the Transcriptional Regulatory Region of the ALOX5AP gene and Susceptibility to Ischemic Stroke in Chinese Populations
Authors: Yang Dongzhi , Huang Xiangnan , Cui Chuanju , Zhang Yuchao , Li Ya , Zang Xin , He Ying , Zheng Hong
Published: July 2016

No coding sequence variants of the ALOX5AP gene that lead to amino acid substitutions have been identified. A two-stage study design was used to explore the relationship between variants in the transcriptional regulatory region of ALOX5AP gene and ischemic stroke (IS) risk in Chinese populations. IS was determined using CT and/or MRI. First, 18 SNPs, located in the upstream promoter region of ALOX5AP gene, were genotyped in 200 IS patients and 200 controls. And one potential associated SNP (rs17222919) was identified (P = 0.005,OR = 0.623, 95% CI: 0.448~0.866). Next, another independent case-control cohort comprising 810 IS patients and 825 matched controls was recruited to investigate the role of rs17222919, rs9579646 polymorphisms and their haplotypes in IS risk. The G allele frequency of rs17222919 in the IS group was significantly lower than that in control group (P = 0.007, OR = 0.792, 95% CI: 0.669~0.937). T-A and G-A haplotypes were associated with IS (P = 0.001,OR = 1.282, 95% CI:1.100~1.495; P = 0.0001, OR = 0.712, 95% CI: 0.598~0.848; respectively). Our study providesevidence that rs17222919 is a potential genetic protective factor against IS. Furthermore, the T-A haplotype is a risk factor and the G-A haplotype is a protective factor against IS in Chinese population.
Reflection type metasurface designed for high efficiency vectorial field generation
Authors: Wang Shiyi , Zhan Qiwen
Published: July 2016

We propose a reflection type metal-insulator-metal (MIM) metasurface composed of hybrid nano-antennas for comprehensive spatial engineering of the properties of optical fields. The capability of such structure is illustrated in the design of a device that can be used to produce a radially polarized vectorial beam for optical needle field generation. This device consists of uniformly segmented sectors of high efficiency MIM metasurface. With each of the segment sector functioning as a local quarter-wave-plate (QWP), the device is designed to convert circularly polarized incidence into local linear polarization to create an overall radial polarization with corresponding binary phases and extremely high dynamic range amplitude modulation. The capability of such devices enables the generation of nearly arbitrarily complex optical fields that may find broad applications that transcend disciplinary boundaries.
Knock out of the PHOSPHATE 2 Gene TaPHO2-A1 Improves Phosphorus Uptake and Grain Yield under Low Phosphorus Conditions in Common Wheat
Authors: Ouyang Xiang , Hong Xia , Zhao Xueqiang , Zhang Wei , He Xue , Ma Wenying , Teng Wan , Tong Yiping
Published: July 2016

MiR399 and its targetPHOSPHATE2 (PHO2) play pivotal roles in phosphate signaling in plants. Loss of function mutation inPHO2leads to excessive Pi accumulation in shoots and growth retardation in diploid plants likeArabidopsis thalianaand rice (Oryza sativa). Here we isolated threePHO2homologous genesTaPHO2-A1, -B1and -D1from hexaploid wheat (Triticum aestivum). TheseTaPHO2genes all contained miR399-binding sites and were able to be degraded by tae-miR399.TaPHO2-D1was expressed much more abundantly thanTaPHO2-A1and -B1. The ion beam-induced deletion mutants were used to analyze the effects ofTaPHO2son phosphorus uptake and plant growth. Thetapho2-a1, tapho2-b1andtapho2-d1mutants all had significant higher leaf Pi concentrations than did the wild type, withtapho2-d1having the strongest effect andtapho2-b1the weakest. Two consecutive field experiments showed that knocking outTaPHO2-D1reduced plant height and grain yield under both low and high phosphorus conditions. However, knocking outTaPHO2-A1significantly increased phosphorus uptake and grain yield under low phosphorus conditions, with no adverse effect on grain yield under high phosphorus conditions. Our results indicated thatTaPHO2sinvolved in phosphorus uptake and translocation and molecular engineeringTaPHO2shows potential in improving wheat yield with less phosphorus fertilizer.
Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1
Authors: El-Naga Reem N. , Mahran Yasmen F.
Published: July 2016

Nephrotoxicity associated with the clinical use of the anticancer drug cisplatin is a limiting problem. Thus, searching for new protective measures is required. Indole-3-carbinol is a powerful anti-oxidant, anti-inflammatory and anti-tumor agent. The present study aimed to investigate the potential protective effect of indole-3-carbinol against cisplatin-induced acute nephrotoxicity in rats. Rats were pre-treated with 20 mg/kg indole-3-carbinol orally before giving cisplatin (7 mg/kg). Cisplatin-induced acute nephrotoxicity was demonstrated where relative kidney weight, BUN and serum creatinine were significantly increased. Increased oxidative stress was evident in cisplatin group where GSH and SOD tissue levels were significantly depleted. Also, lipid peroxidation and NOX-1 were increased as compared to the control. Additionally, renal expression of pro-inflammatory mediators was induced by cisplatin. Cisplatin-induced cell death was shown by increased caspase-3 and decreased expression of EGF, IGF-1 and IGF-1 receptor. Nephrotoxicity, oxidative stress, inflammation and apoptotic effects induced by cisplatin were significantly ameliorated by indole-3-carbinol pre-treatment. Besides, the role of CGRP in cisplatin-induced nephrotoxicity was explored. Furthermore, cisplatin cytotoxic activity was significantly enhanced by indole-3-carbinol pre-treatment in vitro. In conclusion, indole-3-carbinol provides protection against cisplatin-induced nephrotoxicity. Also, reduced expression of CGRP may play a role in the pathogenesis of cisplatin-induced renal injury.
Weight Gain in Infancy and Overweight or Obesity in Childhood across the Gestational Spectrum: a Prospective Birth Cohort Study
Authors: Wang Guoying , Johnson Sara , Gong Yiwei , Polk Sarah , Divall Sara , Radovick Sally , Moon Margaret , Paige David , Hong Xiumei , Caruso Deanna , Chen Zhu , Mallow Eric , Walker Sheila O. , Mao Guangyun , Pearson Colleen , Wang Mei-Cheng , Zuckerman Barry , Cheng Tina L. , Wang Xiaobin
Published: July 2016

This study aimed to investigate the optimal degree of weight gain across the gestational spectrum in 1971 children enrolled at birth and followed up to age 7 years. Weight gain in infancy was categorized into four groups based on weight gain z-scores: slow (<−0.67), on track (−0.67 to 0.67), rapid (0.67 to 1.28), and extremely rapid (>1.28). Underweight and overweight or obesity (OWO) were defined as a body mass index ≤5th and ≥85th percentile, respectively, for age and gender. In our population, OWO was far more common than underweight (39.7% vs. 3.6%). Weight gain tracked strongly from age 4 to 24 months, and was positively associated with OWO and an unfavorable pattern of metabolic biomarkers, although the degree of weight gain for the risk was different across gestational categories. Extremely rapid weight gain led to a particularly high risk of OWO among children born early term and late preterm: odds ratio: 3.3 (95% confidence interval: 1.9 to 5.5) and 3.7 (1.8 to 7.5), respectively, as compared to those with on track weight gain. Our findings suggest that monitoring and ensuring optimal weight gain across the entire gestational spectrum beginning from birth represents a first step towards primary prevention of childhood obesity.
Copy number variation of E3 ubiquitin ligase genes in peripheral blood leukocyte and colorectal cancer
Authors: Bi Haoran , Tian Tian , Zhu Lin , Zhou Haibo , Hu Hanqing , Liu Yanhong , Li Xia , Hu Fulan , Zhao Yashuang , Wang Guiyu
Published: July 2016

Given that E3 ubiquitin ligases (E3) regulate specific protein degradation in many cancer-related biological processes. E3 copy number variation (CNV) may affect the development and prognosis of colorectal cancer (CRC). Therefore, we detected CNVs of five E3 genes in 518 CRC patients and 518 age, gender and residence matched controls in China and estimated the association between E3 gene CNVs and CRC risk and prognosis. We also estimated their interactions with environmental factors and CRC risk. We find a significant association between the CNVs of MDM2 and CRC risk (amp v.s. wt: odds ratio = 14.37, 95% confidence interval: 1.27, 163.74, P = 0.032), while SKP2 CNVs may significantly decrease CRC risk (del v.s. wt: odds ratio = 0.32, 95% confidence interval: 0.10, 1.00, P = 0.050). However, we find no significant association between the CNVs of other genes and CRC risk. The only significant gene-environment interaction effects are between SKP2 CNVs and consumption of fish and/or fruit (P = 0.014 and P = 0.035) and between FBXW7 CNVs and pork intake (P = 0.040). Finally, we find marginally significant association between β-TRCP CNVs and CRC prognosis (amp v.s. wt, hazard ratio = 0.42, 95% confidence interval: 0.19, 0.97, P = 0.050).
Hollow cathode lamp based Faraday anomalous dispersion optical filter
Authors: Pan Duo , Xue Xiaobo , Shang Haosen , Luo Bin , Chen Jingbiao , Guo Hong
Published: July 2016

The Faraday anomalous dispersion optical filter (FADOF), which has acquired wide applications, is mainly limited to some gaseous elements and low melting-point metals before, for the restriction of the attainable atomic density. In conventional FADOF systems a high atomic density is usually achieved by thermal equilibrium at the saturated vapor pressure, hence for elements with high melting-points a high temperature is required. To avoid this restriction, we propose a scheme of FADOF based on the hollow cathode lamp (HCL), instead of atomic vapor cells. Experimental results in strontium atoms verified this scheme, where a transmission peak corresponding to the 88Sr (5s2)1S0 − (5s5p)1P1 transition (461 nm) is obtained, with a maximum transmittance of 62.5% and a bandwith of 1.19 GHz. The dependence of transmission on magnetic field and HCL discharge current is also studied. Since the state-of-art commercial HCLs cover about 70 elements, this scheme can greatly expand the applications of FADOFs and the abundant atomic transitions they provide bring the HCL based FADOFs potential applications for frequency stabilization.
Metabonomics applied in exploring the antitumour mechanism of physapubenolide on hepatocellular carcinoma cells by targeting glycolysis through the Akt-p53 pathway
Authors: Ma Ting , Fan Bo-Yi , Zhang Chao , Zhao Hui-Jun , Han Chao , Gao Cai-Yun , Luo Jian-Guang , Kong Ling-Yi
Published: July 2016

Metabolomics can be used to identify potential markers and discover new targets for future therapeutic interventions. Here, we developed a novel application of the metabonomics method based on gas chromatography-mass spectrometry (GC/MS) analysis and principal component analysis (PCA) for rapidly exploring the anticancer mechanism of physapubenolide (PB), a cytotoxic withanolide isolated from Physalis species. PB inhibited the proliferation of hepatocellular carcinoma cells in vitro and in vivo, accompanied by apoptosis-related biochemical events, including the cleavage of caspase-3/7/9 and PARP. Metabolic profiling analysis revealed that PB disturbed the metabolic pattern and significantly decreased lactate production. This suggests that the suppression of glycolysis plays an important role in the anti-tumour effects induced by PB, which is further supported by the decreased expression of glycolysis-related genes and proteins. Furthermore, the increased level of p53 and decreased expression of p-Akt were observed and the attenuated glycolysis and enhanced apoptosis were reversed in the presence of Akt cDNA or p53 siRNA. These results confirm that PB exhibits anti-cancer activities through the Akt-p53 pathway. Our study not only reports for the first time the anti-tumour mechanism of PB, but also suggests that PB is a promising therapeutic agent for use in cancer treatments and that metabolomic approaches provide a new strategy to effectively explore the molecular mechanisms of promising anticancer compounds.
Mitochondrial cereblon functions as a Lon-type protease
Authors: Kataoka Kosuke , Nakamura China , Asahi Toru , Sawamura Naoya
Published: July 2016

Lon protease plays a major role in the protein quality control system in mammalian cell mitochondria. It is present in the mitochondrial matrix and degrades oxidized and misfolded proteins, thereby protecting the cell from various extracellular stresses, including oxidative stress. The intellectual disability-associated and thalidomide-binding protein cereblon (CRBN) contains a large, highly conserved Lon domain. However, whether CRBN has Lon protease-like function remains unknown. Here, we determined if CRBN has a protective function against oxidative stress, similar to Lon protease. We report that CRBN partially distributes in mitochondria, suggesting it has a mitochondrial function. To specify the mitochondrial role of CRBN, we mitochondrially expressed CRBN in human neuroblastoma SH-SY5Y cells. The resulting stable SH-SY5Y cell line showed no apparent effect on the mitochondrial functions of fusion, fission and membrane potential. However, mitochondrially expressed CRBN exhibited protease activity and was induced by oxidative stress. In addition, stably expressed cells exhibited suppressed neuronal cell death induced by hydrogen peroxide. These results suggest that CRBN functions specifically as a Lon-type protease in mitochondria.
Four-state memory based on a giant and non-volatile converse magnetoelectric effect in FeAl/PIN-PMN-PT structure
Authors: Wei Yanping , Gao Cunxu , Chen Zhendong , Xi Shibo , Shao Weixia , Zhang Peng , Chen Guilin , Li Jiangong
Published: July 2016

We report a stable, tunable and non-volatile converse magnetoelectric effect (ME) in a new type of FeAl/PIN-PMN-PT heterostructure at room temperature, with a giant electrical modulation of magnetization for which the maximum relative magnetization change (ΔM/M) is up to 66%. The 109° ferroelastic domain switching in the PIN-PMN-PT and coupling with the ferromagnetic (FM) film via uniaxial anisotropy originating from the PIN-PMN-PT (011) surface are the key roles in converse ME effect. We also propose here a new, four-state memory through which it is possible to modify the remanent magnetism state by adjusting the electric field. This work represents a helpful approach to securing electric-writing magnetic-reading with low energy consumption for future high-density information storage applications.
Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models
Authors: Ameku Tomonaga , Taura Daisuke , Sone Masakatsu , Numata Tomohiro , Nakamura Masahiro , Shiota Fumihiko , Toyoda Taro , Matsui Satoshi , Araoka Toshikazu , Yasuno Tetsuhiko , Mae Shin-Ichi , Kobayashi Hatasu , Kondo Naoya , Kitaoka Fumiyo , Amano Naoki , Arai Sayaka , Ichisaka Tomoko , Matsuura Norio , Inoue Sumiko , Yamamoto Takuya , Takahashi Kazutoshi , Asaka Isao , Yamada Yasuhiro , Ubara Yoshifumi , Muso Eri , Fukatsu Atsushi , Watanabe Akira , Sato Yasunori , Nakahata Tatsutoshi , Mori Yasuo , Koizumi Akio , Nakao Kazuwa , Yamanaka Shinya , Osafune Kenji
Published: July 2016

Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs. The vascular cells differentiated from ADPKD-iPSCs showed altered Ca2+ entry and gene expression profiles compared with those of iPSCs from non-ADPKD subjects. We found that the expression level of a metalloenzyme gene, matrix metalloproteinase (MMP) 1, was specifically elevated in iPSC-derived endothelia from ADPKD patients with ICAs. Furthermore, we confirmed the correlation between the serum MMP1 levels and the development of ICAs in 354 ADPKD patients, indicating that high serum MMP1 levels may be a novel risk factor. These results suggest that cellular disease models with ADPKD-specific iPSCs can be used to study the disease mechanisms and to identify novel disease-related molecules or risk factors.
Improved quality of life in patients with no-option critical limb ischemia undergoing gene therapy with DVC1-0101
Authors: Matsumoto Takuya , Tanaka Michiko , Yoshiya Keiji , Yoshiga Ryosuke , Matsubara Yutaka , Horiuchi-Yoshida Kumi , Yonemitsu Yoshikazu , Maehara Yoshihiko
Published: July 2016

Critical limb ischemia (CLI) has a poor prognosis and adversely affects patients’ quality of life (QOL). Therapeutic angiogenesis may improve mobility, mortality and QOL in CLI patients. However, the effectiveness of gene therapy on such patients’ QOL is unknown. DVC1-0101, a non-transmissible recombinant Sendai virus vector expressing human fibroblast growth factor-2 gene, demonstrated safety and efficacy in a phase I/II study of CLI patients. We investigated the effects of DVC1-0101 on QOL in this cohort. QOL was assessed using the Short Form-36 health survey version 2 (SF-36) in 12 patients at pre-administration, 28 days and 3, 6 and 12 months post-treatment. We examined differences between pre and post-administration QOL scores and correlations between QOL scores and vascular parameters. Patients demonstrated low baselines scores on every SF-36 dimension. Post-treatment scores showed significant improvements in physical functioning at 3 and 6 months (P < 0.05), role-physical at 3, 6 and 12 months (P < 0.05), bodily pain at 1, 3, 6 and 12 months (P < 0.05), vitality at 1, 6 and 12 months (P < 0.05) and physical component summary at 6 and 12 months (P < 0.05). DVC1-0101-based gene therapy may improve QOL in CLI patients over a 6-month period.
Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells
Authors: Song Man , Wang Yu , Shang Zeng-Fu , Liu Xiao-Dan , Xie Da-Fei , Wang Qi , Guan Hua , Zhou Ping-Kun
Published: July 2016

Radiation-induced bystander effect (RIBE) describes a set of biological effects in non-targeted cells that receive bystander signals from the irradiated cells. RIBE brings potential hazards to adjacent normal tissues in radiotherapy, and imparts a higher risk than previously thought. Excessive release of some substances from irradiated cells into extracellular microenvironment has a deleterious effect. For example, cytokines and reactive oxygen species have been confirmed to be involved in RIBE process via extracellular medium or gap junctions. However, RIBE-mediating signals and intercellular communication pathways are incompletely characterized. Here, we first identified a set of differentially expressed miRNAs in the exosomes collected from 2 Gy irradiated human bronchial epithelial BEP2D cells, from which miR-7-5p was found to induce autophagy in recipient cells. This exosome-mediated autophagy was significantly attenuated by miR-7-5p inhibitor. Moreover, our data demonstrated that autophagy induced by exosomal miR-7-5p was associated with EGFR/Akt/mTOR signaling pathway. Together, our results support the involvement of secretive exosomes in propagation of RIBE signals to bystander cells. The exosomes-containing miR-7-5p is a crucial mediator of bystander autophagy.
Correction: Photoswitchable ring-opening polymerization of lactide catalyzed by azobenzene-based thiourea
Authors: Dai Zhongran , Cui Yaqin , Chen Changjuan , Wu Jincai
Published: July 2016

Correction for ‘Photoswitchable ring-opening polymerization of lactide catalyzed by azobenzene-based thiourea’ by Zhongran Dai et al., Chem. Commun., 2016, 52, 8826–8829.
Photoactivation of the Ni-SIr state to the Ni-SIa state in [NiFe] hydrogenase: FT-IR study on the light reactivity of the ready Ni-SIr state and as-isolated enzyme revisited
Authors: Tai Hulin , Xu Liyang , Inoue Seiya , Nishikawa Koji , Higuchi Yoshiki , Hirota Shun
Published: July 2016

The Ni-SIr state of [NiFe] hydrogenase converted to its Ni-SIa state by 514.5 nm laser irradiation, whereas the Ni-SL state was light induced from a newly identified state, which was less active than any other state.
HPLC-ICP-MS for simultaneous quantification of the total and active form of the thioredoxin reductase enzyme in human serum using auranofin as an activity-based probe
Authors: Gómez-Espina Juan , Blanco-González Elisa , Montes-Bayón Maria , Sanz-Medel Alfredo
Published: July 2016

Thioredoxin reductase 1 (TrxR1) is a cytosolic and extracellular enzyme involved in cellular redox homeostasis and other important biological functions for cell survival.
Discovery and optimisation of potent and highly subtype selective Nav1.8 inhibitors with reduced cardiovascular liabilities
Authors: Bagal Sharan K. , Kemp Mark I. , Bungay Peter J. , Hay Tanya L. , Murata Yoshihisa , Payne C. Elizabeth , Stevens Edward B. , Brown Alan , Blakemore David C. , Corbett Matthew S. , Miller Duncan C. , Omoto Kiyoyuki , Warmus Joseph S.
Published: July 2016

Potent and subtype selective Nav1.8 inhibitors were designed and optimised for selectivity over hERG ion channel inhibition.
Anti-proliferative activity and DNA/BSA interactions of five mono- or di-organotin(iv) compounds derived from 2-hydroxy-N′-[(2-hydroxy-3-methoxyphenyl)methylidene]-benzohydrazone
Authors: Hong Min , Chang Guoliang , Li Rui , Niu Meiju
Published: July 2016

Five hydrazone Schiff base organotin(iv) complexes were synthesized and their anticancer mechanism was preliminarily studied.
Pt skin on Pd–Co–Zn/C ternary nanoparticles with enhanced Pt efficiency toward ORR
Authors: Xiao Weiping , Zhu Jing , Han Lili , Liu Sufen , Wang Jie , Wu Zexing , Lei Wen , Xuan Cuijuan , Xin Huolin L. , Wang Deli
Published: July 2016

Pd8CoZn@Pt/C core-shell structure nanoparticles have been successfully synthesized by using a simple impregnation-reduction and spontaneous displacement strategy, which exhibited ultra-high electrocatalytic activity and stability toward the ORR.
Synthesis of α-sulfenyl monoketones via a metal-free oxidative cross dehydrogenative coupling (CDC) reaction
Authors: Varun Begur Vasanthkumar , Gadde Karthik , Prabhu Kandikere Ramaiah
Published: July 2016

α-Sulfenyl ketones are potential precursors which find a variety of applications in organic synthesis.
Enhancing adsorptive removal of sulfate by metal layered double hydroxide functionalized Quartz-Albitophire iron ore waste: preparation, characterization and properties
Authors: Sadeghalvad B. , Azadmehr A. , Hezarkhani A.
Published: July 2016

In this study, the seemingly worthless Quartz-Albitophire iron ore mineral waste has been modified with metal double hydroxides (Mg–Al, Ni–Fe, Ni–Al and Mg–Fe) and utilized as a sulfate adsorbent which is characterized by XRD, XRF, FTIR and SEM analysis.
Self-powered graphene quantum dot/poly(vinylidene fluoride) composites with remarkably enhanced mechanical-to-electrical conversion
Authors: Lu Chong , Zhang Lei , Xu Chenwen , Yin Zhenzhong , Zhou Shaobing , Wang Jianxin , Huang Rui , Zhou Xiaoqi , Zhang Chaoliang , Yang Weiqing , Lu Jun
Published: July 2016

A self-powered piezoelectric polymer matrix composite, with remarkably enhanced mechanical-to-electrical conversion, was fabricated without any treatment of electrical poling.
Efficient aqueous hydrodeoxygenation of vanillin over a mesoporous carbon nitride-modified Pd nanocatalyst
Authors: Jiang Hezhan , Yu Xiaolong , Peng Xiaolun , Zhang Haifu , Nie Renfeng , Lu Xinhuan , Zhou Dan , Xia Qinghua
Published: July 2016

CN is prepared via polymerization between EDA and CF, which renders coordinated Pd with high activity for selective HDO of vanillin at low H2 pressure and temperature. This Pd/CN is reusable and the best TOF reaches 295.4 h−1.
Separation of xylose using a thin-film composite nanofiltration membrane: screening of interfacial polymerization factors
Authors: Mah K. H. , Yussof H. W. , Seman M. N. Abu , Mohammad A. W.
Published: July 2016

Most hydrolysis studies on biomass produce a high amount of xylose and glucose compared to other monosaccharides.
Antifouling behavior of chitosan adorned zinc oxide nanorods
Authors: Abiraman Tamilselvan , Kavitha Ganapathy , Rengasamy Ramasamy , Balasubramanian Sengottuvelan
Published: July 2016

Chitosan adorned zinc oxide nanorods (CAZO NRs) were synthesized by a chemical conversion method.
Oxidation of the titanium(0001) surface: diffusion processes of oxygen from DFT
Authors: Liu Ji , Fan Xiaofeng , Sun Changqing , Zhu Weiguang
Published: July 2016

The double-layer model of oxygen adsorption is proposed for the initial oxidation of the Ti(0001) surface based on diffusion barrier analysis.
Continuous heterogeneous hydrogenation of CO2-derived dimethyl carbonate to methanol over a Cu-based catalyst
Authors: Cui Yuanyuan , Chen Xi , Dai Wei-Lin
Published: July 2016

Copper content played a significant role in the catalytic performance of Cu/SiO2 catalysts in dimethyl carbonate hydrogenation to methanol. Optimized hydrogenation activity was achieved over the 40Cu/SiO2 sample.
Suppression of the hierarchical structure of water-assisted injection moulded iPP in the presence of a β-nucleating agent and lamellar branching of a β-crystal
Authors: Liu Xianhu , Pan Yamin , Zheng Guoqiang , Liu Chuntai
Published: July 2016

Unexpected lamellar branching of the β-crystal structure is observed in water-assisted injection molded iPP parts with a high content of β-nucleating agent.
Chondroitin sulfate-functionalized polyamidoamine-mediated miR-34a delivery for inhibiting the proliferation and migration of pancreatic cancer
Authors: Duan Yan , Xing Zhen , Yang Jiebing , Wang Yudi , Chen Jiawen , Zhang Yan , Shi Wei , Li Quanshun
Published: July 2016

Chondroitin sulfate-functionalized polyamidoamine (CS-PAMAM) was employed as a carrier in miR-34a delivery for inhibiting the cell proliferation and migration of pancreatic cancer.
Methanol aromatization over Ga-doped desilicated HZSM-5
Authors: Lai Po-Chen , Chen Chao-Huang , Hsu His-Yen , Lee Chiou-Hwang , Lin Yu-Chuan
Published: July 2016

Desilication improves mesoporosity, facilitating migration of hydrated gallium ions into cavities of desilicated Ga/HZSM-5 to form (GaO)+-Brønsted phases. The bifunctional sites promote methanol conversion to aromatics.
Structuring hybrid palladium nanoparticles in metallic monolithic reactors for continuous-flow three-phase alkyne hydrogenation
Authors: Albani Davide , Vilé Gianvito , Beltran Toro Mario Alejandro , Kaufmann Rolf , Mitchell Sharon , Pérez-Ramírez Javier
Published: July 2016

Ligand-modified palladium nanoparticles are stabilised in the microchannels of an alumina-coated metallic monolith and advantageously used in the continuous-flow three-phase semi-hydrogenation of acetylenic compounds.
Organic chemistry students' fragmented ideas about the structure and function of nucleophiles and electrophiles: a concept map analysis
Authors: Anzovino Mary E. , Bretz Stacey Lowery
Published: July 2016

Organic chemistry students struggle with multiple aspects of reaction mechanisms and the curved arrow notation used by organic chemists. Many faculty believe that an understanding of nucleophiles and electrophiles, among other concepts, is required before students can develop fluency with the electron-pushing formalism (EPF). An expert concept map was created to depict an understanding of nucleophiles and electrophiles ideally held by undergraduates. Second year organic chemistry students were interviewed and asked to give examples of nucleophiles and electrophiles and to identify them in reactions. A cognitive map was created to represent each student's understanding. The students' maps were compared to the expert map, revealing that students possess fragmented ideas about the structure and function of nucleophiles and electrophiles.
Ultrahigh affinity Raman probe for targeted live cell imaging of prostate cancer
Authors: Li Ming , Banerjee Sangeeta Ray , Zheng Chao , Pomper Martin G. , Barman Ishan
Published: July 2016

Leveraging optimally engineered SERS tags and urea-based small-molecule inhibitor of PSMA, we report an ultrahigh binding affinity imaging nanoplex for castrate resistant prostate cancer and demonstrate live single cell vibrational spectroscopic imaging at ultralow concentrations.
A protein–dye hybrid system as a narrow range tunable intracellular pH sensor
Authors: Anees Palapuravan , Sudheesh Karivachery V. , Jayamurthy Purushothaman , Chandrika Arunkumar R. , Omkumar Ramakrishnapillai V. , Ajayaghosh Ayyappanpillai
Published: July 2016

A two-component hybrid system consisting of organic dye nanoparticles (ash) and a protein (blue) at different ratios allows for the design of narrow range tunable nanoprobes for sensing and imaging of pH variations in live cells through ratiometric signalling.
Sequential and controlled release of small molecules from poly(N-isopropylacrylamide) microgel-based reservoir devices
Authors: Gao Yongfeng , Wong Ka Yee , Ahiabu Andrews , Serpe Michael J.
Published: July 2016

Devices capable of releasing two different small molecules independently, at defined release kinetics, were prepared and their behavior characterized.
Mn(ii) silver-aptamer clusters for targeted MR imaging of tumors
Authors: Mu Wei-Yu , Xiao Xin-Xin , Chen Tian-Tian , Chen Qiu-Yun
Published: July 2016

Mn(ii)-aptamer based nanoclusters are multi-aptamer based targeted MRI agents for cancer MRI diagnosis both in vitro and in vivo.
HAp incorporated ultrafine polymeric fibers with shape memory effect for potential use in bone screw hole healing
Authors: Bao Min , Wang Xianliu , Yuan Huihua , Lou Xiangxin , Zhao Qinghua , Zhang Yanzhong
Published: July 2016

HAp nanoparticle incorporated PLMC nanofibers with enhanced shape memory effect can potentially be used for bone screw hole healing.
Strategies for Teachers to Manage Stuttering in the Classroom: A Call for Research
Authors: Davidow Jason H. , Zaroogian Lisa , Garcia-Barrera Mauricio A.
Published: July 2016

Purpose

This clinical focus article highlights the need for future research involving ways to assist children who stutter in the classroom.

Method

The 4 most commonly recommended strategies for teachers were found via searches of electronic databases and personal libraries of the authors. The peer-reviewed evidence for each recommendation was subsequently located and detailed.

Results

There are varying amounts of evidence for the 4 recommended teacher strategies outside of the classroom, but there are no data for 2 of the strategies, and minimal data for the others, in a classroom setting. That is, there is virtually no evidence regarding whether or not the actions put forth influence, for example, stuttering frequency, stuttering severity, participation, or the social, emotional, and cognitive components of stuttering in the classroom.

Conclusion

There is a need for researchers and speech-language pathologists in the schools to study the outcomes of teacher strategies in the classroom for children who stutter.