bluuebunny/crossref_metadata_2025 huggingface dataset:
Invisible Women? Comparing Candidates’ News Coverage in Europe
Authors: Lühiste Maarja , Banducci Susan
Published: May 2016

Past studies, largely based on the United States, have argued that differential coverage of men and women candidates could explain the lack of women in elected political office. We investigate, first, whether a gender bias exists in coverage of candidates and, second, the possible mechanisms underlying any differences in the amount and tone of candidates’ news media coverage. Using data from the 2009 European Election Study Media Analysis, drawn from media coverage in 25 EU member states during the European Parliament election campaigns, we find that, similar to previous research, there is evidence of a gender gap in the amount of media coverage. Even for highly prominent and competitive candidates, the gender bias in media coverage remains. However, this bias in media coverage largely reflects the parties’ preselection of viable candidates and that where there are remedies in place to address the underrepresentation of women (i.e., quotas), women candidates actually have lower visibility in campaign coverage. We also find that, though women candidates are more often the subject of valence evaluations in news stories, male candidates are more negatively evaluated in news stories.
Stuck in the Basement: A Pathway Case Analysis of Female Recruitment in Hungary's 2010 National Assembly Elections
Authors: Montgomery Kathleen A. , Ilonszki Gabriella
Published: May 2016

Women's legislative underrepresentation has emerged as perhaps the most stable feature of the postcommunist Hungarian political system, resisting Europeanization, changes in the electoral and party systems, and a new constitution. Early research on the decline in women's access to power in postcommunist transitional democracies focused on common legacies of communist rule, but those legacies cannot account for widening disparities in women's representation across the region over time or the persistent underrepresentation of women in Hungary. Using a pathway case analysis of Hungary's 2010 parliamentary elections, this research examines how cultural, structural, and institutional factors interacted to keep Hungary stuck in the basement with respect to women's legislative recruitment.
Do Women and Men Respond Differently to Negative News?
Authors: Soroka Stuart , Gidengil Elisabeth , Fournier Patrick , Nir Lilach
Published: May 2016

This article offers a new approach to studying sex differences in responses to negative news, using real-time physiological responses as opposed to self-reports. Measurements of skin conductance and heart rate are used to examine whether there are differences in the extent to which women and men are aroused by and attentive to negative news stories. Like experiments that have relied on postexposure self-reports, we detect no sex differences in arousal in response to negative news stories. However, in contrast to those experiments, we find indications that women are more attentive than men to negative news content. We consider possible reasons for this difference in findings. We also discuss neuropsychological studies that are consistent with our finding of greater attentiveness on the part of women to negative stimuli. Finally, we consider the relationship between our work and evidence in the literature that women consume less news than men.
Norway and Cuba Evaluate Bilateral Climate Research Results
Authors: Antuña-Marrero Juan , Mesquita Michel , Rodriguez Albeth
Published: May 2016

XCUBE Workshop; Camagüey, Cuba, 16–18 November 2015
U.S. Arctic Leader: With Shell Oil out, Arctic Lost Attention
Authors: Showstack Randy
Published: May 2016

Shell's drilling activities in the Arctic drew the world's eyes to the far north and to issues like climate change and oil spills, the U.S. special representative for the Arctic said in a recent talk.
Th17 cell differentiation proceeds independently of IRF8
Authors: Newman Dane M , Leung Patrick SK , Putoczki Tracy L , Nutt Stephen L , Cretney Erika
Published: May 2016

The transcriptional repressor/activator interferon regulatory factor 8 (IRF8) modulates the differentiation of a multitude of hematopoietic lineages. However, the role of IRF8 in CD4+ T‐cell development is less well defined, with a recent study implicating IRF8 as an intrinsic repressor of interleukin‐17 (IL‐17) expressing T helper type 17 (Th17) cell differentiation. Using an IRF8‐EGFP reporter strain we have confirmed that IRF8 is expressed in all T helper lineages, including Th17 cells. The loss of IRF8 did not affect Th17 differentiation in vitro, beyond a small increase in IL‐22 expression. Moreover, IRF8 deficiency did not enhance the Th17 immune response in experimental T‐cell transfer colitis. Together, these results suggest that IRF8 does not play an essential intrinsic role in Th17 cell differentiation.
Experimental evolution reveals that high relatedness protects multicellular cooperation from cheaters
Authors: Bastiaans Eric , Debets Alfons J. M. , Aanen Duur K.
Published: May 2016

In multicellular organisms, there is a potential risk that cheating mutants gain access to the germline. Development from a single-celled zygote resets relatedness among cells to its maximum value each generation, which should accomplish segregation of cheating mutants from non-cheaters and thereby protect multicellular cooperation. Here we provide the crucial direct comparison between high- and low-relatedness conditions to test this hypothesis. We allow two variants of the fungus Neurospora crassa to evolve, one with and one without the ability to form chimeras with other individuals, thus generating two relatedness levels. While multicellular cooperation remains high in the high-relatedness lines, it significantly decreases in all replicate low-relatedness lines, resulting in an average threefold decrease in spore yield. This reduction is caused by cheating mutants with reduced investment in somatic functions, but increased competitive success when fusing with non-cheaters. Our experiments demonstrate that high genetic relatedness is crucial to sustain multicellular cooperation.
Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder
Authors: Severance Emily G , Gressitt Kristin L , Stallings Catherine R , Katsafanas Emily , Schweinfurth Lucy A , Savage Christina L , Adamos Maria B , Sweeney Kevin M , Origoni Andrea E , Khushalani Sunil , Leweke F Markus , Dickerson Faith B , Yolken Robert H
Published: May 2016

Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut–brain mechanisms.
Phase-factor-dependent symmetries and quantum phases in a three-level cavity QED system
Authors: Fan Jingtao , Yu Lixian , Chen Gang , Jia Suotang
Published: May 2016

Unlike conventional two-level particles, three-level particles may support some unitary-invariant phase factors when they interact coherently with a single-mode quantized light field. To gain a better understanding of light-matter interaction, it is thus necessary to explore the phase-factor-dependent physics in such a system. In this report, we consider the collective interaction between degenerate V-type three-level particles and a single-mode quantized light field, whose different components are labeled by different phase factors. We mainly establish an important relation between the phase factors and the symmetry or symmetry-broken physics. Specifically, we find that the phase factors affect dramatically the system symmetry. When these symmetries are breaking separately, rich quantum phases emerge. Finally, we propose a possible scheme to experimentally probe the predicted physics of our model. Our work provides a way to explore phase-factor-induced nontrivial physics by introducing additional particle levels.
Efficient generation of FVII gene knockout mice using CRISPR/Cas9 nuclease and truncated guided RNAs
Authors: An Liyou , Hu Yeshu , Chang Shiwei , Zhu Xiumei , Ling Pingping , Zhang Fenli , Liu Jiao , Liu Yanhong , Chen Yexiang , Yang Lan , Presicce Giorgio Antonio , Du Fuliang
Published: May 2016

We investigated the effects of 5′-end truncated CRISPR RNA-guided Cas9 nuclease (tru-RGN, 17/18 nucleotides) on genome editing capability in NIH/3T3 cells, and its efficiencies on generating Factor VII (FVII) gene-knockout (KO) mice. In cultured cells, RGNs on-target editing activity had been varied when gRNAs was truncated, higher at Site Two (tF7–2 vs. F7–2, 49.5 vs. 30.1%) while lower in other two sites (Site One, tF7–1 vs.F7–1, 12.1 vs. 23.6%; Site Three, tF7–3 vs.F7–3, 7.7 vs 10.9%) (P < 0.05). Out of 15 predicated off–target sites, tru-RGNs showed significantly decreased frequencies at 5 sites. By microinjecting tru-RGN RNAs into zygotes, FVII KO mice were generated with higher efficiency at Site Two (80.1 vs. 35.8%) and Site One (55.0 vs 3.7%) (P < 0.05), but not at Site three (39.4 vs 27.8%) (P > 0.05) when compared with standard RGN controls. Knockout FVII mice demonstrated a delayed prothrombin time and decreased plasma FVII expression. Our study first demonstrates that truncated gRNAs to 18 complementary nucleotides and Cas9 nucleases, can effectively generate FVII gene KO mice with a significantly higher efficiency in a site-dependent manner. In addition, the off-target frequency was much lower in KO mice than in cell lines via RGN expression vector-mediated genome editing.
Species and Media Effects on Soil Carbon Dynamics in the Landscape
Authors: Marble S. Christopher , Prior Stephen A. , Runion G. Brett , Torbert H. Allen , Gilliam Charles H. , Fain Glenn B. , Sibley Jeff L. , Knight Patricia R.
Published: May 2016

Three woody shrub species [cleyera (Ternstroemia gymnanthera Thunb. ‘Conthery’), Indian hawthorn (Rhaphiolepis indica L.) and loropetalum (Loropetalum chinensis Oliv.‘Ruby’)] were container-grown for one growing season in 2008 using either pinebark (industry standard), clean chip residual or WholeTree (derived by-products from the forestry industry) as potting substrates and then transplanted into the landscape in 2008. An Automated Carbon Efflux System was used to continually monitor soil CO2 efflux from December 2010 through November 2011 in each species and substrate combination. Changes in soil carbon (C) levels as a result of potting substrate were assessed through soil sampling in 2009 and 2011 and plant biomass was determined at study conclusion. Results showed that soil CO2-C efflux was similar among all species and substrates, with few main effects of species or substrate observed throughout the study. Soil analysis showed that plots with pinebark contained higher levels of soil C in both 2009 and 2011, suggesting that pinebark decomposes slower than clean chip residual or WholeTree and consequently has greater C storage potential than the two alternative substrates. Results showed a net C gain for all species and substrate combinations; however, plants grown in pinebark had greater C sequestration potential.
Posing for a picture: vesicle immobilization in agarose gel
Authors: Lira Rafael B. , Steinkühler Jan , Knorr Roland L. , Dimova Rumiana , Riske Karin A.
Published: May 2016

Taking a photo typically requires the object of interest to stand still. In science, imaging is potentiated by optical and electron microscopy. However, living and soft matter are not still. Thus, biological preparations for microscopy usually include a fixation step. Similarly, immobilization strategies are required for or substantially facilitate imaging of cells or lipid vesicles and even more so for acquiring high-quality data via fluorescence-based techniques. Here, we describe a simple yet efficient method to immobilize objects such as lipid vesicles with sizes between 0.1 and 100 μm using agarose gel. We show that while large and giant unilamellar vesicles (LUVs and GUVs) can be caged in the pockets of the gel meshwork, small molecules, proteins and micelles remain free to diffuse through the gel and interact with membranes as in agarose-free solutions and complex biochemical reactions involving several proteins can proceed in the gel. At the same time, immobilization in agarose has no adverse effect on the GUV size and stability. By applying techniques such as FRAP and FCS, we show that the lateral diffusion of lipids is not affected by the gel. Finally, our immobilization strategy allows capturing high-resolution 3D images of GUVs.
Inhibiting DNA methylation switches adipogenesis to osteoblastogenesis by activating Wnt10a
Authors: Chen Yii-Shyuan , Wu Rui , Yang Xiaosong , Kou Shuping , MacDougald Ormond A. , Yu Liqing , Shi Hang , Xue Bingzhong
Published: May 2016

Both adipocytes and osteoblasts share the mesodermal lineage that derives from mesenchymal stem cells. Most studies investigating the mechanisms underlying the regulation of adipogenic or osteoblastogenic development focus on transcriptional pathways; little is known about the epigenetic mechanisms in this process. We thus determined the role of 5-aza-2′-deoxycytidine (5-Aza-dC), an inhibitor of DNA methylation, in the lineage determination between adipogenesis and osteoblastogenesis. Inhibiting DNA methylation in 3T3-L1 preadipocytes by 5-Aza-dC significantly inhibited adipogenesis whereas promoted osteoblastogenesis. This dual effect of 5-Aza-dC was associated with up-regulation of Wnt10a, a key factor determining the fate of the mesenchymal lineage towards osteoblasts. Consistently, IWP-2, an inhibitor of Wnt proteins, was found to prevent the anti-adipogenic effect of 5-Aza-dC in 3T3-L1 preadipocytes and block the osteoblastogenic effect of 5-Aza-dC in ST2 mesenchymal stem cell line. Finally, the Wnt10a 5′-region is enriched with CpG sites, whose methylation levels were markedly reduced by 5-Aza-dC. Thus we conclude that inhibiting DNA methylation by 5-Aza-dC mutual-exclusively regulates the lineage determination of adipogenesis and osteoblastogenesis by demethylating Wnt10a gene and upregulating its expression. Our study defines DNA methylation as a novel mechanism underlying adipocyte and bone cell development.
The antibodies against 5-bromo-2′-deoxyuridine specifically recognize trifluridine incorporated into DNA
Authors: Kitao Hiroyuki , Morodomi Yosuke , Niimi Shinichiro , Kiniwa Mamoru , Shigeno Kazuhiko , Matsuoka Kazuaki , Kataoka Yuki , Iimori Makoto , Tokunaga Eriko , Saeki Hiroshi , Oki Eiji , Maehara Yoshihiko
Published: May 2016

Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102 (also named TFTD), which consists of FTD and a thymidine phosphorylase inhibitor. FTD is supposed to exert its cytotoxicity via massive misincorporation into DNA, but the underlying mechanism of FTD incorporation into DNA and its correlation with cytotoxicity are not fully understood. The present study shows that several antibodies against 5-bromo-2′-deoxyuridine (BrdU) specifically cross-react with FTD, either anchored to bovine serum albumin or incorporated into DNA. These antibodies are useful for several biological applications, such as fluorescence-activated cell sorting, fluorescent immunostaining and immunogold detection for electron microscopy. These techniques confirmed that FTD is mainly incorporated in the nucleus during S phase in a concentration-dependent manner. In addition, FTD was also detected by immunohistochemical staining in paraffin-embedded HCT-116 xenograft tumors after intraperitoneal administration of FTD. Intriguingly, FTD was hardly detected in surrounding matrices, which consisted of fibroblasts with marginal expression of the nucleoside transporter genes SLC29A1 and SLC29A2. Thus, applications using anti-BrdU antibodies will provide powerful tools to unveil the underlying mechanism of FTD action and to predict or evaluate the efficacy and adverse effects of TAS-102 clinically.
HpDTC1, a Stress-Inducible Bifunctional Diterpene Cyclase Involved in Momilactone Biosynthesis, Functions in Chemical Defence in the Moss Hypnum plumaeforme
Authors: Okada Kazunori , Kawaide Hiroshi , Miyamoto Koji , Miyazaki Sho , Kainuma Ryosuke , Kimura Honoka , Fujiwara Kaoru , Natsume Masahiro , Nojiri Hideaki , Nakajima Masatoshi , Yamane Hisakazu , Hatano Yuki , Nozaki Hiroshi , Hayashi Ken-ichiro
Published: May 2016

Momilactones, which are diterpenoid phytoalexins with antimicrobial and allelopathic functions, have been found only in rice and the moss Hypnum plumaeforme. Although these two evolutionarily distinct plant species are thought to produce momilactones as a chemical defence, the momilactone biosynthetic pathway in H. plumaeforme has been unclear. Here, we identified a gene encoding syn-pimara-7,15-diene synthase (HpDTC1) responsible for the first step of momilactone biosynthesis in the moss. HpDTC1 is a bifunctional diterpene cyclase that catalyses a two-step cyclization reaction of geranylgeranyl diphosphate to syn-pimara-7,15-diene. HpDTC1 transcription was up-regulated in response to abiotic and biotic stress treatments. HpDTC1 promoter-GUS analysis in transgenic Physcomitrella patens showed similar transcriptional responses as H. plumaeforme to the stresses, suggesting that a common response system to stress exists in mosses. Jasmonic acid (JA), a potent signalling molecule for inducing plant defences, could not activate HpDTC1 expression. In contrast, 12-oxo-phytodienoic acid, an oxylipin precursor of JA in vascular plants, enhanced HpDTC1 expression and momilactone accumulation, implying that as-yet-unknown oxylipins could regulate momilactone biosynthesis in H. plumaeforme. These results demonstrate the existence of an evolutionarily conserved chemical defence system utilizing momilactones and suggest the molecular basis of the regulation for inductive production of momilactones in H. plumaeforme.
Erratum: Mimicking titration experiments with MD simulations: A protocol for the investigation of pH-dependent effects on proteins
Authors: Socher Eileen , Sticht Heinrich
Published: May 2016

Scientific Reports 6: Article number: 22523; Published online: 03 March 2016; Updated: 03 May 2016 This Article contains errors in Equation 1. should read:
Giant electric-field-induced strain in lead-free piezoelectric materials
Authors: Chen Lan , Yang Yurong , Meng X. K.
Published: May 2016

First-principles calculations are performed to investigate the structures, electrical, and magnetic properties of compressive BiFeO3 films under electric-field and pressure perpendicular to the films. A reversible electric-field-induced strain up 10% is achieved in the compressive BiFeO3 films. The giant strain originates from rhombohedral-tetragonal (R-T) phase transition under electric-filed, and is recoverable from tetragonal-rhombohedral (T-R) phase transition by compressive stress. Additionally, the weak ferromagnetism in BiFeO3 films is largely changed in R-T phase transition under electric-filed and T-R phase transition under pressure – reminiscent of magnetoelectric effect and magnetoelastic effect. These results suggest exciting device opportunities arising from the giant filed-induced strain, large magnetoelectric effect and magnetoelastic effect.
Stretchable Binary Fresnel Lens for Focus Tuning
Authors: Li Xueming , Wei Lei , Poelma René H. , Vollebregt Sten , Wei Jia , Urbach Hendrik Paul , Sarro Pasqualina M. , Zhang Guo Qi
Published: May 2016

This paper presents a tuneable binary amplitude Fresnel lens produced by wafer-level microfabrication. The Fresnel lens is fabricated by encapsulating lithographically defined vertically aligned carbon nanotube (CNT) bundles inside a polydimethyl-siloxane (PDMS) layer. The composite lens material combines the excellent optical absorption properties of the CNT with the transparency and stretchability of the PDMS. By stretching the elastomeric composite in radial direction, the lens focal length is tuned. Good focusing response is demonstrated and a large focus change (≥24%) was achieved by stretching lenses up to 11.4%.
Critical Role of Diels–Adler Adducts to Realise Stretchable Transparent Electrodes Based on Silver Nanowires and Silicone Elastomer
Authors: Heo Gaeun , Pyo Kyoung-hee , Lee Da Hee , Kim Youngmin , Kim Jong-Woong
Published: May 2016

This paper presents the successful fabrication of a transparent electrode comprising a sandwich structure of silicone/Ag nanowires (AgNWs)/silicone equipped with Diels–Alder (DA) adducts as crosslinkers to realise highly stable stretchability. Because of the reversible DA reaction, the crosslinked silicone successfully bonds with the silicone overcoat, which should completely seal the electrode. Thus, any surrounding liquid cannot leak through the interfaces among the constituents. Furthermore, the nanowires are protected by the silicone cover when they are stressed by mechanical loads such as bending, folding and stretching. After delicate optimisation of the layered silicone/AgNW/silicone sandwich structure, a stretchable transparent electrode which can withstand 1000 cycles of 50% stretching–releasing with an exceptionally high stability and reversibility was fabricated. This structure can be used as a transparent strain sensor; it possesses a strong piezoresistivity with a gauge factor greater than 11.
Quantitative evaluation of fiber fuse initiation with exposure to arc discharge provided by a fusion splicer
Authors: Todoroki Shin-ichi
Published: May 2016

The optical communication industry and power-over-fiber applications face a dilemma as a result of the expanding demand of light power delivery and the potential risks of high-power light manipulation including the fiber fuse phenomenon, a continuous destruction of the fiber core pumped by the propagating light and triggered by a heat-induced strong absorption of silica glass. However, we have limited knowledge on its initiation process in the viewpoint of energy flow in the reactive area. Therefore, the conditions required for a fiber fuse initiation in standard single-mode fibers were determined quantitatively, namely the power of a 1480 nm fiber laser and the arc discharge intensity provided by a fusion splicer for one second as an outer heat source. Systematic investigation on the energy flow balance between these energy sources revealed that the initiation process consists of two steps; the generation of a precursor at the heated spot and the transition to a stable fiber fuse. The latter step needs a certain degree of heat accumulation at the core where waveguide deformation is ongoing competitively. This method is useful for comparing the tolerance to fiber fuse initiation among various fibers with a fixed energy amount that was not noticed before.
Up-regulation of Interferon-inducible protein 16 contributes to psoriasis by modulating chemokine production in keratinocytes
Authors: Cao Tianyu , Shao Shuai , Li Bing , Jin Liang , Lei Jie , Qiao Hongjiang , Wang Gang
Published: May 2016

Psoriasis is a common chronic inflammatory skin disease characterized by epidermal hyperplasia and dermal inflammation. Keratinocyte activation is known to play a critical role in psoriasis, but the underlying mechanism remains unclear. Interferon-inducible protein 16 (IFI16), an innate immune system sensor, is reported to affect keratinocyte function. We therefore hypothesized that IFI16 promotes psoriasis by modulating keratinocyte activation. In the present study, we cinfirmed that IFI16 was overexpressed in epidermal keratinocytes of psoriasis patients. In addition, psoriasis-related cytokines, including IFN-γ, TNF-α, IL-17 and IL-22, induced IFI16 up-regulation in keratinocytes via activation of STAT3 signaling. We also observed that IFI16 activated the TBK1-NF-κB signaling, leading to the production of CXCL10 and CCL20. Importantly, knocking down p204, which is reported as the mouse orthologous of human IFI16, inhibited epidermal hyperplasia in mice with imiquimod-induced psoriasiform dermatitis. These findings indicate that IFI16 plays a critical role in the pathogenesis of psoriasis and may be a potential therapeutic target.
The Association between Resting Functional Connectivity and Visual Creativity
Authors: Li Wenfu , Yang Junyi , Zhang Qinglin , Li Gongying , Qiu Jiang
Published: May 2016

Resting-state functional connectivity (RSFC), the temporal correlation of intrinsic activation between different brain regions, has become one of the most fascinating field in the functional imaging studies. To better understand the association between RSFC and individual creativity, we used RSFC and the figure Torrance Tests of Creative Thinking (TTCT-F) to investigate the relationship between creativity measured by TTCT and RSFC within two different brain networks, default mode network and the cognitive control network, in a large healthy sample (304). We took the medial prefrontal cortex (MPFC) and the bilateral dorsolateral prefrontal cortices (DLPFC) to be the seed regions and investigated the association across subjects between the score of TTCT-F and the strength of RSFC between these seed regions and other voxels in the whole brain. Results revealed that the strength of RSFC with the MPFC was significantly and negatively correlated with the score of TTCT-F in the precuneus. Meanwhile, we also found that the strength of RSFC with the left DLPFC was significantly and positively correlated with the score of TTCT-F in the right DLPFC. It suggests that the decreased RSFC within DMN and the increased RSFC within CCN presents a potential interaction mechanism between different region for higher creativity.
Influence of DNA extraction methods on relative telomere length measurements and its impact on epidemiological studies
Authors: Raschenberger Julia , Lamina Claudia , Haun Margot , Kollerits Barbara , Coassin Stefan , Boes Eva , Kedenko Ludmilla , Köttgen Anna , Kronenberg Florian
Published: May 2016

Measurement of telomere length is widely used in epidemiologic studies. Insufficient standardization of the measurements processes has, however, complicated the comparison of results between studies. We aimed to investigate whether DNA extraction methods have an influence on measured values of relative telomere length (RTL) and whether this has consequences for epidemiological studies. We performed four experiments with RTL measurement in quadruplicate by qPCR using DNA extracted with different methods: 1) a standardized validation experiment including three extraction methods (magnetic-particle-method EZ1, salting-out-method INV, phenol-chloroform-isoamyl-alcohol PCI) each in the same 20 samples demonstrated pronounced differences in RTL with lowest values with EZ1 followed by INV and PCI-isolated DNA; 2) a comparison of 307 samples from an epidemiological study showing EZ1-measurements 40% lower than INV-measurements; 3) a matching-approach of two similar non-diseased control groups including 143 pairs of subjects revealed significantly shorter RTL in EZ1 than INV-extracted DNA (0.844 ± 0.157 vs. 1.357 ± 0.242); 4) an association analysis of RTL with prevalent cardiovascular disease detected a stronger association with INV than with EZ1-extracted DNA. In summary, DNA extraction methods have a pronounced influence on the measured RTL-values. This might result in spurious or lost associations in epidemiological studies under certain circumstances.
A gain-of-function ACTC1 3′UTR mutation that introduces a miR-139-5p target site may be associated with a dominant familial atrial septal defect
Authors: Wang Ye , Du Xinwei , Zhou Zaiwei , Jiang Jun , Zhang Zhen , Ye Lincai , Hong Haifa
Published: May 2016

The ostium secundum atrial septal defect (ASDII) is the most common type of congenital heart disease and is characterized by a left to right shunting of oxygenated blood caused by incomplete closure of the septum secundum. We identified a familial form of isolated ASDII that affects four individuals in a family of five and shows autosomal dominant inheritance. By whole genome sequencing, we discovered a new mutation (c.*1784T > C) in the 3′-untranslated region (3′UTR) of ACTC1, which encodes the predominant actin in the embryonic heart. Further analysis demonstrated that the c.*1784T > C mutation results in a new target site for miRNA-139-5p, a microRNA that is involved in cell migration, invasion, and proliferation. Functional analysis demonstrated that the c.*1784T > C mutation specifically downregulates gene expression in a luciferase assay. Additionally, miR-139-5p mimic causes further decrease, whereas miR-139-5p inhibitor can dramatically rescue the decline in gene expression caused by this mutation. These findings suggest that the familial ASDII may be a result of an ACTC1 3′UTR gain-of-function mutation caused by the introduction of a new miR-139-5p target site. Our results provide the first evidence of a pathogenic mutation in the ACTC1 3′UTR that may be associated with familial isolated ASDII.
Coupled grain boundary motion in aluminium: the effect of structural multiplicity
Authors: Cheng Kuiyu , Zhang Liang , Lu Cheng , Tieu Kiet
Published: May 2016

The shear-induced coupled grain boundary motion plays an important role in the deformation of nanocrystalline (NC) materials. It has been known that the atomic structure of the grain boundary (GB) is not necessarily unique for a given set of misorientation and inclination of the boundary plane. However, the effect of the structural multiplicity of the GB on its coupled motion has not been reported. In the present study we investigated the structural multiplicity of the symmetric tilt Σ5(310) boundary in aluminium and its influence on the GB behaviour at a temperature range of 300 K–600 K using molecular dynamic simulations. Two starting atomic configurations were adopted in the simulations which resulted in three different GB structures at different temperatures. Under the applied shear deformation each GB structure exhibited its unique GB behaviour. A dual GB behaviour, namely the transformation of one GB behaviour to another during deformation, was observed for the second starting configuration at a temperature of 500 K. The atomistic mechanisms responsible for these behaviour were analysed in detail. The result of this study implicates a strong relationship between GB structures and their behaviour and provides a further information of the grain boundary mediated plasticity in nanocrystalline materials.
Vacancy Structures and Melting Behavior in Rock-Salt GeSbTe
Authors: Zhang Bin , Wang Xue-Peng , Shen Zhen-Ju , Li Xian-Bin , Wang Chuan-Shou , Chen Yong-Jin , Li Ji-Xue , Zhang Jin-Xing , Zhang Ze , Zhang Sheng-Bai , Han Xiao-Dong
Published: May 2016

Ge-Sb-Te alloys have been widely used in optical/electrical memory storage. Because of the extremely fast crystalline-amorphous transition, they are also expected to play a vital role in next generation nonvolatile microelectronic memory devices. However, the distribution and structural properties of vacancies have been one of the key issues in determining the speed of melting (or amorphization), phase-stability and heat-dissipation of rock-salt GeSbTe, which is crucial for its technological breakthrough in memory devices. Using spherical aberration-aberration corrected scanning transmission electron microscopy and atomic scale energy-dispersive X-ray mapping, we observe a new rock-salt structure with high-degree vacancy ordering (or layered-like ordering) at an elevated temperature, which is a result of phase transition from the rock-salt phase with randomly distributed vacancies. First-principles calculations reveal that the phase transition is an energetically favored process. Moreover, molecular dynamics studies suggest that the melting of the cubic rock-salt phases is initiated at the vacancies, which propagate to nearby regions. The observation of multi-rock-salt phases suggests another route for multi-level data storage using GeSbTe.
Evaluation of the diagnostic value of 64 simultaneously measured autoantibodies for early detection of gastric cancer
Authors: Werner Simone , Chen Hongda , Butt Julia , Michel Angelika , Knebel Phillip , Holleczek Bernd , Zörnig Inka , Eichmüller Stefan B. , Jäger Dirk , Pawlita Michael , Waterboer Tim , Brenner Hermann
Published: May 2016

Autoantibodies against tumor-associated antigens (TAAs) have been suggested as biomarkers for early detection of gastric cancer. However, studies that systematically assess the diagnostic performance of a large number of autoantibodies are rare. Here, we used bead-based multiplex serology to simultaneously measure autoantibody responses against 64 candidate TAAs in serum samples from 329 gastric cancer patients, 321 healthy controls and 124 participants with other diseases of the upper digestive tract. At 98% specificity, sensitivities for the 64 tested autoantibodies ranged from 0–12% in the training set and a combination of autoantibodies against five TAAs (MAGEA4 + CTAG1 + TP53 + ERBB2_C + SDCCAG8) was able to detect 32% of the gastric cancer patients at a specificity of 87% in the validation set. Sensitivities for early and late stage gastric cancers were similar, while chronic atrophic gastritis, a precursor lesion of gastric cancer, was not detectable. However, the 5-marker combination also detected 26% of the esophageal cancer patients. In conclusion, the tested autoantibodies and combinations alone did not reach sufficient sensitivity for gastric cancer screening. Nevertheless, some autoantibodies, such as anti-MAGEA4, anti-CTAG1 or anti-TP53 and their combinations could possibly contribute to the development of cancer early detection tests (not necessarily restricted to gastric cancer) when being combined with other markers.
Long-chain bases of sphingolipids are transported into cells via the acyl-CoA synthetases
Authors: Narita Tomomi , Naganuma Tatsuro , Sase Yurie , Kihara Akio
Published: May 2016

Transport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for their transports. Sodium azide/2-deoxy-D-glucose treatment inhibited import of LCFA but not that of LCB. Furthermore, the ATP-AMP motif mutation FAA1 S271A largely impaired the metabolic activity and LCFA uptake, while leaving LCB import unaffected. These results indicate that only LCFA transport requires ATP. Since ACSs do not metabolize LCBs as substrates, Faa1 and Faa4 are likely directly involved in LCB transport. Furthermore, we revealed that ACSs are also involved in LCB transport in mammalian cells. Thus, our findings provide strong support for the hypothesis that ACSs directly transport LCFAs.
Dynamic cutaneous information is sufficient for precise curvature discrimination
Authors: Cheeseman Jacob R. , Norman J. Farley , Kappers Astrid M. L.
Published: May 2016

Our tactual perceptual experiences occur when we interact, actively and passively, with environmental objects and surfaces. Previous research has demonstrated that active manual exploration often enhances the tactual perception of object shape. Nevertheless, the factors that contribute to this enhancement are not well understood. The present study evaluated the ability of 28 younger (mean age was 23.1 years) and older adults (mean age was 71.4 years) to discriminate curved surfaces by actively feeling objects with a single index finger and by passively feeling objects that moved relative to a restrained finger. While dynamic cutaneous stimulation was therefore present in both conditions, active exploratory movements only occurred in one. The results indicated that there was a significant and large effect of age, such that the older participants’ thresholds were 43.8 percent higher than those of the younger participants. Despite the overall adverse effect of age, the pattern of results across the active and passive touch conditions was identical. For both age groups, the curvature discrimination thresholds obtained for passive touch were significantly lower than those that occurred during active touch. Curvature discrimination performance was therefore best in the current study when dynamic cutaneous stimulation occurred in the absence of active movement.
Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal
Authors: Risso Davide S. , Mezzavilla Massimo , Pagani Luca , Robino Antonietta , Morini Gabriella , Tofanelli Sergio , Carrai Maura , Campa Daniele , Barale Roberto , Caradonna Fabio , Gasparini Paolo , Luiselli Donata , Wooding Stephen , Drayna Dennis
Published: May 2016

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.
Schizophrenia and subsequent neighborhood deprivation: revisiting the social drift hypothesis using population, twin and molecular genetic data
Authors: Sariaslan A , Fazel S , D'Onofrio B M , Långström N , Larsson H , Bergen S E , Kuja-Halkola R , Lichtenstein P
Published: May 2016

Neighborhood influences in the etiology of schizophrenia have been emphasized in a number of systematic reviews, but causality remains uncertain. To test the social drift hypothesis, we used three complementary genetically informed Swedish cohorts. First, we used nationwide Swedish data on approximately 760 000 full- and half-sibling pairs born between 1951 and 1974 and quantitative genetic models to study genetic and environmental influences on the overlap between schizophrenia in young adulthood and subsequent residence in socioeconomically deprived neighborhoods. Schizophrenia diagnoses were ascertained using the National Patient Registry. Second, we tested the overlap between childhood psychotic experiences and neighborhood deprivation in early adulthood in the longitudinal Twin Study of Child and Adolescent Development (TCHAD; n=2960). Third, we investigated to what extent polygenic risk scores for schizophrenia predicted residence in deprived neighborhoods during late adulthood using the TwinGene sample (n=6796). Sibling data suggested that living in deprived neighborhoods was substantially heritable; 65% (95% confidence interval (95% CI): 60–71%) of the variance was attributed to genetic influences. Although the correlation between schizophrenia and neighborhood deprivation was moderate in magnitude (r=0.22; 95% CI: 0.20–0.24), it was entirely explained by genetic influences. We replicated these findings in the TCHAD sample. Moreover, the association between polygenic risk for schizophrenia and neighborhood deprivation was statistically significant (R2=0.15%, P=0.002). Our findings are primarily consistent with a genetic selection interpretation where genetic liability for schizophrenia also predicts subsequent residence in socioeconomically deprived neighborhoods. Previous studies may have overemphasized the relative importance of environmental influences in the social drift of schizophrenia patients. Clinical and policy interventions will therefore benefit from the future identification of potentially causal pathways between different dimensions of cognitive functions and socioeconomic trajectories derived from studies adopting family-based research designs.
Physical activity delays hippocampal neurodegeneration and rescues memory deficits in an Alzheimer disease mouse model
Authors: Hüttenrauch M , Brauß A , Kurdakova A , Borgers H , Klinker F , Liebetanz D , Salinas-Riester G , Wiltfang J , Klafki H W , Wirths O
Published: May 2016

The evidence for a protective role of physical activity on the risk and progression of Alzheimer’s disease (AD) has been growing in the last years. Here we studied the influence of a prolonged physical and cognitive stimulation on neurodegeneration, with special emphasis on hippocampal neuron loss and associated behavioral impairment in the Tg4-42 mouse model of AD. Tg4-42 mice overexpress Aβ4-42 without any mutations, and develop an age-dependent hippocampal neuron loss associated with a severe memory decline. We demonstrate that long-term voluntary exercise diminishes CA1 neuron loss and completely rescues spatial memory deficits in different experimental settings. This was accompanied by changes in the gene expression profile of Tg4-42 mice. Deep sequencing analysis revealed an upregulation of chaperones involved in endoplasmatic reticulum protein processing, which might be intimately linked to the beneficial effects seen upon long-term exercise. We believe that we provide evidence for the first time that enhanced physical activity counteracts neuron loss and behavioral deficits in a transgenic AD mouse model. The present findings underscore the relevance of increased physical activity as a potential strategy in the prevention of dementia.
HPA-axis function and grey matter volume reductions: imaging the diathesis-stress model in individuals at ultra-high risk of psychosis
Authors: Valli I , Crossley N A , Day F , Stone J , Tognin S , Mondelli V , Howes O , Valmaggia L , Pariante C , McGuire P
Published: May 2016

The onset of psychosis is thought to involve interactions between environmental stressors and the brain, with cortisol as a putative mediator. We examined the relationship between the cortisol stress response and brain structure in subjects at ultra-high risk (UHR) for psychosis. Waking salivary cortisol was measured in 22 individuals at UHR for psychosis and 17 healthy controls. Grey matter volume was assessed using magnetic resonance imaging at 3 T. The relationship between the stress response and grey matter volume was investigated using voxel-based analyses. Our predictions of the topography of cortisol action as a structural brain modulator were informed by measures of brain glucocorticoid and mineralcorticoid receptor distribution obtained from the multimodal neuroanatomical and genetic Allen Brain Atlas. Across all subjects, reduced responsivity of the hypothalamus–pituitary–adrenal (HPA) axis was correlated with smaller grey matter volumes in the frontal, parietal and temporal cortex and in the hippocampus. This relationship was particularly marked in the UHR subjects in the right prefrontal, left parahippocampal/fusiform and parietal cortices. The subgroup that subsequently developed psychosis showed a significant blunting of HPA stress response, observed at trend level also in the whole UHR sample. Altered responses to stress in people at high risk of psychosis are related to reductions in grey matter volume in areas implicated in the vulnerability to psychotic disorders. These areas may represent the neural components of a stress vulnerability model.
Synthesis and excellent microwave absorption properties of reduced graphene oxide/FeNi3/Fe3O4 composite
Authors: Luo Hui , Gong Rongzhou , Wang Xian , Song Kai , Zhu Changming , Wang Liguang
Published: May 2016

A ternary spherical composite was synthesized by a solvothermal method and its microwave absorption properties were studied.
Identification of the current path for a conductive molecular wire on a tripodal platform
Authors: Karimi M. A. , Bahoosh S. G. , Valášek M. , Bürkle M. , Mayor M. , Pauly F. , Scheer E.
Published: May 2016

We present charge transport measurements and calculations and outline the chemical synthesis route for a new tripodal platform based on a rigid 9,9′-spirobifluorene equipped with a phenylene-ethynylene wire.
Reduction-responsive modification-induced higher efficiency for attenuation of tumor metastasis of low molecular weight heparin functionalized liposomes
Authors: Tian Jilai , Han Miaomiao , Wang Yue , Qian Kang , Ke Xue , Ci Tianyuan
Published: May 2016

Higher efficiency of attenuation of tumor metastasis was achievedviareduction-responsive modification of low molecular weight heparin on doxorubicin liposomes.
Substantial enhancement of corrosion resistance and bioactivity of magnesium by incorporating calcium silicate particles
Authors: Huan Zhiguang , Xu Chen , Ma Bing , Zhou Jie , Chang Jiang
Published: May 2016

We discovered that calcium silicate is an effective reinforcement phase to improve the corrosion resistance, mechanical strength and biological performance of Mg or Mg-based alloys to overcome their major drawbacks for orthopedic implant applications.
Synthesis of substituted phenylcarbamates of N-cyclobutylformylated chitosan and their application as chiral selectors in enantioseparation
Authors: Zhang Juan , Wang Xiao-Chen , Chen Wei , Bai Zheng-Wu
Published: May 2016

New CSPs exhibited high tolerability to common organic solvents, and most of them possessed excellent enantioseparation capability.
Fluorescence array-based sensing of nitroaromatics using conjugated polyelectrolytes
Authors: Wu Jiatao , Tan Chunyan , Chen Zhifang , Chen Yu Zong , Tan Ying , Jiang Yuyang
Published: May 2016

A sensor array consisting of six conjugated polyelectrolytes was constructed to discriminate between nine nitroaromatics by linear discrimination analysis.