bluuebunny/crossref_metadata_2025 huggingface dataset:
Abrupt stop of deep water turnover with lake warming: Drastic consequences for algal primary producers
Authors: Yankova Yana , Neuenschwander Stefan , Köster Oliver , Posch Thomas
Published: October 2017

After strong fertilization in the 20thcentury, many deep lakes in Central Europe are again nutrient poor due to long-lasting restoration (re-oligotrophication). In line with reduced phosphorus and nitrogen loadings, total organismic productivity decreased and lakes have now historically low nutrient and biomass concentrations. This caused speculations that restoration was overdone and intended fertilizations are needed to ensure ecological functionality. Here we show that recent re-oligotrophication processes indeed accelerated, however caused by lake warming. Rising air temperatures strengthen thermal stabilization of water columns which prevents thorough turnover (holomixis). Reduced mixis impedes down-welling of oxygen rich epilimnetic (surface) and up-welling of phosphorus and nitrogen rich hypolimnetic (deep) water. However, nutrient inputs are essential for algal spring blooms acting as boost for annual food web successions. We show that repeated lack (since 1977) and complete stop (since 2013) of holomixis caused drastic epilimnetic phosphorus depletions and an absence of phytoplankton spring blooms in Lake Zurich (Switzerland). By simulating holomixis in experiments, we could induce significant vernal algal blooms, confirming that there would be sufficient hypolimnetic phosphorus which presently accumulates due to reduced export. Thus, intended fertilizations are highly questionable, as hypolimnetic nutrients will become available during future natural or artificial turnovers.
Association between pulse wave velocity and hot flashes/sweats in middle-aged women
Authors: Yang Ruwei , Zhou Yang , Li Changbin , Tao Minfang
Published: October 2017

As women age and go through menopause, they suffer a higher incidence of cardiovascular morbidity and mortality. Previous studies have shown that a relationship exists between hot flashes/sweats and an increased risk of cardiovascular disease. However, the association between hot flashes/sweats and arterial stiffness is unclear. We aim to explore the relationship between hot flashes/sweats and arterial stiffness using the modified Kupperman index (KMI) questionnaire and measure the brachial-ankle pulse wave velocity (baPWV). The prevalence of hot flashes in our research was reported to be 41.77%. There was a statistically significant difference between the mean baPWV among groups that experienced different severities of hot flashes/sweats according to one-way ANOVA test (p < 0.001). The baPWV values were positively associated with the severity of hot flashes/sweats based on linear regression after adjusting for established cardiovascular confounders (95% CI: (5.86, 43.23), p = 0.01). To the best of our knowledge, this study is the first investigation to propose that baPWV may serve both as an objective index for evaluating the severity of hot flashes/sweats and as a predictor of arterial stiffness beyond Cardiac Vascular Disease (CVD) risk factors in middle-aged women.
The role of EZH2 in overall survival of colorectal cancer: a meta-analysis
Authors: Vilorio-Marqués Laura , Martín Vicente , Diez-Tascón Cristina , González-Sevilla María Francisca , Fernández-Villa Tania , Honrado Emiliano , Davila-Batista Veronica , Molina Antonio J.
Published: October 2017

Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis. The role of the gene EZH2 in colorectal cancer survival is uncertainly, the aim of this study is clear this relationship. Relevant literaure was searched from electronic databases. A meta-analysis was performed with elegible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with colorectal cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38–0.84) We performed bias analysis according Egger and Begg,s test and we did not find publication bias. EZH2 overexpression indicates a better prognosis for colorectal cancer.
Region and species dependent mechanical properties of adolescent and young adult brain tissue
Authors: MacManus David B. , Pierrat Baptiste , Murphy Jeremiah G. , Gilchrist Michael D.
Published: October 2017

Traumatic brain injuries, the leading cause of death and disability in children and young adults, are the result of a rapid acceleration or impact of the head. In recent years, a global effort to better understand the biomechanics of TBI has been undertaken, with many laboratories creating detailed computational models of the head and brain. For these models to produce realistic results they require accurate regional constitutive data for brain tissue. However, there are large differences in the mechanical properties reported in the literature. These differences are likely due to experimental parameters such as specimen age, brain region, species, test protocols, and fiber direction which are often not reported. Furthermore, there is a dearth of reported viscoelastic properties for brain tissue at large-strain and high rates. Mouse, rat, and pig brains are impacted at 10/s to a strain of ~36% using a custom-built micro-indenter with a 125 μm radius. It is shown that the resultant mechanical properties are dependent on specimen-age, species, and region, under identical experimental parameters.
Zero-dc-field rotation-direction-dependent magnetization switching induced by a circularly polarized microwave magnetic field
Authors: Suto Hirofumi , Kanao Taro , Nagasawa Tazumi , Mizushima Koichi , Sato Rie
Published: October 2017

Magnetization switching of high-anisotropy nanomagnets by a small magnetic field is a key challenge in developing future magnetic nanodevices. In this paper, we experimentally demonstrate magnetization switching of a perpendicularly magnetized nanomagnet induced solely by an in-plane circularly polarized microwave magnetic field. Applying a microwave field with an amplitude below 5% of the anisotropy field induces large ferromagnetic resonance excitation, which results in magnetization switching even in the absence of a dc field. This kind of magnetization switching is induced by a microwave field with a duration of 0.5 ns and is clearly dependent on the rotation direction of the microwave field.
Precision of a new ocular biometer in eyes with cataract using swept source optical coherence tomography combined with Placido-disk corneal topography
Authors: Wang Wenwen , Miao Yaxin , Savini Giacomo , McAlinden Colm , Chen Hao , Hu Qingjie , Wang Qinmei , Huang Jinhai
Published: October 2017

The present study was to assess the precision (repeatability and reproducibility) of a new optical biometer (OA-2000, Tomey, Japan) based on swept-source optical coherence tomography (SS-OCT) and Placido disk topography in eyes with cataracts. Seventy-eight eyes from seventy-eight patients with cataracts were evaluated. Axial length (AL), anterior chamber depth (ACD), keratometry (K) over a 2.5 mm and 3.0 mm diameter, lens thickness (LT), central corneal thickness (CCT) and white-to-white (WTW) distance were measured by 2 skilled operators. OA-2000 measurements were highly repeatable and reproducible for all parameters (intraclass correlation, 0.925 to 1.000). OA-2000 derived K-values with a diameter of 3.0mm showed narrower 95% limits of agreement (LoA) (SRK/T: −0.18 to 0.16D; Holladay 1: −0.20 to 0.19D; Hoffer Q: −0.22 to 0.20D) than those with a diameter of 2.5 mm for IOL power calculations (SRK/T: −0.20 to 0.20D; Holladay 1: −0.23 to 0.23D; Hoffer Q: −0.25 to 0.25D). The precision (repeatability and reproducibility) of the OA-2000 was excellent for all parameters. The 3.0mm diameter K-readings appear to be the most reliable choice for calculation of IOL power with the OA-2000. In addition, the average values determined from each operator’s 3 consecutive readings were more reproducible.
Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc region on its interaction with Fcγ receptor IIIa
Authors: Sakae Yoshitake , Satoh Tadashi , Yagi Hirokazu , Yanaka Saeko , Yamaguchi Takumi , Isoda Yuya , Iida Shigeru , Okamoto Yuko , Kato Koichi
Published: October 2017

Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction between the Fc region of immunoglobulin G1 (IgG1) and Fcγ receptor IIIa (FcγRIIIa), depending on N-glycosylation of these glycoproteins. In particular, core fucosylation of IgG1-Fc N-glycans negatively affects this interaction and thereby compromises ADCC activity. To address the mechanisms of this effect, we performed replica-exchange molecular dynamics simulations based on crystallographic analysis of a soluble form of FcγRIIIa (sFcγRIIIa) in complex with IgG1-Fc. Our simulation highlights increased conformational fluctuation of the N-glycan at Asn162 of sFcγRIIIa upon fucosylation of IgG1-Fc, consistent with crystallographic data giving no interpretable electron density for this N-glycan, except for the innermost part. The fucose residue disrupts optimum intermolecular carbohydrate-carbohydrate interactions, rendering this sFcγRIIIa glycan distal from the Fc glycan. Moreover, our simulation demonstrates that core fucosylation of IgG1-Fc affects conformational dynamics and rearrangements of surrounding amino acid residues, typified by Tyr296 of IgG1-Fc, which was more extensively involved in the interaction with sFcγRIIIa without Fc core fucosylation. Our findings offer a structural foundation for designing and developing therapeutic antibodies with improved ADCC activity.
Differential effects of speech situations on mothers’ and fathers’ infant-directed and dog-directed speech: An acoustic analysis
Authors: Gergely Anna , Faragó Tamás , Galambos Ágoston , Topál József
Published: October 2017

There is growing evidence that dog-directed and infant-directed speech have similar acoustic characteristics, like high overall pitch, wide pitch range, and attention-getting devices. However, it is still unclear whether dog- and infant-directed speech have gender or context-dependent acoustic features. In the present study, we collected comparable infant-, dog-, and adult directed speech samples (IDS, DDS, and ADS) in four different speech situations (Storytelling, Task solving, Teaching, and Fixed sentences situations); we obtained the samples from parents whose infants were younger than 30 months of age and also had pet dog at home. We found that ADS was different from IDS and DDS, independently of the speakers’ gender and the given situation. Higher overall pitch in DDS than in IDS during free situations was also found. Our results show that both parents hyperarticulate their vowels when talking to children but not when addressing dogs: this result is consistent with the goal of hyperspeech in language tutoring. Mothers, however, exaggerate their vowels for their infants under 18 months more than fathers do. Our findings suggest that IDS and DDS have context-dependent features and support the notion that people adapt their prosodic features to the acoustic preferences and emotional needs of their audience.
Increased HSP27 correlates with malignant biological behavior of non-small cell lung cancer and predicts patient’s survival
Authors: Sheng Baowei , Qi Congcong , Liu Bing , Lin Yong , Fu Tian , Zeng Qingdi
Published: October 2017

Heat shock protein 27 (HSP27) has been found to be related to tumorigenesis. The aim of this study was to investigate the expression pattern and clinical significance of HSP27 in non-small-cell lung cancer (NSCLC). The expression of HSP27 in tissues was examined by immunohistochemistry and serum level of HSP27 mRNA was detected by real-time PCR. The survival analysis was performed by a Kaplan Meier method and the estimation of risk factors was determined by the multiple regression analysis. The expression of HSP27 was increased in lung cancer tissues (p < 0.001) and serum (p < 0.001) of NSCLC patients and higher HSP27 in lung cancer tissues and serum of NSCLC patients was associated with poorly differentiated cancer (p < 0.001; p = 0.035), lymphatic metastasis (p < 0.001; p < 0.001), advanced TNM stage (p < 0.001; p < 0.001). And the levels of HSP27 in tissues and serum of lung cancer patients had a certain positive correlation (p = 0.046). Moreover, increased HSP27 expression correlated with shorter survival of NSCLC patients (p < 0.001). The results suggest that HSP27 may serve as a potential biomarker for diagnosis and prognosis of NSCLC.
Phenotypic Innovation and Adaptive Constraints in the Evolutionary Radiation of Palaeozoic Crinoids
Authors: Wright David F.
Published: October 2017

To better understand the patterns and processes shaping large-scale phenotypic diversification, I integrate palaeobiological and phylogenetic perspectives to investigate a ~200-million-year radiation using a global sample of Palaeozoic crinoid echinoderms. Results indicate the early history of crinoid diversification is characterized by early burst dynamics with decelerating morphologic rates. However, in contrast with expectation for a single “early burst” model, morphospace continued to expand following a slowdown in rates. In addition, I find evidence for an isolated peak in morphologic rates occurring late in the clade’s history. This episode of elevated rates is not associated with increased disparity, morphologic novelty, or the radiation of a single subclade. Instead, this episode of elevated rates involved multiple subclade radiations driven by environmental change toward a pre-existing adaptive optimum. The decoupling of morphologic disparity with rates of change suggests phenotypic rates are primarily shaped by ecologic factors rather than the origination of morphologic novelty alone. These results suggest phenotypic diversification is far more complex than models commonly assumed in comparative biology. Furthermore, palaeontological disparity patterns are not a reliable proxy for rates after an initial diversifying phase. These issues highlight the need for continued synthesis between fossil and phylogenetic approaches to macroevolution.
Health impact of E-cigarettes: a prospective 3.5-year study of regular daily users who have never smoked
Authors: Polosa Riccardo , Cibella Fabio , Caponnetto Pasquale , Maglia Marilena , Prosperini Umberto , Russo Cristina , Tashkin Donald
Published: October 2017

Although electronic cigarettes (ECs) are a much less harmful alternative to tobacco cigarettes, there is concern as to whether long-term ECs use may cause risks to human health. We report health outcomes (blood pressure, heart rate, body weight, lung function, respiratory symptoms, exhaled breath nitric oxide [eNO], exhaled carbon monoxide [eCO], and high-resolution computed tomography [HRCT] of the lungs) from a prospective 3.5-year observational study of a cohort of nine daily EC users (mean age 29.7 (±6.1) years) who have never smoked and a reference group of twelve never smokers. No significant changes could be detected over the observation period from baseline in the EC users or between EC users and control subjects in any of the health outcomes investigated. Moreover, no pathological findings could be identified on HRCT of the lungs and no respiratory symptoms were consistently reported in the EC user group. Although it cannot be excluded that some harm may occur at later stages, this study did not demonstrate any health concerns associated with long-term use of EC in relatively young users who did not also smoke tobacco.
The space of genotypes is a network of networks: implications for evolutionary and extinction dynamics
Authors: Yubero Pablo , Manrubia Susanna , Aguirre Jacobo
Published: October 2017

The forcing that environmental variation exerts on populations causes continuous changes with only two possible evolutionary outcomes: adaptation or extinction. Here we address this topic by studying the transient dynamics of populations on complex fitness landscapes. There are three important features of realistic landscapes of relevance in the evolutionary process: fitness landscapes are rough but correlated, their fitness values depend on the current environment, and many (often most) genotypes do not yield viable phenotypes. We capture these properties by defining time-varying, holey, NK fitness landscapes. We show that the structure of the space of genotypes so generated is that of a network of networks: in a sufficiently holey landscape, populations are temporarily stuck in local networks of genotypes. Sudden jumps to neighbouring networks through narrow adaptive pathways (connector links) are possible, though strong enough local trapping may also cause decays in population growth and eventual extinction. A combination of analytical and numerical techniques to characterize complex networks and population dynamics on such networks permits to derive several quantitative relationships between the topology of the space of genotypes and the fate of evolving populations.
A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit
Authors: Kopinja Johnny , Sevilla Raquel S. , Levitan Diane , Dai David , Vanko Amy , Spooner Edward , Ware Chris , Forget Robert , Hu Kun , Kral Astrid , Spacciapoli Peter , Kennan Richard , Jayaraman Lata , Pucci Vincenzo , Perera Samanthi , Zhang Weisheng , Fischer Christian , Lam Michael H.
Published: October 2017

Mutations in IDH1 are highly prevalent in human glioma. First line treatment is radiotherapy, which many patients often forego to avoid treatment-associated morbidities. The high prevalence of IDH1 mutations in glioma highlights the need for brain-penetrant IDH1 mutant-selective inhibitors as an alternative therapeutic option. Here, we have explored the utility of such an inhibitor in IDH1 mutant patient-derived models to assess the potential therapeutic benefits associated with intracranial 2-HG inhibition. Treatment of mutant IDH1 cell line models led to a decrease in intracellular 2-HG levels both in vitro and in vivo. Interestingly, inhibition of 2-HG production had no effect on in vitro IDH1 mutant glioma cell proliferation. In contrast, IDH1 mutant-selective inhibitors provided considerable survival benefit in vivo. However, even with near complete inhibition of intratumoral 2-HG production, not all mutant glioma models responded to treatment. The results suggest that disruption of 2-HG production with brain-penetrant inhibitors in IDH1 mutant gliomas may have substantial patient benefit.
CCN3 is a therapeutic target relating enhanced stemness and coagulation in hepatocellular carcinoma
Authors: Jia Qingan , Xue Tongchun , Zhang Qiangbo , Cheng Wei , Zhang Chun , Ma Jingwei , Bu Yang , Yu Songning , Liu Qingguang
Published: October 2017

The general prognosis of patients with hepatocellular carcinoma (HCC) remains extremely dismal, due to the high frequency of metastasis. Since 2003, our research group has explored the gene expression profiles of metastasized HCC tissue samples and identified a significant upregulation of CCN3. However, the role and precise pathological function of CCN3 remains elusive. We showed that CCN3 is associated with the poor prognosis of patients with HCC, the malignant phenotype of HCC, and vascular thrombosis. We further evaluated the negative roles of CCN3 in vitro and in vivo, and identified osteopontin (OPN), and coagulation factors tissue factor (TF) and thrombin as the leading genes downstream of CCN3, that are positively associated with HCC cell stemness. We demonstrated that overexpressed CCN3 in HCC cells leads to enhanced survival and increased number of pulmonary metastases in vivo. The elevated levels of OPN and TF were associated with signal activation of nuclear factor κB (NFκB) and extracellular signal-regulated kinases (ERK). Our findings suggest CCN3 is a potential therapeutic target that would affect the upregulation of OPN and coagulation factors, which would lead to an enhanced stemness and blood coagulation microenvironment in HCC tissue.
Combined TDDFT and AIM Insights into Photoinduced Excited State Intramolecular Proton Transfer (ESIPT) Mechanism in Hydroxyl- and Amino-Anthraquinone Solution
Authors: Zheng Daoyuan , Zhang Mingzhen , Zhao Guangjiu
Published: October 2017

Time-dependent density functional theory (TDDFT) and atoms in molecules (AIM) theory are combined to study the photoinduced excited state intramolecular proton transfer (ESIPT) dynamics for eight anthraquinones (AQs) derivatives in solution. The calculated absorption and emission spectra are consistent with the available experimental data, verifying the suitability of the theory selected. The systems with the excited-state exothermic proton transfer, such as 1-HAQ, 1,5-DHAQ and TFAQ, emit completely from transfer structure (T), while the reactions for those without ESIPT including 1,4-DHAQ and AAAQ appear to be endothermic. Three reaction properties of three systems (1,8-DHAQ, DCAQ and CAAQ) are between the exothermic and endothermic, sensitive to the solvent. Energy scanning shows that 1,4-DHAQ and AAAQ exhibit the higher ESIPT energy barriers compared to 1-HAQ, 1,5-DHAQ and TFAQ with the “barrierless” ESIPT process. The ESIPT process is facilitated by the strengthening of hydrogen bonds in excited state. With AIM theory, it is observed that the change in electrons density ρ(r) and potential energy density V(r) at BCP position between ground state and excited state are crucial factors to quantitatively elucidate the ESIPT.
A single extracellular amino acid in Free Fatty Acid Receptor 2 defines antagonist species selectivity and G protein selection bias
Authors: Sergeev Eugenia , Hansen Anders Højgaard , Bolognini Daniele , Kawakami Kouki , Kishi Takayuki , Aoki Junken , Ulven Trond , Inoue Asuka , Hudson Brian D. , Milligan Graeme
Published: October 2017

Free Fatty Acid Receptor 2 is a GPCR activated by short chain fatty acids produced in high levels in the lower gut by microbial fermentation of non-digestible carbohydrates. A major challenge in studying this receptor is that the mouse ortholog does not have significant affinity for antagonists that are able to block the human receptor. Docking of exemplar antagonists from two chemical series to homology models of both human and mouse Free Fatty Acid Receptor 2 suggested that a single lysine - arginine variation at the extracellular face of the receptor might provide the basis for antagonist selectivity and mutational swap studies confirmed this hypothesis. Extending these studies to agonist function indicated that although the lysine - arginine variation between human and mouse orthologs had limited effect on G protein-mediated signal transduction, removal of positive charge from this residue produced a signalling-biased variant of Free Fatty Acid Receptor 2 in which Gi-mediated signalling by both short chain fatty acids and synthetic agonists was maintained whilst there was marked loss of agonist potency for signalling via Gq/11 and G12/13 G proteins. A single residue at the extracellular face of the receptor thus plays key roles in both agonist and antagonist function.
Ionic liquid-based dispersive liquid-liquid microextraction combined with functionalized magnetic nanoparticle solid-phase extraction for determination of industrial dyes in water
Authors: Liang Ning , Hou Xiaohong , Huang Peiting , Jiang Chao , Chen Lijuan , Zhao Longshan
Published: October 2017

N-butyl pyridinium bis((trifluoromethyl)sulfonyl)imide ([Hpy]NTf2) functionalized core/shell magnetic nanoparticles (MNPs, Fe3O4@SiO2@[Hpy]NTf2)) were prepared and applied as an adsorbent for magnetic solid phase extraction (MSPE) of three commonly used industrial dyes including malachite green, crystal violet and methylene blue. Extraction solution was mixed with 100 mg extraction material of Fe3O4@SiO2@[Hpy]NTf2, and 1 mL of acetonitrile was used to elute target analytes for further extraction and purification. [Hpy]NTf2 was used as extraction solution, and 500 μL methanol was selected as dispersive solvent in ionic liquid (IL) dispersive liquid–liquid microextraction (DLLME) method. After sonication for 5 min and centrifugation at 447 g for 10 min, 20 μL of sedimented phase was injected into HPLC-UV system. The limit of detection (LOD) and limit of quantification (LOQ) of current method were 0.03 and 0.16 μg·L−1, respectively, which indicated the sensitivity was comparable or even superior to other reported methods. The relative recoveries of the target analytes ranged from 86.1% to 100.3% with relative standard deviations between 0.3% and 4.5%. The developed method has been successfully applied to determine the level of three industrial dyes in different water samples.
Maternal Glucocorticoid Elevation and Associated Fetal Thymocyte Apoptosis are Involved in Immune Disorders of Prenatal Caffeine Exposed Offspring Mice
Authors: Liu Han-xiao , Chen Ting , Wen Xiao , Qu Wen , Liu Sha , Yan Hui-yi , Hou Li-fang , Ping Jie
Published: October 2017

Our previous study showed that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) and glucocorticoid elevation in the fetus. Researchers suggested that IUGR is a risk factor for T helper cell (Th)1/Th2 deviation. However, whether PCE can induce these immune disorders and the underlying mechanisms of that induction remain unknown. This study aimed to observe the effects of PCE on the Th1/Th2 balance in offspring and further explore the developmental origin mechanisms from the perspective of glucocorticoid overexposure-induced thymocyte apoptosis. An IUGR model was established by caffeine administration from gestational day (GD) 9 to GD 18, and the offspring were immunized on postnatal day (PND) 42. The results show that maternal glucocorticoid overexposure increased fetal thymocyte apoptosis by activating both the Fas-mediated and the Bim-regulated apoptotic pathways. After birth, accelerated thymocyte apoptosis and Th1 suppression were also found in the PCE offspring at PND 14 and PND 49. Moreover, the PCE offspring showed immune disorders after immunization, manifesting as increased IgG1/IgG2a ratio and IL-4 production in the serum. In conclusion, PCE could induce fetal overexposure to maternal glucocorticoids and increase thymocyte apoptosis, which could persist into postnatal life and be implicated in Th1 inhibition and further immune disorders.
The Subpolar North Atlantic Ocean Heat Content Variability and its Decomposition
Authors: Zhang Weiwei , Yan Xiao-Hai
Published: October 2017

The Subpolar North Atlantic (SPNA) is one of the most important areas to global climate because its ocean heat content (OHC) is highly correlated with the Atlantic Meridional Overturning Circulation (AMOC), and its circulation strength affects the salt transport by the AMOC, which in turn feeds and sustains the strength of the AMOC. Moreover, the recent global surface warming “hiatus” may be attributed to the SPNA as one of the major planetary heat sinks. Although almost synchronized before 1996, the OHC has greater spatial disparities afterwards, which cannot be explained as driven by the North Atlantic Oscillation (NAO). Temperature decomposition reveals that the western SPNA OHC is mainly determined by the along isopycnal changes, while in the eastern SPNA along isopycnal changes and isopycnal undulation are both important. Further analysis indicates that heat flux dominates the western SPNA OHC, but in the eastern SPNA wind forcing affects the OHC significantly. It is worth noting that the along isopycnal OHC changes can also induce heaving, thus the observed heaving domination in global oceans cannot mask the extra heat in the ocean during the recent “hiatus”.
Microsphere Assisted Super-resolution Optical Imaging of Plasmonic Interaction between Gold Nanoparticles
Authors: Hou Beibei , Xie Mengran , He Ruoyu , Ji Minbiao , Trummer Sonja , Fink Rainer H. , Zhang Luning
Published: October 2017

Conventional far-field microscopy cannot directly resolve the sub-diffraction spatial distribution of localized surface plasmons in metal nanostructures. Using BaTiO3 microspheres as far-field superlenses by collecting the near-field signal, we can map the origin of enhanced two-photon photoluminescence signal from the gap region of gold nanosphere dimers and gold nanorod dimers beyond the diffraction limit, on a conventional far-field microscope. As the angle θ between dimer’s structural axis and laser polarisation changes, photoluminescence intensity varies with a cos4θ function, which agrees quantitatively with numerical simulations. An optical resolution of about λ/7 (λ: two-photon luminescence central wavelength) is demonstrated at dimer’s gap region.
Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and Smokers for Representing Potential Therapeutic Targets
Authors: Pazhouhandeh Mehrdad , Samiee Fatemeh , Boniadi Tahereh , Khedmat Abbas Fadaei , Vahedi Ensieh , Mirdamadi Mahsa , Sigari Naseh , Siadat Seyed Davar , Vaziri Farzam , Fateh Abolfazl , Ajorloo Faezeh , Tafsiri Elham , Ghanei Mostafa , Mahboudi Fereidoun , Rahimi Jamnani Fatemeh
Published: October 2017

Cigarette smoking is the leading cause of lung cancer worldwide. In this study, we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung cancer (NSCLC) patients and smokers (SM), leading to the identification of overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface- and solution-phase biopanning were performed on immunoglobulin G purified from the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides were detected, which were used to generate NSCLC and SM protein datasets. NSCLC- and SM-related proteins were visualized using STRING and Gephi, and their modules were analyzed using Enrichr. By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation. Taken together, assessment of the AAb repertoires using a systems biology approach can delineate the hidden events involved in various disorders.
Graphene oxide electrodeposited electrode enhances start-up and selective enrichment of exoelectrogens in bioelectrochemical systems
Authors: Alonso R. M. , San-Martín M. I. , Sotres A. , Escapa A.
Published: October 2017

This study seeks to assess the impact that the anodic electrodeposition of graphene oxide (GO) has on the start-up process and on the development of microbial communities on the anode of BESs. The GO electrodeposited electrodes were characterised in abiotic conditions to verify the extent of the modification and were then transferred to a bioelectrochemical reactor. Results showed that the modified electrode allowed for a reduced start-up time compared to the control electrode. After three months, high throughput sequencing was performed, revealing that electrochemically reduced graphene oxide acts as a selective agent toward exoelectrogenic bacteria as Geobacter. Overall, this study shows that GO modified electrodes enhance biofilm build up in BES.
Improved emission of SiV diamond color centers embedded into concave plasmonic core-shell nanoresonators
Authors: Szenes András , Bánhelyi Balázs , Szabó Lóránt Zs. , Szabó Gábor , Csendes Tibor , Csete Mária
Published: October 2017

Configuration of three different concave silver core-shell nanoresonators was numerically optimized to enhance the excitation and emission of embedded silicon vacancy (SiV) diamond color centers simultaneously. Conditional optimization was performed to ensure ~20–30–40 and 50% apparent quantum efficiency (cQE) of SiV color centers. The enhancement spectra, as well as the near-field and charge distribution were inspected to uncover the underlying nanophotonical phenomena. The conditionally optimized coupled systems were qualified by the product of the radiative rate enhancements at the excitation and emission, which is nominated as Px factor. The optimized spherical core-shell nanoresonator containing a centralized emitter is capable of enhancing the emission considerably via bonding dipolar resonance. The Px factor is 529-fold with 49.7% cQE at the emission. Decentralization of the emitter leads to appearance of higher order nonradiative multipolar modes. Transversal and longitudinal dipolar resonance of the optimized ellipsoidal core-shell resonator was tuned to the excitation and emission, which results in 6.2∙105Px factor with 50.6% cQE at the emission. Rod-shaped concave core-shell nanoresonators exploit similar transversal and longitudinal dipolar resonance, moreover they enhance the fluorescence more significantly due to their antenna-like geometry. Px factor indicating 8.34∙105 enhancement is achievable while the cQE is 50.3% at the emission.
Endogenous physical regulation of population density in the freshwater protozoan Paramecium caudatum
Authors: Fels Daniel
Published: October 2017

Studies confirm physical long-range cell-cell communication, most evidently based on electromagnetic fields. Effects concern induction or inhibition of cell growth. Their natural function is unclear. With the protozoan Paramecium caudatum I tested whether the signals regulate cell density and are electromagnetic. Up to 300 cells/mL, cell growth in clones of this study is decreasingly pronounced. Using cuvettes as chemical barriers enabling physical communication  I  placed 5 indicator cells/mL, the inducer populations, into smaller cuvettes that stand in bigger and contained 50, 100, 200 or 300 cells/mL. Under conditions of total darkness such pairs were mutually exposed for 48 hours. The hypothesis was that indicator cells, too, grow less the more neighbor cells there are. The bigger inducer populations were in the beginning the less they grew. The indicator populations grew accordingly; the more cells they were surrounded by the less they grew. The suppressing neighbors-effect disappeared when inner cuvettes were shielded by graphite known to shield electromagnetic radiation from GHz to PHz, i.e. to absorb energy from microwaves to light. These are the first results demonstrating non-contact physical quorum sensing for cell population density regulation. I assume rules intrinsic to electromagnetic fields interacting with matter and life.
Gene expression atlas of fruit ripening and transcriptome assembly from RNA-seq data in octoploid strawberry (Fragaria × ananassa)
Authors: Sánchez-Sevilla José F. , Vallarino José G. , Osorio Sonia , Bombarely Aureliano , Posé David , Merchante Catharina , Botella Miguel A. , Amaya Iraida , Valpuesta Victoriano
Published: October 2017

RNA-seq has been used to perform global expression analysis of the achene and the receptacle at four stages of fruit ripening, and of the roots and leaves of strawberry (Fragaria × ananassa). About 967 million reads and 191 Gb of sequence were produced, using Illumina sequencing. Mapping the reads in the related genome of the wild diploid Fragaria vesca revealed differences between the achene and receptacle development program, and reinforced the role played by ethylene in the ripening receptacle. For the strawberry transcriptome assembly, a de novo strategy was followed, generating separate assemblies for each of the ten tissues and stages sampled. The Trinity program was used for these assemblies, resulting in over 1.4 M isoforms. Filtering by a threshold of 0.3 FPKM, and doing Blastx (E-value < 1 e-30) against the UniProt database of plants reduced the number to 472,476 isoforms. Their assembly with the MIRA program (90% homology) resulted in 26,087 contigs. From these, 91.34 percent showed high homology to Fragaria vesca genes and 87.30 percent Fragaria iinumae (BlastN E-value < 1 e-100). Mapping back the reads on the MIRA contigs identified polymorphisms at nucleotide level, using FREEBAYES, as well as estimate their relative abundance in each sample.
Enhanced Cell Adhesion on a Nano-Embossed, Sticky Surface Prepared by the Printing of a DOPA-Bolaamphiphile Assembly Ink
Authors: Lee Chaemyeong , Kim Seung-Hyun , Jang Jae-Hyung , Lee Sang-Yup
Published: October 2017

Inspired by adhesive mussel proteins, nanospherical self-assemblies were prepared from bolaamphiphiles containing 3,4-dihydroxyphenylalanine (DOPA) moieties, and a suspension of the bolaamphiphile assemblies was used for the preparation of a patterned surface that enhanced cell adhesion and viability. The abundant surface-exposed catechol groups on the robust bolaamphiphile self-assemblies were responsible for their outstanding adhesivity to various surfaces and showed purely elastic mechanical behaviour in response to tensile stress. Compared to other polydopamine coatings, the spherical DOPA-bolaamphiphile assemblies were coated uniformly and densely on the surface, yielding a nano-embossed surface. Cell culture tests on the surface modified by DOPA-bolaamphiphiles also showed enhanced cellular adhesivity and increased viability compared to surfaces decorated with other catecholic compounds. Furthermore, the guided growth of a cell line was demonstrated on the patterned surface, which was prepared by inkjet printing using a suspension of the self-assembled particles as an ink. The self-assembly of DOPA-bolaamphiphiles shows that they are a promising adhesive, biocompatible material with the potential to modify various substances.
DDX3 regulates endoplasmic reticulum stress-induced ATF4 expression
Authors: Adjibade Pauline , Grenier St-Sauveur Valérie , Bergeman Jonathan , Huot Marc-Etienne , Khandjian Edouard W. , Mazroui Rachid
Published: October 2017

Accumulation of unfolded and potentially toxic proteins in the endoplasmic reticulum (ER) activates a cell stress adaptive response, which involves a reprogramming of general gene expression. ATF4 is a master stress-induced transcription factor that orchestrates gene expression in cells treated with various ER stress inducers including those used to treat cancers. ER stress-induced ATF4 expression occurs mainly at the translational level involving the activity of the phosphorylated (P) translation initiation factor (eIF) eIF2α. While it is well established that under ER stress PeIF2α drives ATF4 expression through a specialised mode of translation re-initiation, factors (e.g. RNA-binding proteins and specific eIFs) involved in PeIF2α-mediated ATF4 translation remain unknown. Here we identified the RNA-binding protein named DDX3 as a promotor of ATF4 expression in cancer cells treated with sorafenib, an ER stress inducer used as a chemotherapeutic. Depletion experiments showed that DDX3 is required for PeIF2α-mediated ATF4 expression. Luciferase and polyribosomes assays showed that DDX3 drives ER stress-induced ATF4 mRNA expression at the translational level. Protein-interaction assays showed that DDX3 binds the eIF4F complex, which we found to be required for ER stress-induced ATF4 expression. This study thus showed that PeIF2α-mediated ATF4 mRNA translation requires DDX3 as a part of the eIF4F complex.
Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y1 Receptor
Authors: Li Yang , Yin Can , Liu Pi , Li Dongmei , Lin Jianping
Published: October 2017

The human P2Y1 receptor (P2Y1R) is a purinergic G-protein-coupled receptor (GPCR) that functions as a receptor for adenosine 5′-diphosphate (ADP). An antagonist of P2Y1R might potentially have antithrombotic effects, whereas agonists might serve as antidiabetic agents. On the basis of the antagonist-bound MRS2500-P2Y1R crystal structure, we constructed computational models of apo-P2Y1R and the agonist-receptor complex 2MeSADP-P2Y1R. We then performed conventional molecular dynamics (cMD) and accelerated molecular dynamics (aMD) simulations to study the conformational dynamics after binding with agonist/antagonist as well as the P2Y1R activation mechanism. We identified a new agonist-binding site of P2Y1R that is consistent with previous mutagenesis data. This new site is deeper than those of the agonist ADP in the recently simulated ADP-P2Y1R structure and the antagonist MRS2500 in the MRS2500-P2Y1R crystal structure. During P2Y1R activation, the cytoplasmic end of helix VI shifts outward 9.1 Å, the Ser1463.47-Tyr2375.58 hydrogen bond breaks, a Tyr2375.58-Val2626.37 hydrogen bond forms, and the conformation of the χ1 rotamer of Phe2696.44 changes from parallel to perpendicular to helix VI. The apo-P2Y1R system and the MRS2500-P2Y1R system remain inactive. The newly identified agonist binding site and activation mechanism revealed in this study may aid in the design of P2Y1R antagonists/agonists as antithrombotic/antidiabetic agents, respectively.
Computer-aided evaluation of the correlation between MRI morphology and immunohistochemical biomarkers or molecular subtypes in breast cancer
Authors: Jiang Sen , Hong You-Jia , Zhang Fan , Li Yang-Kang
Published: October 2017

Studies using tumor circularity (TC), a quantitative MRI morphologic index, to evaluate breast cancer are scarce. The purpose of this study is to evaluate the correlation between TC and immunohistochemical biomarkers or molecular subtypes in breast cancer. 146 patients with 150 breast cancers were selected. All tumors were confirmed by histopathology and examined by 3.0T MRI. TC was calculated by computer-aided software. The associations between TC and patient age, tumor size, histological grade, molecular subtypes, and immunohistochemical biomarkers including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed. TC correlated inversely with tumor size (r = −0.224, P < 0.001), ER (r = −0.490, P < 0.001) and PR (r = −0.484, P < 0.001). However, TC correlated positively with Ki67 (r = 0.332, P < 0.001) and histological grade (r = 0.309, P < 0.001). In multiple linear regression analysis, tumor size, ER, PR and Ki67 were independent influential factors of TC. Compared with HER2-overexpressed (61.6%), luminal A (54.7%) and luminal B (52.3%) subtypes, triple-negative breast cancer (TNBC) showed the highest score of TC (70.8%, P < 0.001). Our study suggests that TC can be used as an imaging biomarker to predict the aggressiveness of newly diagnosed breast cancers. TNBC seems to present as an orbicular appearance when comparing with other subtypes.
Localised genetic heterogeneity provides a novel mode of evolution in dsDNA phages
Authors: Magill Damian J. , Kucher Phillip A. , Krylov Victor N. , Pleteneva Elena A. , Quinn John P. , Kulakov Leonid A.
Published: October 2017

The Red Queen hypothesis posits that antagonistic co-evolution between interacting species results in recurrent natural selection via constant cycles of adaptation and counter-adaptation. Interactions such as these are at their most profound in host-parasite systems, with bacteria and their viruses providing the most intense of battlefields. Studies of bacteriophage evolution thus provide unparalleled insight into the remarkable elasticity of living entities. Here, we report a novel phenomenon underpinning the evolutionary trajectory of a group of dsDNA bacteriophages known as the phiKMVviruses. Employing deep next generation sequencing (NGS) analysis of nucleotide polymorphisms we discovered that this group of viruses generates enhanced intraspecies heterogeneity in their genomes. Our results show the localisation of variants to genes implicated in adsorption processes, as well as variation of the frequency and distribution of SNPs within and between members of the phiKMVviruses. We link error-prone DNA polymerase activity to the generation of variants. Critically, we show trans-activity of this phenomenon (the ability of a phiKMVvirus to dramatically increase genetic variability of a co-infecting phage), highlighting the potential of phages exhibiting such capabilities to influence the evolutionary path of other viruses on a global scale.
11β-hydroxysteroid dehydrogenase type 1 has no effect on survival during experimental malaria but affects parasitemia in a parasite strain-specific manner
Authors: Vandermosten L. , De Geest C. , Knoops S. , Thijs G. , Chapman K. E. , De Bosscher K. , Opdenakker G. , Van den Steen P. E.
Published: October 2017

Malaria is a global disease associated with considerable mortality and morbidity. An appropriately balanced immune response is crucial in determining the outcome of malarial infection. The glucocorticoid (GC) metabolising enzyme, 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) converts intrinsically inert GCs into active GCs. 11β-HSD1 shapes endogenous GC action and is immunomodulatory. We investigated the role of 11β-HSD1 in two mouse models of malaria. 11β-HSD1 deficiency did not affect survival after malaria infection, but it increased disease severity and parasitemia in mice infected with Plasmodium chabaudi AS. In contrast, 11β-HSD1 deficiency rather decreased parasitemia in mice infected with the reticulocyte-restricted parasite Plasmodium berghei NK65 1556Cl1. Malaria-induced antibody production and pathology were unaltered by 11β-HSD1 deficiency though plasma levels of IL-4, IL-6 and TNF-α were slightly affected by 11β-HSD1 deficiency, dependent on the infecting parasite. These data suggest that 11β-HSD1 is not crucial for survival of experimental malaria, but alters its progression in a parasite strain-specific manner.
Alpha-1 antitrypsin augmentation therapy decreases miR-199a-5p, miR-598 and miR-320a expression in monocytes via inhibition of NFκB
Authors: Hassan Tidi , de Santi Chiara , Mooney Catherine , McElvaney Noel G. , Greene Catherine M.
Published: October 2017

Alpha-1 antitrypsin (AAT) augmentation therapy involves infusion of plasma-purified AAT to AAT deficient individuals. Whether treatment affects microRNA expression has not been investigated. This study’s objectives were to evaluate the effect of AAT augmentation therapy on altered miRNA expression in monocytes and investigate the mechanism. Monocytes were isolated from non-AAT deficient (MM) and AAT deficient (ZZ) individuals, and ZZs receiving AAT. mRNA (qRT-PCR, microarray), miRNA (miRNA profiling, qRT-PCR), and protein (western blotting) analyses were performed. Twenty one miRNAs were differentially expressed 3-fold between ZZs and MMs. miRNA validation studies demonstrated that in ZZ monocytes receiving AAT levels of miR-199a-5p, miR-598 and miR-320a, which are predicted to be regulated by NFκB, were restored to levels similar to MMs. Validated targets co-regulated by these miRNAs were reciprocally increased in ZZs receiving AAT in vivo and in vitro. Expression of these miRNAs could be increased in ZZ monocytes treated ex vivo with an NFκB agonist and decreased by NFκB inhibition. p50 and p65 mRNA and protein were significantly lower in ZZs receiving AAT than untreated ZZs. AAT augmentation therapy inhibits NFκB and decreases miR-199a-5p, miR-598 and miR-320a in ZZ monocytes. These NFκB-inhibitory properties may contribute to the anti-inflammatory effects of AAT augmentation therapy.