bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical behaviour in the optimal generation of multipartite entanglement
Authors: Moreno M. G. M. , Parisio Fernando
Published: July 2017

Two systems whose correlations cannot be classically accounted for display the simplest instance of quantum entanglement. Although this two-party association has caused a revolution in the foundations and uses of quantum mechanics, genuine entanglement among several parties unveils a whole new class of phenomena and applications. In this work we suggest a way to prepare Dicke states from a tunable source of bipartite entanglement to investigate foundational issues. The scheme has the following distinctive features: (i) it relies on controlled information loss and unentangled measurements; (ii) irrespective of the source entanglement, whenever a Dicke state is produced, it is ideal; (iii) the optimal entanglement of the bipartite source undergoes a second-order-like transition depending on the parameters of the Dicke state to be produced. These properties lead to asymptotic results on the entanglement between any qubit belonging to a Dicke state and the remaining qubits.
RETRACTED ARTICLE: Fibulin-3 promotes osteosarcoma invasion and metastasis by inducing epithelial to mesenchymal transition and activating the Wnt/β-catenin signaling pathway
Authors: Wang Songgang , Zhang Dong , Han Shasha , Gao Peng , Liu Changying , Li Jianmin , Pan Xin
Published: July 2017

This study explored the role of fibulin-3 in osteosarcoma progression and the possible signaling pathway involved. Fibulin-3 mRNA and protein expression in normal tissue, benign fibrous dysplasia, osteosarcoma, osteosarcoma cell lines (HOS and U-2OS), the normal osteoblastic cell line hFOB, and different invasive subclones was evaluated by immunohistochemistry (IHC) or immunocytochemistry (ICC) and real time reverse transcriptase-polymerase chain reaction (real time qRT-PCR). To assess the role of fibulin-3 in the invasion and metastasis of osteosarcoma cells, lentiviral vectors with fibulin-3 small hairpin RNA (shRNA) and pLVX-fibulin-3 were constructed and used to infect the highly invasive and low invasive subclones. The effects of fibulin-3 knockdown and upregulation on the biological behavior of osteosarcoma cells were investigated by functional in vitro and in vivo assays. The results revealed that fibulin-3 expression was upregulated in osteosarcoma, and was positively correlated with low differentiation, lymph node metastasis, and poor prognosis. Fibulin-3 could promote osteosarcoma cell invasion and metastasis by inducing EMT and activating the Wnt/β-catenin signaling pathway. Collectively, our findings demonstrate that fibulin-3 is a promoter of osteosarcoma development and progression, and suggest a novel therapeutic target for future studies.
Ecologically relevant levels of multiple, common marine stressors suggest antagonistic effects
Authors: Lange Rolanda , Marshall Dustin
Published: July 2017

Stressors associated with global change will be experienced simultaneously and may act synergistically, so attempts to estimate the capacity of marine systems to cope with global change requires a multi-stressor approach. Because recent evidence suggests that stressor effects can be context-dependent, estimates of how stressors are experienced in ecologically realistic settings will be particularly valuable. To enhance our understanding of the interplay between environmental effects and the impact of multiple stressors from both natural and anthropogenic sources, we conducted a field experiment. We explored the impact of multiple, functionally varied stressors from both natural and anthropogenic sources experienced during early life history in a common sessile marine invertebrate,Bugula neritina. Natural spatial environmental variation induced differences in conspecific densities, allowing us to test for density-driven context-dependence of stressor effects. We indeed found density-dependent effects. Under high conspecific density, individual survival increased, which offset part of the negative effects of experiencing stressors. Experiencing multiple stressors early in life history translated to a decreased survival in the field, albeit the effects were not as drastic as we expected: our results are congruent with antagonistic stressor effects. We speculate that when individual stressors are more subtle, stressor synergies become less common.
Ab Initio Density Functional Calculations and Infra-Red Study of CO Interaction with Pd Atoms on θ-Al2O3 (010) Surface
Authors: Narula Chaitanya K. , Allard Lawrence F. , Wu Zili
Published: July 2017

The ab initio density functional theoretical studies show that energetics favor CO oxidation on single Pd atoms supported on θ-alumina. The diffuse reflectance infra-red spectroscopy (DRIFTS) results show that carbonates are formed as intermediates when single supported Pd atoms are exposed to a gaseous mixture of CO + O2. The rapid agglomeration of Pd atoms under CO oxidation conditions even at 6 °C leads to the presence of Pd particles along with single atoms during CO oxidation experiments. Thus, the observed CO oxidation has contributions from both single Pd atoms and Pd particles.
A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP
Authors: Zhu Yingmin , Mei Fang , Luo Pei , Cheng Xiaodong
Published: July 2017

Extensive functional studies of the exchange protein directly activated by cAMP (EPAC) family of signaling molecules have demonstrated that EPAC proteins play a fundamental role in several physiological and pathophysiological responses, therefore are attractive drug targets. In this report, the development of a cell-based, medium to high throughput screening assay that is capable of monitoring EPAC-mediated activation of cellular Rap1 in an isoform-specific manner is described. This assay adapts a conventional ELISA format with immobilized RalGDS-RBD as a bait to selectively capture GTP-bound active Rap1. As a result, it fills an urgent need for a cell-based EPAC assay that can be conveniently performed using microtiter plates for the discovery and/or validation of isoform-specific EPAC agonists and antagonists.
Phonon Conduction in Silicon Nanobeam Labyrinths
Authors: Park Woosung , Romano Giuseppe , Ahn Ethan C. , Kodama Takashi , Park Joonsuk , Barako Michael T. , Sohn Joon , Kim Soo Jin , Cho Jungwan , Marconnet Amy M. , Asheghi Mehdi , Kolpak Alexie M. , Goodson Kenneth E.
Published: July 2017

Here we study single-crystalline silicon nanobeams having 470 nm width and 80 nm thickness cross section, where we produce tortuous thermal paths (i.e. labyrinths) by introducing slits to control the impact of the unobstructed “line-of-sight” (LOS) between the heat source and heat sink. The labyrinths range from straight nanobeams with a complete LOS along the entire length to nanobeams in which the LOS ranges from partially to entirely blocked by introducing slits, s = 95, 195, 245, 295 and 395 nm. The measured thermal conductivity of the samples decreases monotonically from ~47 W m−1 K−1 for straight beam to ~31 W m−1 K−1 for slit width of 395 nm. A model prediction through a combination of the Boltzmann transport equation and ab initio calculations shows an excellent agreement with the experimental data to within ~8%. The model prediction for the most tortuous path (s = 395 nm) is reduced by ~14% compared to a straight beam of equivalent cross section. This study suggests that LOS is an important metric for characterizing and interpreting phonon propagation in nanostructures.
High Energy Radical Chemistry Formation of HCN-rich Atmospheres on early Earth
Authors: Ferus Martin , Kubelík Petr , Knížek Antonín , Pastorek Adam , Sutherland John , Civiš Svatopluk
Published: July 2017

Recent results in prebiotic chemistry implicate hydrogen cyanide (HCN) as the source of carbon and nitrogen for the synthesis of nucleotide, amino acid and lipid building blocks. HCN can be produced during impact events by reprocessing of carbonaceous and nitrogenous materials from both the impactor and the atmosphere; it can also be produced from these materials by electrical discharge. Here we investigate the effect of high energy events on a range of starting mixtures representative of various atmosphere-impactor volatile combinations. Using continuously scanning time–resolved spectrometry, we have detected ·CN radical and excited CO as the initially most abundant products. Cyano radicals and excited carbon monoxide molecules in particular are reactive, energy-rich species, but are resilient owing to favourable Franck–Condon factors. The subsequent reactions of these first formed excited species lead to the production of ground-state prebiotic building blocks, principally HCN.
Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer
Authors: Zhang Jun , Yao Tingting , Lin Zhongqiu , Gao Yali
Published: July 2017

Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients’ plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively. Moreover, the accuracy was good enough for MEG3 methylation in plasma to discriminate CIN III patients from healthy participants. In addition, MEG3 methylation in plasma also has high discriminating power to predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation of MEG3 in plasma was associated with worse recurrence-free and overall survival in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve as a diagnostic and prognostic biomarker for cervical cancer, providing useful information for clinical management.
Novel risk genes for systemic lupus erythematosus predicted by random forest classification
Authors: Almlöf Jonas Carlsson , Alexsson Andrei , Imgenberg-Kreuz Juliana , Sylwan Lina , Bäcklin Christofer , Leonard Dag , Nordmark Gunnel , Tandre Karolina , Eloranta Maija-Leena , Padyukov Leonid , Bengtsson Christine , Jönsen Andreas , Dahlqvist Solbritt Rantapää , Sjöwall Christopher , Bengtsson Anders A. , Gunnarsson Iva , Svenungsson Elisabet , Rönnblom Lars , Sandling Johanna K. , Syvänen Ann-Christine
Published: July 2017

Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual’s SLE risk we designed a random forest classifier using SNP genotype data generated on the “Immunochip” from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.
Human Zika infection induces a reduction of IFN-γ producing CD4 T-cells and a parallel expansion of effector Vδ2 T-cells
Authors: Cimini Eleonora , Castilletti Concetta , Sacchi Alessandra , Casetti Rita , Bordoni Veronica , Romanelli Antonella , Turchi Federica , Martini Federico , Tumino Nicola , Nicastri Emanuele , Corpolongo Angela , Di Caro Antonino , Kobinger Gary , Zumla Alimuddin , Capobianchi Maria Rosaria , Ippolito Giuseppe , Agrati Chiara
Published: July 2017

The definition of the immunological response to Zika (ZIKV) infection in humans represents a key issue to identify protective profile useful for vaccine development and for pathogenesis studies. No data are available on the cellular immune response in the acute phase of human ZIKV infection, and its role in the protection and/or pathogenesis needs to be clarified. We studied and compared the phenotype and functionality of T-cells in patients with acute ZIKV and Dengue viral (DENV) infections. A significant activation of T-cells was observed during both ZIKV and DENV infections. ZIKV infection was characterized by a CD4 T cell differentiation toward effector cells and by a lower frequency of IFN-γ producing CD4 T cells. Moreover, a substantial expansion of CD3+CD4−CD8− T-cell subset expressing Vδ2 TCR was specifically observed in ZIKV patients. Vδ2 T cells presented a terminally differentiated profile, expressed granzyme B and maintained their ability to produce IFN-γ. These findings provide new knowledge on the immune response profile during self-limited infection that may help in vaccine efficacy definition, and in identifying possible immuno-pathogenetic mechanisms of severe infection.
Digging up food: excavation stone tool use by wild capuchin monkeys
Authors: Falótico Tiago , Siqueira José O. , Ottoni Eduardo B.
Published: July 2017

Capuchin monkeys at Serra da Capivara National Park (SCNP) usually forage on the ground for roots and fossorial arthropods, digging primarily with their hands but also using stone tools to loosen the soil and aid the digging process. Here we describe the stone tools used for digging by two groups of capuchins on SCNP. Both groups used tools while digging three main food resources:Thiloa glaucocarpatubers,Ocoteasp roots, and trapdoor spiders. One explanation for the occurrence of tool use in primates is the “necessity hypothesis”, which states that the main function of tool use is to obtain fallback food. We tested for this, but only found a positive correlation between plant food availability and the frequency of stone tools’ use. Thus, our data do not support the fallback food hypothesis for the use of tools to access burrowed resources.
Demonstrating an absolute quantum advantage in direct absorption measurement
Authors: Moreau Paul-Antoine , Sabines-Chesterking Javier , Whittaker Rebecca , Joshi Siddarth K. , Birchall Patrick M. , McMillan Alex , Rarity John G. , Matthews Jonathan C. F.
Published: July 2017

Engineering apparatus that harness quantum theory promises to offer practical advantages over current technology. A fundamentally more powerful prospect is that such quantum technologies could out-perform any future iteration of their classical counterparts, no matter how well the attributes of those classical strategies can be improved. Here, for optical direct absorption measurement, we experimentally demonstrate such an instance of an absolute advantage per photon probe that is exposed to the absorbative sample. We use correlated intensity measurements of spontaneous parametric downconversion using a commercially available air-cooled CCD, a new estimator for data analysis and a high heralding efficiency photon-pair source. We show this enables improvement in the precision of measurement, per photon probe, beyond what is achievable with an ideal coherent state (a perfect laser) detected with 100% efficient and noiseless detection. We see this absolute improvement for up to 50% absorption, with a maximum observed factor of improvement of 1.46. This equates to around 32% reduction in the total number of photons traversing an optical sample, compared to any future direct optical absorption measurement using classical light.
Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
Authors: Matz Peggy , Wruck Wasco , Fauler Beatrix , Herebian Diran , Mielke Thorsten , Adjaye James
Published: July 2017

Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes. Furthermore, the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to that of fetal liver and primary human hepatocytes (PHH). K-means clustering identified 100 clusters which include developmental stage-specific groups of genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE stage, DLK and HNF6 the HE stage, HNF4α and Albumin is specific to HLCs, fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene regulatory networks associated with human hepatogenesis and gastrulation in general.
Specific effect of a dopamine partial agonist on counterfactual learning: evidence from Gilles de la Tourette syndrome
Authors: Salvador Alexandre , Worbe Yulia , Delorme Cécile , Coricelli Giorgio , Gaillard Raphaël , Robbins Trevor W. , Hartmann Andreas , Palminteri Stefano
Published: July 2017

The dopamine partial agonist aripiprazole is increasingly used to treat pathologies for which other antipsychotics are indicated because it displays fewer side effects, such as sedation and depression-like symptoms, than other dopamine receptor antagonists. Previously, we showed that aripiprazole may protect motivational function by preserving reinforcement-related signals used to sustain reward-maximization. However, the effect of aripiprazole on more cognitive facets of human reinforcement learning, such as learning from the forgone outcomes of alternative courses of action (i.e., counterfactual learning), is unknown. To test the influence of aripiprazole on counterfactual learning, we administered a reinforcement learning task that involves both direct learning from obtained outcomes and indirect learning from forgone outcomes to two groups of Gilles de la Tourette (GTS) patients, one consisting of patients who were completely unmedicated and the other consisting of patients who were receiving aripiprazole monotherapy, and to healthy subjects. We found that whereas learning performance improved in the presence of counterfactual feedback in both healthy controls and unmedicated GTS patients, this was not the case in aripiprazole-medicated GTS patients. Our results suggest that whereas aripiprazole preserves direct learning of action-outcome associations, it may impair more complex inferential processes, such as counterfactual learning from forgone outcomes, in GTS patients treated with this medication.
Puerarin ameliorated the behavioral deficits induced by chronic stress in rats
Authors: Qiu Zhi-Kun , Zhang Guan-Hua , Zhong De-Sheng , He Jia-Li , Liu Xu , Chen Ji-Sheng , Wei Da-Nian
Published: July 2017

The present study aimed to investigate the mechanisms underlying the antidepressant-like effects of puerarin via the chronic unpredictable stress (CUS) procedure in rats. Similar to Sertraline (Ser), Chronic treatment of puerarin (60 and 120 mg/kg, i.g) elicited the antidepressant-like effects by reversing the decreased sucrose preference in sucrose preference test (SPT), by blocking the increased latency to feed in novelty-suppressed feeding test (NSFT) and the increased immobility time in forced swimming test (FST) without affecting locomotor activity. However, acute puerarin treatment did not ameliorate the antidepressant- and anxiolytic- like effects in FST and NSFT, respectively. In addition, enzyme linked immunosorbent assay (ELISA) and high performance liquid chromatography-electrochemical detection (HPLC-ECD) showed that chronic treatment of puerarin (60 and 120 mg/kg, i.g) reversed the decreased levels of progesterone, allopregnanolone, serotonin (5-HT) and 5-Hydroxyindoleacetic acid (5-HIAA) in prefrontal cortex and hippocampus of post-CUS rats. Furthermore, puerarin (60 and 120 mg/kg, i.g) blocked the increased corticotropin releasing hormone (CRH), corticosterone (Cort) and adrenocorticotropic hormone (ACTH). Collectively, repeated administration of puerarin alleviated the behavioral deficits induced by chronic stress which was associated with the biosynthesis of neurosteroids, normalization of serotonergic system and preventing HPA axis dysfunction.
microRNA-mediated differential expression of TRMU, GTPBP3 and MTO1 in cell models of mitochondrial-DNA diseases
Authors: Meseguer Salvador , Boix Olga , Navarro-González Carmen , Villarroya Magda , Boutoual Rachid , Emperador Sonia , García-Arumí Elena , Montoya Julio , Armengod M.-Eugenia
Published: July 2017

Mitochondrial diseases due to mutations in the mitochondrial (mt) DNA are heterogeneous in clinical manifestations but usually include OXPHOS dysfunction. Mechanisms by which OXPHOS dysfunction contributes to the disease phenotype invoke, apart from cell energy deficit, maladaptive responses to mitochondria-to-nucleus retrograde signaling. Here we used five different cybrid models of mtDNA diseases to demonstrate that the expression of the nuclear-encoded mt-tRNA modification enzymes TRMU, GTPBP3 and MTO1 varies in response to specific pathological mtDNA mutations, thus altering the modification status of mt-tRNAs. Importantly, we demonstrated that the expression of TRMU, GTPBP3 and MTO1 is regulated by different miRNAs, which are induced by retrograde signals like ROS and Ca2+ via different pathways. Our data suggest that the up- or down-regulation of the mt-tRNA modification enzymes is part of a cellular response to cope with a stoichiometric imbalance between mtDNA- and nuclear-encoded OXPHOS subunits. However, this miRNA-mediated response fails to provide full protection from the OXPHOS dysfunction; rather, it appears to aggravate the phenotype since transfection of the mutant cybrids with miRNA antagonists improves the energetic state of the cells, which opens up options for new therapeutic approaches.
Optimization-based design of heat flux manipulation devices with emphasis on fabricability
Authors: Peralta Ignacio , Fachinotti Víctor D.
Published: July 2017

In this work, we present a new method for the design of heat flux manipulating devices, with emphasis on their fabricability. The design is obtained as solution of a nonlinear optimization problem where the objective function represents the given heat flux manipulation task, and the design variables define the material distribution in the device. In order to facilitate the fabrication of the device, the material at a given point is chosen from a set of predefined metamaterials. Each candidate material is assumed to be a laminate of materials with high conductivity contrast, so it is a metamaterial with a highly anisotropic effective conductivity. Following the discrete material optimization (DMO) approach, the fraction of each material at a given finite element of the mesh is defined as a function of continuous variables, which are ultimately the design variables. This DMO definition forces the fraction of each candidate to tend to either zero or one at the optimal solution. As an application example, we designed an easy-to-make device for heat flux concentration and cloaking.
Combined atomic force microscopy and photoluminescence imaging to select single InAs/GaAs quantum dots for quantum photonic devices
Authors: Sapienza Luca , Liu Jin , Song Jin Dong , Fält Stefan , Wegscheider Werner , Badolato Antonio , Srinivasan Kartik
Published: July 2017

We report on a combined photoluminescence imaging and atomic force microscopy study of single, isolated self-assembled InAs quantum dots. The motivation of this work is to determine an approach that allows to assess single quantum dots as candidates for quantum nanophotonic devices. By combining optical and scanning probe characterization techniques, we find that single quantum dots often appear in the vicinity of comparatively large topographic features. Despite this, the quantum dots generally do not exhibit significant differences in their non-resonantly pumped emission spectra in comparison to quantum dots appearing in defect-free regions, and this behavior is observed across multiple wafers produced in different growth chambers. Such large surface features are nevertheless a detriment to applications in which single quantum dots are embedded within nanofabricated photonic devices: they are likely to cause large spectral shifts in the wavelength of cavity modes designed to resonantly enhance the quantum dot emission, thereby resulting in a nominally perfectly-fabricated single quantum dot device failing to behave in accordance with design. We anticipate that the approach of screening quantum dots not only based on their optical properties, but also their surrounding surface topographies, will be necessary to improve the yield of single quantum dot nanophotonic devices.
Mechanically stable fibrin scaffolds promote viability and induce neurite outgrowth in neural aggregates derived from human induced pluripotent stem cells
Authors: Robinson Meghan , Douglas Sarah , Michelle Willerth Stephanie
Published: July 2017

Recent work demonstrated that 3D fibrin scaffolds function as an effective substrate for engineering tissues from pluripotent stem cells. However, the rapid degradation rate of fibrin remains a major limitation when differentiating human pluripotent stem cells for tissue engineering applications. The addition of crosslinking agents, such as genipin, during the polymerization process increases scaffold stability while decreasing the degradation rate of fibrin. Genipin crosslinking alters the physical characteristics of the fibrin scaffolds, which influences the behaviour of the differentiating cells seeded inside. It also possesses neuritogenic and neuroprotective properties, making it particularly attractive for engineering neural tissue from pluripotent stem cells. Here we show that genipin enhances neuronal differentiation of neural progenitors derived from human induced pluripotent stem cells (hiPSCs) in 2D culture and genipin concentration influences the morphological and mechanical properties of 3D fibrin scaffolds. These mechanically stable genipin-crosslinked fibrin scaffolds support hiPSC-derived neural aggregates and induce neurite outgrowth while remaining intact for 2 weeks as opposed to 5 days for unmodified fibrin scaffolds.
Compensatory anabolic signaling in the sarcopenia of experimental chronic arthritis
Authors: Little Robert D. , Prieto-Potin Iván , Pérez-Baos Sandra , Villalvilla Amanda , Gratal Paula , Cicuttini Flavia , Largo Raquel , Herrero-Beaumont Gabriel
Published: July 2017

Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls. Atrogin-1 and MuRF-1 were up-regulated alongside an increase in IL-1β, active NF-κB and a higher ratio of phosphorylated to inactive p38 MAPK. CCL-2 and TNF levels were reduced and IL-6 was unchanged between groups. We observed decreased pSTAT3, unchanged pSTAT1 and Myf5, but increased Pax7, MyoD and myogenin. AiA rabbits had a reduction in myostatin from gastrocnemii and synovium with a congruent decrease in serum myostatin compared to controls. Chronic arthritis induced an RC-like secondary sarcopenia with increased muscle protein breakdown. Elevated IL-1β may trigger proteolysis via elevated NF-κB and p38 MAPK signaling with a compensatory anabolic response suggested by myonuclear expansion, increased Pax7, MyoD and myogenin, reduced pSTAT3 as well as reduced serum, synovial and muscular myostatin.
A rare and extensive summer bloom enhanced by ocean eddies in the oligotrophic western North Pacific Subtropical Gyre
Authors: Chow Chun Hoe , Cheah Wee , Tai Jen-Hua
Published: July 2017

The North Pacific Subtropical Gyre (NPSG) is the largest ecosystem on Earth, and it plays a critical role in global ocean productivity and carbon cycling. Here, we report a rare and striking ~2000-km-long phytoplankton bloom that lasted over one month in the western part of the NPSG in summer 2003. The bloom resulted from the co-occurrence of a northward-shifted North Equatorial Current (NEC) supplying additional phosphate, and strong eddy activity that fueled productivity and spread chlorophyll mainly through horizontal stirring. The extensive one-month bloom had a maximum Chl concentration of six times the summer mean value and collectively fixed an additional five teragrams (5 × 1012 g) of carbon above the summer average. An increase in thepCO2during the bloom suggests that most of the additionally fixed carbon was rapidly consumed.
An in-silico glimpse into the pH dependent structural changes of T7 RNA polymerase: a protein with simplicity
Authors: Borkotoky Subhomoi , Kumar Meena Chetan , Bhalerao Gopalkrishna M. , Murali Ayaluru
Published: July 2017

The capability of performing an array of functions with its single subunit structure makes T7 RNA polymerase (T7RNAP) as one of the simplest yet attractive target for various investigations ranging from structure determinations to several biological tests. In this study, with the help of molecular dynamics (MD) calculations and molecular docking, we investigated the effect of varying pH conditions on conformational flexibility of T7RNAP. We also studied its effect on the interactions with a well established inhibitor (heparin), substrate GTP and T7 promoter of T7RNAP. The simulation studies were validated with the help of three dimensional reconstructions of the polymerase at different pH environments using transmission electron microscopy and single particle analysis. On comparing the simulated structures, it was observed that the structure of T7RNAP changes considerably and interactions with its binding partners also changes as the pH shifts from basic to acidic. Further, it was observed that the C-terminal end plays a vital role in the inefficiency of the polymerase at low pH. Thus, this in-silico study may provide a significant insight into the structural investigations on T7RNAP as well as in designing potent inhibitors against it in varying pH environments.
Neanderthal-Derived Genetic Variation Shapes Modern Human Cranium and Brain
Authors: Gregory Michael D. , Kippenhan J. Shane , Eisenberg Daniel P. , Kohn Philip D. , Dickinson Dwight , Mattay Venkata S. , Chen Qiang , Weinberger Daniel R. , Saad Ziad S. , Berman Karen F.
Published: July 2017

Before their disappearance from the fossil record approximately 40,000 years ago, Neanderthals, the ancient hominin lineage most closely related to modern humans, interbred with ancestors of present-day humans. The legacy of this gene flow persists through Neanderthal-derived variants that survive in modern human DNA; however, the neural implications of this inheritance are uncertain. Here, using MRI in a large cohort of healthy individuals of European-descent, we show that the amount of Neanderthal-originating polymorphism carried in living humans is related to cranial and brain morphology. First, as a validation of our approach, we demonstrate that a greater load of Neanderthal-derived genetic variants (higher “NeanderScore”) is associated with skull shapes resembling those of known Neanderthal cranial remains, particularly in occipital and parietal bones. Next, we demonstrate convergent NeanderScore-related findings in the brain (measured by gray- and white-matter volume, sulcal depth, and gyrification index) that localize to the visual cortex and intraparietal sulcus. This work provides insights into ancestral human neurobiology and suggests that Neanderthal-derived genetic variation is neurologically functional in the contemporary population.
Emergent electronic structure of CaFe2As2
Authors: Ali Khadiza , Maiti Kalobaran
Published: July 2017

CaFe2As2 exhibits collapsed tetragonal (cT) structure and varied exotic behaviour under pressure at low temperatures that led to debate on linking the structural changes to its exceptional electronic properties like superconductivity, magnetism, etc. Here, we investigate the electronic structure of CaFe2As2 forming in different structures employing density functional theory. The results indicate that the stability of the cT phase under pressure arises from the enhancement in hybridization induced effects and shift of the energy bands towards lower energies. The Fermi surface centered around Γ point gradually vanishes with the increase in pressure. Consequently, the nesting between the hole and electron Fermi surfaces associated to the spin density wave state disappears indicating a pathway to achieve the proximity to quantum fluctuations. The magnetic moment at the Fe sites diminishes in the cT phase consistent with the magnetic susceptibility results. Notably, the hybridization of Ca 4s states (Ca-layer may be treated as a charge reservoir layer akin to those in cuprate superconductors) is significantly enhanced in the cT phase revealing its relevance in its interesting electronic properties.
Associations of plasma homocysteine levels with peripheral systolic blood pressure and noninvasive central systolic blood pressure in a community-based Chinese population
Authors: Momin Mohetaboer , Fan Fangfang , Li Jianping , Qin Xianhui , Jia Jia , Qi Litong , Zhang Yan , Huo Yong
Published: July 2017

Previous studies indicated that homocysteine (Hcy) is associated with higher peripheral systolic blood pressure (pSBP). There have been few data on the relationship between Hcy and central SBP (cSBP). A total of 4,364 Chinese subjects from the Shijingshan community in Beijing were included. cSBP and pSBP were measured with an Omron HEM-9000AI device. Subjects were 57.20 ± 8.9 years old, 37.9% were male. The median of Hcy was 11.96 μmol/L. The mean of cSBP and pSBP was 129.94 ± 18.03 mmHg and 133.25 ± 18.58 mmHg. lnHcy was associated with cSBP (adjusted β = 2.17, SE = 0.80, P = 0.007) and pSBP (adjusted β = 2.42, SE = 0.75, P = 0.001). With increasing Hcy, there were enhanced correlations of Hcy with pSBP and cSBP (p for trend between quartiles <0.01). Using Q1 for reference, the Q4 was associated with cSBP (adjusted β = 1.77, SE = 0.89, P = 0.047) and pSBP (adjusted β = 2.15, SE = 0.84, P = 0.011). The correlations were more significant in non-obese subjects than in obese subjects (cSBP: β = 4.30 vs 0.46, pSBP: β = 5.04 vs 1.18, P for interaction <0.001). Our study showed that Hcy was associated with higher cSBP and pSBP, especially in non-obese subjects.
Evaluation of Sofosbuvir (β-D-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine) as an inhibitor of Dengue virus replication
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Authors: Xu Hong-Tao , Colby-Germinario Susan P. , Hassounah Said A. , Fogarty Clare , Osman Nathan , Palanisamy Navaneethan , Han Yingshan , Oliveira Maureen , Quan Yudong , Wainberg Mark A.
Published: July 2017

We evaluated Sofosbuvir (SOF), the anti-hepatitis C virus prodrug of β-d-2′-deoxy-2′-α-fluoro-2′-β-C-methyluridine-5′-monophosphate, for potential inhibitory activity against DENV replication. Both cell-based and biochemical assays, based on use of purified DENV full-length NS5 enzyme, were studied. Cytopathic effect protection and virus yield reduction assays confirmed that SOF possessed anti-DENV activity in cell culture with a 50% effective concentration (EC50) of 4.9 µM and 1.4 µM respectively. Real-time RT-PCR verified that SOF inhibits generation of viral RNA with an EC50 of 9.9 µM. Purified DENV NS5 incorporated the active triphosphate form (SOF-TP) into nascent RNA, causing chain-termination. Relative to the natural UTP, the incorporation efficiency of SOF-TP was low (discrimination value = 327.5). In a primer extension assay, SOF-TP was active against DENV NS5 wild-type polymerase activity with an IC50 of 14.7 ± 2.5 µM. The S600T substitution in the B Motif of DENV polymerase conferred 4.3-fold resistance to SOF-TP; this was due to decreased incorporation efficiency rather than enhanced excision of the incorporated SOF nucleotide. SOF has antiviral activity against DENV replication. The high discrimination value in favor of UTP in enzyme assays may not necessarily preclude antiviral activity in cells. SOF may be worthy of evaluation against severe DENV infections in humans.
Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid
Authors: Ishihara Yasuhiro , Itoh Kouichi , Tanaka Miki , Tsuji Mayumi , Kawamoto Toshihiro , Kawato Suguru , Vogel Christoph F. A. , Yamazaki Takeshi
Published: July 2017

Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic seizures; however, the molecular mechanism by which it achieves this effect is still largely unknown. DHA stimulates the retinoid X receptor, which reportedly regulates the expression of cytochrome P450 aromatase (P450arom). This study aimed to clarify how DHA suppresses seizures, focusing on the regulation of 17β-estradiol synthesis in the brain. Dietary supplementation with DHA increased not only the expression of P450arom, but also 17β-estradiol in the cerebral cortex. While DHA did not affect the duration or scores of the seizures induced by pentylenetetrazole, DHA significantly prolonged the seizure latency. A P450arom inhibitor, letrozole, reduced 17β-estradiol levels and completely suppressed the elongation of seizure latency elicited by DHA. These results suggest that DHA delays the onset of seizures by promoting the synthesis of 17β-estradiol in the brain. DHA upregulated the expression of anti-oxidative enzymes in the cerebral cortex. The oxidation in the cerebral cortex induced by pentylenetetrazole was significantly attenuated by DHA, and letrozole completely inhibited this suppressive action. Thus, the anti-oxidative effects of 17β-estradiol may be involved in the prevention of seizures mediated by DHA. This study revealed that 17β-estradiol in the brain mediated the physiological actions of DHA.
The Frustration-induced Ferroelectricity of a Manganite Tricolor Superlattice with Artificially Broken Symmetry
Authors: Pei Huanyu , Guo Shujin , Ren Lixia , Chen Changle , Luo Bingcheng , Dong Xianglei , Jin Kexin , Ren Ren , Muhammad Zeeshan Hafiz
Published: July 2017

In this paper, [(La0.9Sr0.1MnO3)n/(Pa0.9Ca0.1MnO3)n/(La0.9Sb0.1MnO3)n]m superlattices films have been deposited on (001) Nb:SrTiO3 substrates by a laser molecular-beam epitaxy technology. Expected ferroelectricity arise at well-defined tricolor superlattice at low temperature, composed of transition metal manganite, which is absent in the single-phase compounds. Furthermore, the ferroelectric properties of the superlattices are enhanced by increasing the periodicity m, which may be attributed to the accumulation of the polarization induced by the frustration. As for the magnetic hysteresis loop characteristics of the multilayer structures, the saturation magnetization and magnetic coercivity of films present definitely a strong periodic dependence. It also indicates that the frustration may exist in the tricolor superlattice. Our results further verify the previous theoretical research of generating multiferroics experimentally paving a way for designing or developing the novel magnetoelectric devices based on manganite ferromagnets.
Physical access for residue-mineral interactions controls organic carbon retention in an Oxisol soil
Authors: Ye Chenglong , Bai Tongshuo , Yang Yi , Zhang Hao , Guo Hui , Li Zhen , Li Huixin , Hu Shuijin
Published: July 2017

Oxisol soils are widely distributed in the humid tropical and subtropical regions and are generally characterized with high contents of metal oxides. High metal oxides are believed to facilitate organic carbon (C) accumulation via mineral-organic C interactions but Oxisols often have low organic C. Yet, the causes that constrain organic C accumulation in Oxisol soil are not exactly clear. Here we report results from a microcosm experiment that evaluated how the quantity and size of crop residue fragments affect soil C retention in a typical Oxisol soil in southeast China. We found that there were significantly higher levels of dissolved organic C (DOC), microbial biomass C (MBC) and C accumulation in the heavy soil fraction in soil amended with fine-sized (<0.2 mm) compared with coarse-sized (5.0 mm) fragments. Attenuated total reflectance-Fourier transform infrared spectroscopy analysis further showed that fine-sized residues promoted stabilization of aliphatic C-H and carboxylic C=O compounds associated with mineral phases. In addition, correlation analysis revealed that the increased content of organic C in the heavy soil fraction was positively correlated with increased DOC and MBC. Together, these results suggest that enhancement of contact between organic materials and soil minerals may promote C stabilization in Oxisols.
Preventive effect of celecoxib use against cancer progression and occurrence of oral squamous cell carcinoma
Authors: Chiang Shang-Lun , Velmurugan Bharath Kumar , Chung Chia-Min , Lin Shu-Hui , Wang Zhi-Hong , Hua Chun-Hung , Tsai Ming-Hsui , Kuo Tzer-Min , Yeh Kun-Tu , Chang Pei-Ying , Yang Yi-Hsin , Ko Ying-Chin
Published: July 2017

Overexpression of cyclooxygenase-2 in oral cancer increases lymph node metastasis and is associated with a poor prognosis. The potential of celecoxib (CXB) use is reported in cancer treatment by inhibiting proliferation through apoptosis, but the effects on the epithelial-mesenchymal transition (EMT) and cancer cell mobility remain unclear. We performed a preclinical study and population-based study to evaluate CXB use in the prevention of oral cancer progression and occurrence. The in-vitro findings showed that CXB is involved in the inhibition of EMT and cell mobility through blocking transcription factors (Slug, Snail and ZEB1), cytoplasmic mediators (focal adhesion kinase (FAK), vimentin and β-catenin), cell adhesion molecules (cadherins and integrins), and surface receptors (AMFR and EGFR). The murine xenograft model showed a 65% inhibition in tumour growth after a 5-week treatment of CXB compared to placebo. Xenograft tumours in placebo-treated mice displayed a well-to-moderate/moderate differentiated SCC grade, while those from CXB-treated mice were well differentiated. The expression levels of membrane EGFR, and nuclear FAK, Slug and ZEB1 were decreased in the xenograft tumours of CXB-treated mice. A retrospective cohort study showed that increasing the daily dose and medication time of CXB was associated with oral cancer prevention. The findings provide an alternative prevention strategy for oral cancer development with CXB use.
Quantification of cell-bubble interactions in a 3D engineered tissue phantom
Authors: Walsh C. , Ovenden N. , Stride E. , Cheema U.
Published: July 2017

Understanding cell-bubble interactions is crucial for preventing bubble related pathologies and harnessing their potential therapeutic benefits. Bubbles can occur in the body as a result of therapeutic intravenous administration, surgery, infections or decompression. Subsequent interactions with living cells, may result in pathological responses such as decompression sickness (DCS). This work investigates the interactions that occur between bubbles formed during decompression and cells in a 3D engineered tissue phantom. Increasing the tissue phantoms’ cellular density resulted in decreased dissolved O2 (DO) concentrations (p = 0.0003) measured using real-time O2 monitoring. Direct microscopic observation of these phantoms, revealed a significant (p = 0.0024) corresponding reduction in bubble nucleation. No significant difference in growth rate or maximum size of the bubbles was measured (p = 0.99 and 0.23). These results show that bubble nucleation is dominated by DO concentration (affected by cellular metabolism), rather than potential nucleation sites provided by cell-surfaces. Consequent bubble growth depends not only on DO concentration but also on competition for dissolved gas. Cell death was found to significantly increase (p = 0.0116) following a bubble-forming decompression. By comparison to 2D experiments; the more biomimetic 3D geometry and extracellular matrix in this work, provide data more applicable for understanding and developing models of in vivo bubble dynamics.
Connexin hemichannel blockade improves survival of striatal GABA-ergic neurons after global cerebral ischaemia in term-equivalent fetal sheep
Authors: Galinsky Robert , Davidson Joanne O. , Lear Christopher A. , Bennet Laura , Green Colin R. , Gunn Alistair J.
Published: July 2017

Basal ganglia injury at term remains a major cause of disability, such as cerebral palsy. In this study we tested the hypotheses that blockade of astrocytic connexin hemichannels with a mimetic peptide would improve survival of striatal phenotypic neurons after global cerebral ischaemia in term-equivalent fetal sheep, and that neuronal survival would be associated with electrophysiological recovery. Fetal sheep (0.85 gestation) were randomly assigned to receive a short or long (1 or 25 h) intracerebroventricular infusion of a mimetic peptide or vehicle, starting 90 minutes after 30 minutes of cerebral ischaemia. Sheep were killed 7 days after ischaemia. Cerebral ischaemia was associated with reduced numbers of calbindin-28k, calretinin, parvalbumin and GAD positive striatal neurons (P < 0.05 ischaemia + vehicle, n = 6 vs. sham ischaemia, n = 6) but not ChAT or nNOS positive neurons. Short infusion of peptide (n = 6) did not significantly improve survival of any striatal phenotype. Long infusion of peptide (n = 6) was associated with increased survival of calbindin-28k, calretinin, parvalbumin and GAD positive neurons (P < 0.05 vs. ischaemia + vehicle). Neurophysiological recovery was associated with improved survival of calbindin-28k, calretinin and parvalbumin positive striatal neurons (P < 0.05 for all). In conclusion, connexin hemichannel blockade after cerebral ischaemia in term-equivalent fetal sheep improves survival of striatal GABA-ergic neurons.