bluuebunny/crossref_metadata_2025 huggingface dataset:
Shock-wave reflections over double-concave cylindrical reflectors
Authors: Soni V. , Hadjadj A. , Chaudhuri A. , Ben-Dor G.
Published: January 2017

Numerical simulations were conducted to understand the different wave configurations associated with the shock-wave reflections over double-concave cylindrical surfaces. The reflectors were generated computationally by changing different geometrical parameters, such as the radii of curvature and the initial wedge angles. The incident-shock-wave Mach number was varied such as to cover subsonic, transonic and supersonic regimes of the flows induced by the incident shock. The study revealed a number of interesting wave features starting from the early stage of the shock interaction and transition to transitioned regular reflection (TRR) over the first concave surface, followed by complex shock reflections over the second one. Two new shock bifurcations have been found over the second wedge reflector, depending on the velocity of the additional wave that appears during the TRR over the first wedge reflector. Unlike the first reflector, the transition from a single-triple-point wave configuration (STP) to a double-triple-point wave configuration (DTP) and back occurred several times on the second reflector, indicating that the flow was capable of retaining the memory of the past events over the entire process.
Slip flow past a gas–liquid interface with embedded solid particles
Authors: Vidal A. , Botto L.
Published: January 2017

We simulate shear flow past a stationary monolayer of spherical particles embedded in a flat gas–liquid interface. This problem is relevant to the understanding of the microhydrodynamics of particle-laden interfacial structures, including particle-laden drops, bubbles and foams. The combination of the free-shear condition at the gas–liquid interface and the no-slip condition at the particle surfaces gives rise to a velocity slip at the particle-laden interface. We study the characteristics of the flow near the monolayer, focusing on slip velocity, slip length and interfacial shear stress. Two microstructures are compared: a square array, and a reticulated array mimicking a percolating network of aggregated particles. We demonstrate that the scaling laws for the dependence of the slip length on solid area fraction developed for flow past superhydrophobic microstructured surfaces apply to the case of interfacial particles. The calculated slip lengths are in general smaller that those reported for microstructured superhydrophobic surfaces. This difference, which is due to the significant protrusion of the spherical particles in the liquid, can be accounted for in the case of the square array by an approximate argument. For a given area fraction, the reticulated array yields a larger slip length than the square array. We analyse the hydrodynamic forces acting on the particles, and the corresponding tangential stress exerted by the bulk ‘subphase’.
The syntax of semantic agreement in English
Authors: SMITH PETER W.
Published: January 2017

This paper investigates the properties of plural agreement that is triggered by collective nouns in British English. Both singular and plural agreement are able to appear with these collective nouns, which are shown to be morphologically singular but semantically plural. Plural agreement, however, is systematically more restricted than singular agreement, appearing in a subset of the environments where singular agreement is allowed. Restrictions on plural come from the nature of agreement; semantic agreement features can only enter into agreement when the controller of agreement c-commands the target of agreement, whereas morphologically motivated agreement is not subject to the same structural restriction. This asymmetry between the two types of agreement is shown to arise from the proposal thatAgree(Chomsky 2000, 2001) is distributed over the syntactic and post-syntactic components (Arregi & Nevins 2012).
Structural biology of supramolecular assemblies by magic-angle spinning NMR spectroscopy
Authors: Quinn Caitlin M. , Polenova Tatyana
Published: January 2017

In recent years, exciting developments in instrument technology and experimental methodology have advanced the field of magic-angle spinning (MAS) nuclear magnetic resonance (NMR) to new heights. Contemporary MAS NMR yields atomic-level insights into structure and dynamics of an astounding range of biological systems, many of which cannot be studied by other methods. With the advent of fast MAS, proton detection, and novel pulse sequences, large supramolecular assemblies, such as cytoskeletal proteins and intact viruses, are now accessible for detailed analysis. In this review, we will discuss the current MAS NMR methodologies that enable characterization of complex biomolecular systems and will present examples of applications to several classes of assemblies comprising bacterial and mammalian cytoskeleton as well as human immunodeficiency virus 1 and bacteriophage viruses. The body of work reviewed herein is representative of the recent advancements in the field, with respect to the complexity of the systems studied, the quality of the data, and the significance to the biology.
Normal-order reduction grammars
Authors: BENDKOWSKI MACIEJ
Published: January 2017

We present an algorithm which, for given n, generates an unambiguous regular tree grammar defining the set of combinatory logic terms, over the set {S, K} of primitive combinators, requiring exactly n normal-order reduction steps to normalize. As a consequence of Curry and Feys's standardization theorem, our reduction grammars form a complete syntactic characterization of normalizing combinatory logic terms. Using them, we provide a recursive method of constructing ordinary generating functions counting the number of SK-combinators reducing in n normal-order reduction steps. Finally, we investigate the size of generated grammars giving a primitive recursive upper bound.
POLITICAL CAPITALISM IN THE GILDED AGE: THE TAMMANY BANK RUN OF 1871
Authors: Broxmeyer Jeffrey D.
Published: January 2017

The Tweed Ring spawned a vibrant financial sector that was integral to its brief success but has never been previously examined. William “Boss” Tweed and his allies employed banks controlled or comanaged by Tammany politicians to embezzle funds, build political alliances, and invest in a wide array of business ventures. The capital of these savings and commercial banks—city money, deposits from Catholic charities, and the savings of immigrant laborers—was accumulated through political channels. During their operation between 1867 and 1871, politician-bankers engaged in a mix of patronage deals and profit-driven financial speculation. In effect, Tammany banks were ground zero for the Ring's conversion of political hegemony into a windfall of economic capital that fueled party activities and buoyed personal fortunes. Importantly, the anti-Ring mobilization by upper-class reformers was more than a revolt of wealthy taxpayers concerned with abstract goals of good government or rescuing city credit; it was also a reaction by old-line bankers in direct competition with Tammany upstarts. A dramatic bank run catalyzed by reformers in November 1871 drove them into bankruptcy, bringing this novel experiment in political capitalism to an end.
SCHOOLS ON PARADE: PATRIOTISM AND THE TRANSFORMATION OF URBAN EDUCATION AT THE DAWN OF THE PROGRESSIVE ERA
Authors: Ewert Cody Dodge
Published: January 2017

As the scope and power of public school systems across the United States grew during the Progressive Era, so too did a popular belief that mass education could solve the major social and political problems of the day. This in part owes to school reformers’ efforts to frame public education as an inherently patriotic institution that if properly supported could move the nation forward while preserving its history and traditions. Their efforts centered on the Columbian School Celebration, a nationwide school parade corresponding with the four-hundredth anniversary of Columbus's arrival in the Americas. A case study focusing on a key place and time in this movement's history––Brooklyn, New York, in the early 1890s––this article explores how progressive educators in Brooklyn both used patriotism as a rhetorical device to excite popular support and proclaimed it the cornerstone of the modern urban schools they hoped to build. In so doing, it helps explain both the rise of large urban school systems and growing salience of educational matters in twentieth-century politics.
Which electoral systems succeed at providing proportionality and concentration? Promising designs and risky tools
Authors: Raabe Johannes , Linhart Eric
Published: January 2017

Electoral systems are typically faced with the problem of being asked to provide both proportional representation and party system concentration leading to accountable government. Which electoral system designs are able to successfully deliver on both these challenges and thus optimize the representativeness – accountability trade-off? This paper investigates the performance of different general electoral system designs as well as their specific technical details (such as legal threshold, tier linkages, and compensation mechanisms) based on a data set of 590 elections in 57 countries. The key results are that both proportional representation systems with moderate district magnitudes and mixed-member proportional systems are able to optimize performance. Going to the level of details confirms these results and deepens our understanding further: while different technical changes are able to improve the chances of reaching the best of both worlds, some of these (e.g. raising the legal threshold) also increase the risk of ending up with the worst.
Cardiac afferent activity modulates the expression of racial stereotypes
Authors: Azevedo Ruben T. , Garfinkel Sarah N. , Critchley Hugo D. , Tsakiris Manos
Published: January 2017

Negative racial stereotypes tend to associate Black people with threat. This often leads to the misidentification of harmless objects as weapons held by a Black individual. Yet, little is known about how bodily states impact the expression of racial stereotyping. By tapping into the phasic activation of arterial baroreceptors, known to be associated with changes in the neural processing of fearful stimuli, we show activation of race-threat stereotypes synchronized with the cardiovascular cycle. Across two established tasks, stimuli depicting Black or White individuals were presented to coincide with either the cardiac systole or diastole. Results show increased race-driven misidentification of weapons during systole, when baroreceptor afferent firing is maximal, relative to diastole. Importantly, a third study examining the positive Black-athletic stereotypical association fails to demonstrate similar modulations by cardiac cycle. We identify a body–brain interaction wherein interoceptive cues can modulate threat appraisal and racially biased behaviour in context-dependent ways.
Genetic Polymorphisms of rs3077 and rs9277535 in HLA-DP associated with Systemic lupus erythematosus in a Chinese population
Authors: Zhang Junlong , Zhan Wenli , Yang Bin , Tian Anning , Chen Lin , Liao Yun , Wu Yongkang , Cai Bei , Wang Lanlan
Published: January 2017

Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4+ T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE. In total, samples from 335 SLE patients and 635 healthy controls were collected and genotyped by a polymerase chain reaction-high resolution melting (PCR-HRM) assay. A significant positive correlation was observed between the SNP rs3077, rs9277535 of HLA-DP and SLE susceptibility (rs3077, OR = 0.74, 95%CI = 0.60–0.91, P = 0.004; rs9277535, OR = 0.72, 95%CI = 0.59–0.88, P = 0.001). Rs3077 polymorphism was corelated to IL-17, INF-γ and cutaneous vasculitis (P = 0.037, P = 0.020 and P = 0.006, respectively). Additionally, rs3077 AA genotype carriers showed lower concentration of inflammatory cytokines and lower cutaneous vasculitis incidence than did the other two genotype. No significant association was observed between rs9277535 and cytokines or any clinical features. In conclusion, HLA-DP polymorphisms (rs3077 and rs9277535) were associated with SLE susceptibility and the levels of some inflammatory cytokines in SLE patients.
Estrogen related receptor is required for the testicular development and for the normal sperm axoneme/mitochondrial derivatives in Drosophila males
Authors: Misra Snigdha , Pandey Anuj Kumar , Gupta Snigdha , Kumar Ajay , Khanna Priyanka , shankar Jai , Ravi Ram Kristipati
Published: January 2017

Estrogen related receptors (ERRs), categorized as orphan nuclear receptors, are critical for energy homeostasis and somatic development. However, significance of ERRs in the development of reproductive organs/organelles/cells remain poorly understood, albeit their homology to estrogen receptors. In this context, here, we show that knockdown of ERR in the testes leads to improperly developed testes with mis-regulation of genes (aly, mia, bruce, bam, bgcn, fzo and eya) involved in spermatogenesis, resulting in reduced male fertility. The observed testicular deformity is consistent with the down-regulation of SOX-E group of gene (SOX100B) in Drosophila. We also show dispersion/disintegration of fusomes (microtubule based structures associated with endoplasmic reticulum derived vesicle, interconnecting spermatocytes) in ERR knockdown testes. A few ERR knockdown testes go through spermatogenesis but have significantly fewer sperm. Moreover, flagella of these sperm are defective with abnormal axoneme and severely reduced mitochondrial derivatives, suggesting a possible role for ERR in mitochondrial biogenesis, analogous to mammalian ERRα. Interestingly, similar knockdown of remaining seventeen nuclear receptors did not yield a detectable reproductive or developmental defect in Drosophila. These findings add newer dimensions to the functions envisaged for ERR and provide the foundation for deciphering the relevance of orphan nuclear receptors in ciliopathies and testicular dysgenesis.
B7-H3 participates in the development of Asthma by augmentation of the inflammatory response independent of TLR2 pathway
Authors: Gu Wenjing , Zhang Xinxing , Yan Yongdong , Wang Yuqing , Huang Li , Wang Meijuan , Shao Xuejun , Chen Zhengrong , Ji Wei
Published: January 2017

B7-H3, a new member of the B7 superfamily, acts as both a T cell costimulator and coinhibitor. Recent studies identified B7-H3 plays a critical role in the development of asthma. But the definitive mechanism is not clear. In this study, we further report that B7-H3 participates in the development of OVA-induced asthma in a murine model. And study its mechanism through the vitro and vivo experiment. Exogenous administration of B7-H3 strongly amplified the inflammatory response and augmented proinflammatory cytokines in vitro and vivo. These B7-H3–associated proinflammatory effects were not dependent on TLR2 signaling, as airway inflammation, eosinophils infiltration and cytokins (IL-4, IL-5, IL-13 and IFN-gamma) augment were still amplified in TLR2-deficient mice after administrated recombinant mouse B7-H3. These results indicated an important role for B7-H3 in the development of Th1 and Th2 cells in a murine model of asthma and its proinflammatory effects are not dependent on TLR2 signaling.
Evidence of neofunctionalization after the duplication of the highly conserved Polycomb group gene Caf1-55 in the obscura group of Drosophila
Authors: Calvo-Martín Juan M. , Papaceit Montserrat , Segarra Carmen
Published: January 2017

Drosophila CAF1-55 protein is a subunit of the Polycomb repressive complex PRC2 and other protein complexes. It is a multifunctional and evolutionarily conserved protein that participates in nucleosome assembly and remodelling, as well as in the epigenetic regulation of a large set of target genes. Here, we describe and analyze the duplication of Caf1-55 in the obscura group of Drosophila. Paralogs exhibited a strong asymmetry in evolutionary rates, which suggests that they have evolved according to a neofunctionalization process. During this process, the ancestral copy has been kept under steady purifying selection to retain the ancestral function and the derived copy (Caf1-55dup) that originated via a DNA-mediated duplication event ~18 Mya, has been under clear episodic selection. Different maximum likelihood approaches confirmed the action of positive selection, in contrast to relaxed selection, on Caf1-55dup after the duplication. This adaptive process has also taken place more recently during the divergence of D. subobscura and D. guanche. The possible association of this duplication with a previously detected acceleration in the evolutionary rate of three CAF1-55 partners in PRC2 complexes is discussed. Finally, the timing and functional consequences of the Caf1-55 duplication is compared to other duplications of Polycomb genes.
The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin
Authors: Cazzaniga Alessandra , Moscheni Claudia , Trapani Valentina , Wolf Federica I. , Farruggia Giovanna , Sargenti Azzurra , Iotti Stefano , Maier Jeanette A. M. , Castiglioni Sara
Published: January 2017

The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other “staminal” traits.
Peripheral arterial volume distensibility changes with applied external pressure: significant difference between arteries with different compliance
Authors: Chen Mengyan , Chen Aiqing , Si Xiaoshui , Ji Mingxia , Zheng Dingchang
Published: January 2017

This study aimed to quantify the different effect of external cuff pressure on arterial volume distensibility between peripheral arteries with different compliance. 30 healthy subjects were studied with the arm at two positions (0° and 45° from the horizontal level) to introduce different compliance of arteries. The electrocardiogram and finger and ear photoplethysmograms were recorded simultaneously under five external cuff pressures (0, 10, 20, 30 and 40 mmHg) on the whole arm to obtain arterial volume distensibility. With the applied external cuff pressures of 10, 20, 30 and 40 mmHg, the overall changes in arterial volume distensibility referred to those without external pressure were 0.010, 0.029, 0.054 and 0.108% per mmHg for the arm at the horizontal level, and 0.026, 0.071, 0.170 and 0.389% per mmHg for the arm at 45° from the horizontal level, confirming the non-linearity between arterial volume distensibility and external pressure. More interestingly, the significant differences in arterial volume distensibility changes were observed between the two arm positions, which were 0.016, 0.043, 0.116 and 0.281% per mmHg (all P < 0.01). Our findings demonstrated that arterial volume distensibility of peripheral arm arteries increased with external pressure, with a greater effect for more compliant arteries.
Endozoicomonas genomes reveal functional adaptation and plasticity in bacterial strains symbiotically associated with diverse marine hosts
Authors: Neave Matthew J. , Michell Craig T. , Apprill Amy , Voolstra Christian R.
Published: January 2017

Endozoicomonas bacteria are globally distributed and often abundantly associated with diverse marine hosts including reef-building corals, yet their function remains unknown. In this study we generated novel Endozoicomonas genomes from single cells and metagenomes obtained directly from the corals Stylophora pistillata, Pocillopora verrucosa, and Acropora humilis. We then compared these culture-independent genomes to existing genomes of bacterial isolates acquired from a sponge, sea slug, and coral to examine the functional landscape of this enigmatic genus. Sequencing and analysis of single cells and metagenomes resulted in four novel genomes with 60–76% and 81–90% genome completeness, respectively. These data also confirmed that Endozoicomonas genomes are large and are not streamlined for an obligate endosymbiotic lifestyle, implying that they have free-living stages. All genomes show an enrichment of genes associated with carbon sugar transport and utilization and protein secretion, potentially indicating that Endozoicomonas contribute to the cycling of carbohydrates and the provision of proteins to their respective hosts. Importantly, besides these commonalities, the genomes showed evidence for differential functional specificity and diversification, including genes for the production of amino acids. Given this metabolic diversity of Endozoicomonas we propose that different genotypes play disparate roles and have diversified in concert with their hosts.
Differential Effects of Vitamins A and D on the Transcriptional Landscape of Human Monocytes during Infection
Authors: Klassert Tilman E. , Bräuer Julia , Hölzer Martin , Stock Magdalena , Riege Konstantin , Zubiría-Barrera Cristina , Müller Mario M. , Rummler Silke , Skerka Christine , Marz Manja , Slevogt Hortense
Published: January 2017

Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.
Californium-252 neutron intracavity brachytherapy alone for T1N0 low-lying rectal adenocarcinoma: A definitive anal sphincter-preserving radiotherapy
Authors: Xiong Yanli , Shan Jinlu , Liu Jia , Zhao Kewei , Chen Shu , Xu Wenjing , Zhou Qian , Yang Mei , Lei Xin
Published: January 2017

This study evaluated the 4-year results of 32 patients with T1N0 low-lying rectal adenocarcinoma treated solely with californium-252 (Cf-252) neutron intracavity brachytherapy (ICBT). Patients were solicited into the study from January 2008 to June 2011. All the patients had refused surgery or surgery was contraindicated. The patients were treated with Cf-252 neutron ICBT using a novel 3.5-cm diameter off-axis 4-channel intrarectal applicator designed by the authors. The dose reference point was defined on the mucosa surface, with a total dose of 55–62 Gy-eq/4 f (13–16 Gy-eq/f/wk). All the patients completed the radiotherapy in accordance with our protocol. The rectal lesions regressed completely, and the acute rectal toxicity was mild (≤G2). The 4-year local control, overall survival, disease-free survival, and late complication (≥G2) rates were 96.9%, 90.6%, 87.5% and 15.6%, respectively. No severe late complication (≥G3) occurred. The mean follow-up was 56.1 ± 16.0 months. At the end of last follow-up, 29 patients remained alive. The mean survival time was 82.1 ± 2.7 months. Cf-252 neutron ICBT administered as the sole treatment (without surgery) for patients with T1N0 low-lying rectal adenocarcinoma is effective with acceptable late complications. Our study and method offers a definitive anal sphincter-preserving radiotherapy for T1N0 low-lying rectal adenocarcinoma patients.
Methane Emissions and Microbial Communities as Influenced by Dual Cropping of Azolla along with Early Rice
Authors: Liu Jingna , Xu Heshui , Jiang Ying , Zhang Kai , Hu Yuegao , Zeng Zhaohai
Published: January 2017

Azolla caroliniana Willd. is widely used as a green manure accompanying rice, but its ecological importance remains unclear, except for its ability to fix nitrogen in association with cyanobacteria. To investigate the impacts of Azolla cultivation on methane emissions and environmental variables in paddy fields, we performed this study on the plain of Dongting Lake, China, in 2014. The results showed that the dual cropping of Azolla significantly suppressed the methane emissions from paddies, likely due to the increase in redox potential in the root region and dissolved oxygen concentration at the soil-water interface. Furthermore, the floodwater pH decreased in association with Azolla cultivation, which is also a factor significantly correlated with the decrease in methane emissions. An increase in methanotrophic bacteria population (pmoA gene copies) and a reduction in methanogenic archaea (16S rRNA gene copies) were observed in association with Azolla growth. During rice cultivation period, dual cropping of Azolla also intensified increasing trend of 1/Simpson of methanogens and significantly decreased species richness (Chao 1) and species diversity (1/Simpson, 1/D) of methanotrophs. These results clearly demonstrate the suppression of CH4 emissions by culturing Azolla and show the environmental and microbial responses in paddy soil under Azolla cultivation.
Cocaine Enhances DC to T-cell HIV-1 Transmission by Activating DC-SIGN/LARG/LSP1 Complex and Facilitating Infectious Synapse Formation
Authors: Prasad Anil , Kulkarni Rutuja , Jiang Shuxian , Groopman Jerome E.
Published: January 2017

DC-SIGN is a dendritic cell surface structure which participates in binding and transmission of HIV-1. Here, for the first time we demonstrate that cocaine induces over expression of DC-SIGN and significantly enhances virus transfer from DCs to T-cells by increasing the binding and internalization of HIV-1 in DCs. We found that cocaine activates a DC-SIGN mediated ‘signalosome’ complex by enhancing its association with LARG and LSP1. Further, LARG was observed to participate in DC-SIGN mediated internalization of HIV-1 in DCs. Intracellular trafficking studies of HIV-1 in cocaine treated DCs revealed increased co-localization of HIV-1 with endosomal or multi vesicular body (MVB) markers such as CD81 and VPS4 and decreased co-localization with the phagolysomal marker LAMP1; this signified altered intracellular trafficking and decreased degradation of HIV-1 in cocaine treated DCs. Furthermore, we found that cocaine induced activation of LARG which in turn activated Rho A and the focal adhesion molecules FAK, Pyk2 and paxillin. This signaling cascade enhanced the formation of an infectious synapse between DCs and T-cells. Our study provides insight into the molecular mechanisms of cocaine’s contribution to key components in HIV pathogenesis and highlights novel targets for interrupting the virus life cycle in substance using hosts.
Adipocyte Fatty Acid Binding Protein Potentiates Toxic Lipids-Induced Endoplasmic Reticulum Stress in Macrophages via Inhibition of Janus Kinase 2-dependent Autophagy
Authors: Hoo Ruby L. C. , Shu Lingling , Cheng Kenneth K. Y. , Wu Xiaoping , Liao Boya , Wu Donghai , Zhou Zhiguang , Xu Aimin
Published: January 2017

Lipotoxicity is implicated in the pathogenesis of obesity-related inflammatory complications by promoting macrophage infiltration and activation. Endoplasmic reticulum (ER) stress and adipocyte fatty acid binding protein (A-FABP) play key roles in obesity and mediate inflammatory activity through similar signaling pathways. However, little is known about their interplay in lipid-induced inflammatory responses. Here, we showed that prolonged treatment of palmitic acid (PA) increased ER stress and expression of A-FABP, which was accompanied by reduced autophagic flux in macrophages. Over-expression of A-FABP impaired PA-induced autophagy associating with enhanced ER stress and pro-inflammatory cytokine production, while genetic ablation or pharmacological inhibition of A-FABP reversed the conditions. PA-induced expression of autophagy-related protein (Atg)7 was attenuated in A-FABP over-expressed macrophages, but was elevated in A-FABP-deficient macrophages. Mechanistically, A-FABP potentiated the effects of PA by inhibition of Janus Kinase (JAK)2 activity, thus diminished PA-induced Atg7 expression contributing to impaired autophagy and further augmentation of ER stress. These findings suggest that A-FABP acts as autophagy inhibitor to instigate toxic lipids-induced ER stress through inhibition of JAK2-dependent autophagy, which in turn triggers inflammatory responses in macrophages. A-FABP-JAK2 axis may represent an important pathological pathway contributing to obesity-related inflammatory diseases.
Extrinsic MAVS signaling is critical for Treg maintenance of Foxp3 expression following acute flavivirus infection
Authors: Da Costa Andreia , Garza Esteban , Graham Jessica B. , Swarts Jessica L. , Soerens Andrew G. , Gale Michael , Lund Jennifer M.
Published: January 2017

Given the rapid spread of flaviviruses such as West Nile virus (WNV) and Zika virus, it is critical that we develop a complete understanding of the key mediators of an effective anti-viral response. We previously demonstrated that WNV infection of mice deficient in mitochondrial antiviral-signaling protein (MAVS), the signaling adaptor for RNA helicases such as RIG-I, resulted in increased death and dysregulated immunity, which correlated with a failure of Treg expansion following infection. Thus, we sought to determine if intrinsic MAVS signaling is required for participation of Tregs in anti-WNV immunity. Despite evidence of increased Treg cell division, Foxp3 expression was not stably maintained after WNV infection in MAVS-deficient mice. However, intrinsic MAVS signaling was dispensable for Treg proliferation and suppressive capacity. Further, we observed generation of an effective anti-WNV immune response when Tregs lacked MAVS, thereby demonstrating that Treg detection of the presence of WNV through the MAVS signaling pathway is not required for generation of effective immunity. Together, these data suggest that while MAVS signaling has a considerable impact on Treg identity, this effect is not mediated by intrinsic MAVS signaling but rather is likely an effect of the overproduction of pro-inflammatory cytokines generated in MAVS-deficient mice after WNV infection.
The genome sequence of Barbarea vulgaris facilitates the study of ecological biochemistry
Authors: Byrne Stephen L. , Erthmann Pernille Østerbye , Agerbirk Niels , Bak Søren , Hauser Thure Pavlo , Nagy Istvan , Paina Cristiana , Asp Torben
Published: January 2017

The genus Barbarea has emerged as a model for evolution and ecology of plant defense compounds, due to its unusual glucosinolate profile and production of saponins, unique to the Brassicaceae. One species, B. vulgaris, includes two ‘types’, G-type and P-type that differ in trichome density, and their glucosinolate and saponin profiles. A key difference is the stereochemistry of hydroxylation of their common phenethylglucosinolate backbone, leading to epimeric glucobarbarins. Here we report a draft genome sequence of the G-type, and re-sequencing of the P-type for comparison. This enables us to identify candidate genes underlying glucosinolate diversity, trichome density, and study the genetics of biochemical variation for glucosinolate and saponins. B. vulgaris is resistant to the diamondback moth, and may be exploited for “dead-end” trap cropping where glucosinolates stimulate oviposition and saponins deter larvae to the extent that they die. The B. vulgaris genome will promote the study of mechanisms in ecological biochemistry to benefit crop resistance breeding.
MiR-124 inhibits the migration and invasion of human hepatocellular carcinoma cells by suppressing integrin αV expression
Authors: Cai Qian Qian , Dong Yi Wei , Wang Rong , Qi Bing , Guo Jun Xia , Pan Jing , Liu Yuan Yuan , Zhang Chun Yi , Wu Xing Zhong
Published: January 2017

Tumor metastasis is the major cause of cancer-related death especially in human hepatocellular carcinoma (HCC). Although microRNAs have been implicated in tumor development, the roles of miR-124 in HCC metastasis are still not well understood. We conducted functional analysis in this study to investigate miR-124. We observed that miR-124 significantly retarded the wound healing and migration of HCC SMMC-7721 and BEL-7404 cells. Further analysis indicated miR-124 directly targeting the transcriptional factor Sp1 which is an important transcription factor for the integrin αV subunit gene transcription. Co-transfection of miR-124 with the luciferase reporter containing Sp1 3′ untranslated region (UTR) significantly suppressed the luciferase activities. While mutation of the binding site of miR-124 in Sp1 mRNA 3′UTR completely abrogated the suppression of miR-124. Overexpression of miR-124 resulted in robust downregulation of Sp1 and integrin αV expression at either mRNA or protein level. Ectopic expression of miR-124 in HCC dramatically repressed the wound healing and migration in vitro and tumor metastasis in mouse experiments. Our findings demonstrated that miR-124 played as an important role in regulation of integrin αV expression in HCC, and reintroduction of miR-124 might be an alternative therapeutic strategy for controlling integrin αV expression in HCC.
Remission of lymphoblastic leukaemia in an intravascular fluidic environment by pliable drug carrier with a sliding target ligand
Authors: Jang Donghyun , Lee Yeong Mi , Lee Jaehyun , Doh Junsang , Kim Won Jong
Published: January 2017

A polyrotaxane-based nanoconstruct with pliable structure carrying a chemotherapeutic drug was developed for targeting circulating lymphoblastic leukaemia cells in a fluidic environment of blood vessels in vivo. By introducing lymphoblast targeting aptamer DNA through cyclodextrin, threaded in poly(ethylene glycol) as polyrotaxane, target aptamer slides along the long polymeric chain and actively search for target ligand, leading to active targeting in dynamic fluidic system which is enhanced by up to 6–fold compared with that of control carriers with non–sliding targeting ligands. Moreover, the drug carrier was made stimuli-responsive by employing i-motif DNA to selective releases of its payload at intracellular acidic condition. These combined features resulted in the effective remission of lymphoblastic leukaemia both in vitro and in dynamic blood vessels in vivo.
Maternal diabetes modulates dental epithelial stem cells proliferation and self-renewal in offspring through apurinic/apyrimidinicendonuclease 1-mediated DNA methylation
Authors: Chen Guoqing , Chen Jie , Yan Zhiling , Li Ziyue , Yu Mei , Guo Weihua , Tian Weidong
Published: January 2017

Maternal gestational diabetes mellitus (GDM) has many adverse effects on the development of offspring. Aberrant DNA methylation is a potential mechanism associated with these effects. However, the effects of GDM on tooth development and the underlying mechanisms have not been thoroughly investigated. In the present study, a GDM rat model was established and incisor labial cervical loop tissue and dental epithelial stem cells (DESCs) were harvested from neonates of diabetic and control dams. GDM significantly suppressed incisor enamel formation and DESCs proliferation and self-renewal in offspring. Gene expression profiles showed that Apex1 was significantly downregulated in the offspring of diabetic dams. In vitro, gain and loss of function analyses showed that APEX1 was critical for DESCs proliferation and self-renewal and Oct4 and Nanog regulation via promoter methylation. In vivo, we confirmed that GDM resulted in significant downregulation of Oct4 and Nanog and hypermethylation of their promoters. Moreover, we found that APEX1 modulated DNA methylation by regulating DNMT1 expression through ERK and JNK signalling. In summary, our data suggest that GDM-induced APEX1 downregulation increased DNMT1 expression, thereby inhibiting Oct4 and Nanog expression, through promoter hypermethylation, resulting in suppression of DESCs proliferation and self-renewal, as well as enamel formation.
A transcriptome analysis focusing on inflammation-related genes of grass carp intestines following infection with Aeromonas hydrophila
Authors: Song Xuehong , Hu Xiaolong , Sun Bingyao , Bo Yunxuan , Wu Kang , Xiao Lanying , Gong Chengliang
Published: January 2017

Inflammation is a protective response that is implicated in bacterial enteritis and other fish diseases. The inflammatory mechanisms behindAeromonas hydrophilainfections in fish remain poorly understood. In this study, we performed ade novograss carp transcriptome assembly using Illumina’s Solexa sequencing technique. On this basis we carried out a comparative analysis of intestinal transcriptomes fromA. hydrophila-challenged and physiological saline solution (PSS/mock) -challenged fish, and 315 genes were up-regulated and 234 were down-regulated in the intestines infected withA. hydrophila. The GO enrichment analysis indicated that the differentially expressed genes were enriched to 12, 4, and 8 GO terms in biological process, molecular function, and cellular component, respectively. A KEGG analysis showed that 549 DEGs were involved in 165 pathways. Moreover, 15 DEGs were selected for quantitative real-time PCR analysis to validate the RNA-seq data. The results confirmed the consistency of the expression levels between RNA-seq and qPCR data. In addition, a time-course analysis of the mRNA expression of 12 inflammatory genes further demonstrated that the intestinal inflammatory responses toA. hydrophilainfection simultaneously modulated gene expression variations. The present study provides intestine-specific transcriptome data, allowing us to unravel the mechanisms of intestinal inflammation triggered by bacterial pathogens.
The usefulness of CorvisST Tonometry and the Ocular Response Analyzer to assess the progression of glaucoma
Authors: Matsuura Masato , Hirasawa Kazunori , Murata Hiroshi , Nakakura Shunsuke , Kiuchi Yoshiaki , Asaoka Ryo
Published: January 2017

Corneal Visualization Scheimpflug Technology (CST) and Ocular Response Analyzer (ORA) measurements were carried out in 105 eyes of 69 patients with primary open-angle glaucoma. All patients had axial length (AL), central corneal thickness (CCT), intraocular pressure (IOP) with Goldmann applanation tonometry (GAT) and eight visual fields (VF)s with the Humphrey Field Analyzer. VF progression was summarized using a time trend analysis of mean total deviation (mTD) and the association between mTD progression rate and a number of ocular parameters (including CST and ORA measurements) was assessed using mixed linear regression analysis. The optimal model of VF progression selected based on the corrected Akaike Information Criteria (AICc) included ORA’s corneal hysteresis (CH) parameter as well as a number of CST measurements: mTD progression rate = 1.2–0.070 * mean GAT + 0.090 * CH–1.5 * highest concavity deformation amplitude with CST + 9.4 * A1 deformation amplitude with CST–0.05 * A2 length with CST (AICc = 125.8). Eyes with corneas that experience deep indentation at the maximum deformation, shallow indentation at the first applanation and wide indentation at the second applanation in the CST measurement are more likely to experience faster rates of VF progression.
Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target
Authors: Sizdahkhani Saman , Feldman Michael J. , Piazza Martin G. , Ksendzovsky Alexander , Edwards Nancy A. , Ray-Chaudhury Abhik , Maric Dragan , Merrill Marsha J. , Pacak Karel , Zhuang Zhengping , Chittiboina Prashant
Published: January 2017

Von Hippel-Lindau (VHL)-associated hemangioblastomas (VHL-HB) arise in the central nervous system (CNS), and are a leading cause of morbidity and mortality in VHL disease. Currently, surgical resection is the most effective way to manage symptomatic VHL-HBs. Surgically unresectable VHL-HBs or those in frail patients are challenging problems. Therapies targeting oncologic and vascular endothelial growth factor (VEGF) pathways have failed to demonstrate tumor control. Our experience and previous reports on VHL-HB avidity to somatostatin analogues suggested somatostatin receptor (SSTR) expression in VHL-HBs, offering an alternative therapeutic strategy. We explored this possibility by demonstrating consistent histologic expression of SSTR1, 2a, 4, and 5 in VHL-HBs. We found that somatostatin analogue octreotide induces apoptosis in VHL-HB stromal cells in a dose-dependent fashion by BAX – caspase-3 pathway unrelated to canonical VHL pathway. When administered to a patient with unresectable symptomatic suprasellar hemangioblastoma, octreotide resulted in tumor volume reduction, symptom stabilization, and tumor cytopenia on repeat 68Ga-DOTA-TATE positron emission tomography (PET) within 6 months, suggesting tumor infarction. We conclude that VHL-HBs harbor multiple SSTR subtypes that offer actionable chemo-therapeutic strategy for management of symptomatic, unresectable tumors by somatostatin analogue therapy.
Significantly enhanced creep resistance of low volume fraction in-situ TiBw/Ti6Al4V composites by architectured network reinforcements
Authors: Wang S. , Huang L. J. , Geng L. , Scarpa F. , Jiao Y. , Peng H. X.
Published: January 2017

We present a new class of TiBw/Ti6Al4V composites with a network reinforcement architecture that exhibits a significant creep resistance compared to monolithic Ti6Al4V alloys. Creep tests performed at temperatures between 773 K and 923 K and stress range of 100 MPa-300 MPa indicate both a significant improvement of the composites creep resistance due to the network architecture made by the TiB whiskers (TiBw), and a decrease of the steady-state creep rates by augmenting the local volume fractions of TiBw in the network region. The deformation behavior is driven by a diffusion-controlled dislocation climb process. Moreover, the activation energies of these composites are significantly higher than that of Ti6Al4V alloys, indicating a higher creep resistance. The increase of the activation energy can be attributed to the TiBw architecture that severely impedes the movements of dislocation and grain boundary sliding and provides a tailoring of the stress transfer. These micromechanical mechanisms lead to a remarkable improvement of the creep resistance of these networked TiBw/Ti6Al4V composites featuring the special networked architecture.
DRD2 co-expression network and a related polygenic index predict imaging, behavioral and clinical phenotypes linked to schizophrenia
Authors: Pergola G , Di Carlo P , D'Ambrosio E , Gelao B , Fazio L , Papalino M , Monda A , Scozia G , Pietrangelo B , Attrotto M , Apud J A , Chen Q , Mattay V S , Rampino A , Caforio G , Weinberger D R , Blasi G , Bertolino A
Published: January 2017

Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes. Next, we identified non-coding single-nucleotide polymorphisms (SNPs) associated with co-expression of this pathway. These SNPs were associated with regulatory genetic loci in the dorsolateral prefrontal cortex (P<0.05). We summarized their compound effect on co-expression into a Polygenic Co-expression Index (PCI), which predicted DRD2 pathway co-expression in both mRNA data sets (all P<0.05). We associated the PCI with brain activity during WM performance in two independent samples of healthy individuals (total N=368) and 29 patients with SCZ who performed the n-back task. Greater predicted DRD2 pathway prefrontal co-expression was associated with greater prefrontal activity and longer WM reaction times (all corrected P<0.05), thus indicating inefficient WM processing. Blind prediction of treatment response to antipsychotics in two independent samples of patients with SCZ suggested better clinical course of patientswith greater PCI (total N=87; P<0.05). The findings on this DRD2 co-expression pathway are a proof of concept that gene co-expression can parse SCZ risk genes into biological pathways associated with intermediate phenotypes as well as with clinically meaningful information.
High-throughput screening of triplex DNA binders from complicated samples by 96-well pate format in conjunction with peak area-fading UHPLC-Orbitrap MS
Authors: Yang Hongmei , Yao Wenbin , Wang Yihan , Shi Lei , Su Rui , Wan Debin , Xu Niusheng , Lian Wenhui , Chen Changbao , Liu Shuying
Published: January 2017

Screening triplex DNA binders from complicated samples in a high-throughput fashion with good reproducibility without the requirement of an extra releasing step.
Sensor array optimization and discrimination of apple juices according to variety by an electronic nose
Authors: Wu Hao , Yue TianLi , Xu Zhijiao , Zhang Chen
Published: January 2017

An electronic nose (PEN3) containing 10 metal oxide semiconductor type chemical sensors was used to discriminate between eight varieties of apple juice.
Photoinduced electron transfer in layer-by-layer thin solid films containing cobalt oxide nanosheets, porphyrin, and methyl viologen
Authors: Sasai R. , Kato Y. , Soontornchaiyakul W. , Usami H. , Masumori A. , Norimatsu W. , Fujimura T. , Takagi S.
Published: January 2017

We succeeded in preparing the layer-by-layer thin solid film with cobaltate nanosheet (CoNS)/porphyrin (TMPyP)/CoNS/methyl viologen (MV)/CoNS sequence, and found that the photoinduced electron transfer from TMPyP to MV bound to CoNS with long life time could be observed.
Synthesis and SMM behaviour of trinuclear versus dinuclear 3d–5f uranyl(v)–cobalt(ii) cation–cation complexes
Authors: Chatelain Lucile , Tuna Floriana , Pécaut Jacques , Mazzanti Marinella
Published: January 2017

Trinuclear versus dinuclear heterodimetallic UVO2+⋯Co2+ complexes were selectively assembled via a cation–cation interaction by tuning the ligand. The trimeric complex, exhibits magnetic exchange and slow relaxation providing the first example of a U–Co exchange-coupled SMM.
Sonogashira cross-coupling reactions of 3,5-dibromo-2,6-dichloropyridine
Authors: Reimann Sebastian , Ehlers Peter , Ohlendorf Lars , Langer Peter
Published: January 2017

Polyalkynylated pyridines were obtained by chemoselective Sonogashira reactions which are not accessible by other methods.