bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared genetic influences do not explain the association between parent–offspring relationship quality and offspring internalizing problems: results from a Children-of-Twins study
Authors: Hannigan L. J. , Rijsdijk F. V. , Ganiban J. M. , Reiss D. , Spotts E. L. , Neiderhiser J. M. , Lichtenstein P. , McAdams T. A. , Eley T. C.
Published: July 2017

Background

Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associations may be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanism may explain links between them. Here we aim to quantify the relative importance of passive geneticv.social mechanisms in the intergenerational association between parent–offspring relationship quality and offspring internalizing problems in adolescence.

Methods

We used a Children-of-Twins (CoT) design with data from the parent-based Twin and Offspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspring mean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent–offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples.

Results

A social transmission mechanism explained the intergenerational association [r= 0.21 (0.16–0.25)] in our best-fitting model. A passive genetic transmission pathway was not found to be significant, indicating that parental genetic influences on parent–offspring relationship quality and offspring genetic influences on their internalizing problems were non-overlapping.

Conclusion

These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results from genetically informative studies of parenting-related effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology.
The dynamic interaction between lexical and contextual frequency: A case study of (ING)
Authors: Forrest Jon
Published: July 2017

To identify how contextual usage frequency and lexical frequency interact when controlling for traditional linguistic constraints, this study analyzes the effect of frequency on (ING), taking into account a word's frequent context of occurrence. The data consist of 13,167 tokens of (ING) from interviews with 132 speakers conducted in Raleigh, North Carolina. Results from mixed-effect logistic regression show a strong effect of frequency on the realization of (ING), and this effect interacts with phonological context of occurrence. Frequent occurrence in environments that favor-inamplify the effect of lexical frequency; conversely, frequent occurrence in environments that favor–ingdampen the effect of overall frequency. Frequency also interacts with year of birth, showing an entrenchment of high-frequency words, lagging behind the community change toward the–ingvariant in apparent time. Overall, these findings support the usage-based position of frequency effects as the result of a dynamic interplay between context of use and cognitive systems.
Benefits of Manometer in Non-Invasive Ventilatory Support
Authors: Lacerda Rodrigo Silva , de Lima Fernando Cesar Anastácio , Bastos Leonardo Pereira , Fardin Vinco Anderson , Schneider Felipe Britto Azevedo , Luduvico Coelho Yves , Fernandes Heitor Gomes Costa , Bacalhau João Marcus Ramos , Bermudes Igor Matheus Simonelli , da Silva Claudinei Ferreira , da Silva Luiza Paterlini , Pezato Rogério
Published: July 2017

Introduction

Effective ventilation during cardiopulmonary resuscitation (CPR) is essential to reduce morbidity and mortality rates in cardiac arrest. Hyperventilation during CPR reduces the efficiency of compressions and coronary perfusion.

Problem

How could ventilation in CPR be optimized? The objective of this study was to evaluate non-invasive ventilator support using different devices.

Methods

The study compares the regularity and intensity of non-invasive ventilation during simulated, conventional CPR and ventilatory support using three distinct ventilation devices: a standard manual resuscitator, with and without airway pressure manometer, and an automatic transport ventilator. Student’s t-test was used to evaluate statistical differences between groups. P values <.05 were regarded as significant.

Results

Peak inspiratory pressure during ventilatory support and CPR was significantly increased in the group with manual resuscitator without manometer when compared with the manual resuscitator with manometer support (MS) group or automatic ventilator (AV) group.

Conclusion

The study recommends for ventilatory support the use of a manual resuscitator equipped with MS or AVs, due to the risk of reduction in coronary perfusion pressure and iatrogenic thoracic injury during hyperventilation found using manual resuscitator without manometer.

LacerdaRS, de LimaFCA, BastosLP, VincoAF, SchneiderFBA, CoelhoYL, FernandesHGC, BacalhauJMR, BermudesIMS, da SilvaCF, da SilvaLP, PezatoR. Benefits of manometer in non-invasive ventilatory support. Prehosp Disaster Med. 2017;32(6):615–620.
TECHNOLOGY SHOCKS AND BUSINESS CYCLES IN INDIA
Authors: Banerjee Shesadri , Basu Parantap
Published: July 2017

In this paper, we develop a small open economy New Keynesian dynamic stochastic general equilibrium (DSGE) model to understand the relative importance of two key technology shocks, Hicks neutral total factor productivity (TFP) shock and investment specific technology (IST) shock for an emerging market economy like India. In addition to these two shocks, our model includes three demand side shocks such as fiscal spending, home interest rate, and foreign interest rate. Using a Bayesian approach, we estimate our DSGE model with Indian annual data for key macroeconomic variables over the period of 1971–2010, and for subsamples of pre-liberalization (1971–1990) and post-liberalization (1991–2010) periods. Our study reveals three main results. First, output correlates positively with TFP, but negatively with IST. Second, TFP and IST shocks are the first and the second most important contributors to aggregate fluctuations in India. In contrast, the demand side disturbances play a limited role. Third, although TFP plays a major role in determining aggregate fluctuations, its importance vis-à-vis IST has declined during the post liberalization era. We find that structural shifts of nominal friction and relative home bias for consumption to investment in the post-liberalization period can account for the rising importance of the IST shocks in India.
An optimal multi-layer reinsurance policy under conditional tail expectation
Authors: Najafabadi Amir T. Payandeh , Bazaz Ali Panahi
Published: July 2017

An usual reinsurance policy for insurance companies admits one or two layers of the payment deductions. Under optimality criterion of minimising the Conditional Tail Expectation (CTE) risk measure of the insurer’s total risk, this article generalises an optimal stop-loss reinsurance policy to an optimal multi-layer reinsurance policy. To achieve such optimal multi-layer reinsurance policy, this article starts from a given optimal stop-loss reinsurance policy f(⋅). In the first step, it cuts down the interval [0, ∞) into intervals [0, M1) and [M1, ∞). By shifting the origin of Cartesian coordinate system to (M1, f(M1)), and showing that under the CTE criteria
$$f\left( x \right)I_{{[0,M_{{\rm 1}} )}} \left( x \right){\plus}\left( {f\left( {M_{{\rm 1}} } \right){\plus}f\left( {x{\minus}M_{{\rm 1}} } \right)} \right)I_{{[M_{{\rm 1}} ,{\rm }\infty)}} \left( x \right)$$
is, again, an optimal policy. This extension procedure can be repeated to obtain an optimal k-layer reinsurance policy. Finally, unknown parameters of the optimal multi-layer reinsurance policy are estimated using some additional appropriate criteria. Three simulation-based studies have been conducted to demonstrate: (1) the practical applications of our findings and (2) how one may employ other appropriate criteria to estimate unknown parameters of an optimal multi-layer contract. The multi-layer reinsurance policy, similar to the original stop-loss reinsurance policy is optimal, in a same sense. Moreover, it has some other optimal criteria which the original policy does not have. Under optimality criterion of minimising a general translative and monotone risk measure ρ(⋅) of either the insurer’s total risk or both the insurer’s and the reinsurer’s total risks, this article (in its discussion) also extends a given optimal reinsurance contract f(⋅) to a multi-layer and continuous reinsurance policy.
Presentation of the Coding and Assessment System for Narratives of Trauma (CASNOT): Application in Spanish Battered Women and Preliminary Analyses
Authors: Fernández-Lansac Violeta , Crespo María
Published: July 2017

This study introduces a new coding system, the Coding and Assessment System for Narratives of Trauma (CASNOT), to analyse several language domains in narratives of autobiographical memories, especially in trauma narratives. The development of the coding system is described. It was applied to assess positive and traumatic/negative narratives in 50 battered women (trauma-exposed group) and 50 nontrauma-exposed women (control group). Three blind raters coded each narrative. Inter-rater reliability analyses were conducted for the CASNOT language categories (multirater Kfree coefficients) and dimensions (intraclass correlation coefficients). High levels of inter-rater agreement were found for most of the language domains. Categories that did not reach the expected reliability were mainly those related to cognitive processes, which reflects difficulties in operationalizing constructs such as lack of control or helplessness, control or planning, and rationalization or memory elaboration. Applications and limitations of the CASNOT are discussed to enhance narrative measures for autobiographical memories.
Zielgerichtete gynäko-onkologische Therapien – häufige Nebenwirkungen und deren Management
Authors: Samartzis Eleftherios Pierre , Fink Daniel
Published: July 2017

Zusammenfassung. Zusammenfassung: Eine gute interdisziplinäre Zusammenarbeit ist in der Behandlung von Patientinnen mit Brustkrebs oder gynäkologisch-onkologischen Tumoren entscheidend. Meistens finden parallel zur onkologischen Behandlung regelmässige Konsultationen beim Allgemeinpraktiker und niedergelassenen Gynäkologen statt. Die Erkennung und frühe Behandlung potenzieller Nebenwirkungen von zielgerichteten onkologischen Therapien ist daher in der allgemeinen Praxis sehr wichtig. In diesem Artikel soll ein Überblick über die wichtigsten Nebenwirkungen zielgerichteter onkologischer Therapien in der gynäkologischen Onkologie und Brustkrebsbehandlung und deren Management gegeben werden.
A TBX5 3′UTR variant increases the risk of congenital heart disease in the Han Chinese population
Authors: Wang Feng , Liu Dong , Zhang Ran-Ran , Yu Li-Wei , Zhao Jian-Yuan , Yang Xue-Yan , Jiang Song-Shan , Ma Duan , Qiao Bin , Zhang Feng , Jin Li , Gui Yong-Hao , Wang Hong-Yan
Published: July 2017

TBX5 is a vital transcription factor involved in cardiac development in a dosage-dependent manner. But little is known about the potential association of TBX5 3′ untranslated region (UTR) variations with congenital cardiac malformations. This study aimed to investigate the relationship between TBX5 3′UTR variants and risk for congenital heart disease (CHD) susceptibility in two Han Chinese populations, and to reveal its molecular mechanism. The relationship between TBX5 3′UTR variants and CHD susceptibility was examined in 1 177 CHD patients and 990 healthy controls in two independent case–control studies. Variant rs6489956 C>T was found to be associated with increased CHD susceptibility in both cohorts. The combined CHD risk for the CT and TT genotype carriers was 1.83 times higher than that of CC genotype, while the risk for CT or TT genotype was 1.94 times and 2.31 times higher than that of CC carriers, respectively. Quantitative real-time PCR and western blot analysis showed that T allele carriers exhibited reduced TBX5 mRNA and protein levels in CHDs tissues. Compared with C allele, T allele showed increased binding affinity to miR-9 and miR-30a in both luciferase assays and surface plasmon resonance analysis. Functional analysis confirmed that miR-9 and miR-30a downregulated TBX5 expression at the transcriptional and translational levels, respectively. The assays in zebrafish model were in support of the interaction of miR-9/30a and TBX5 3′UTR (C and T allele). We concluded that TBX5 3′UTR variant rs6489956 increased susceptibility of CHD in the Han Chinese population because it changes the binding affinity of two target miRNAs that specifically mediate TBX5 expression.
Spiraling pathways of global deep waters to the surface of the Southern Ocean
Authors: Tamsitt Veronica , Drake Henri F. , Morrison Adele K. , Talley Lynne D. , Dufour Carolina O. , Gray Alison R. , Griffies Stephen M. , Mazloff Matthew R. , Sarmiento Jorge L. , Wang Jinbo , Weijer Wilbert
Published: July 2017

Upwelling of global deep waters to the sea surface in the Southern Ocean closes the global overturning circulation and is fundamentally important for oceanic uptake of carbon and heat, nutrient resupply for sustaining oceanic biological production, and the melt rate of ice shelves. However, the exact pathways and role of topography in Southern Ocean upwelling remain largely unknown. Here we show detailed upwelling pathways in three dimensions, using hydrographic observations and particle tracking in high-resolution models. The analysis reveals that the northern-sourced deep waters enter the Antarctic Circumpolar Current via southward flow along the boundaries of the three ocean basins, before spiraling southeastward and upward through the Antarctic Circumpolar Current. Upwelling is greatly enhanced at five major topographic features, associated with vigorous mesoscale eddy activity. Deep water reaches the upper ocean predominantly south of the Antarctic Circumpolar Current, with a spatially nonuniform distribution. The timescale for half of the deep water to upwell from 30° S to the mixed layer is ~60–90 years.
Ionic liquid accelerates the crystallization of Zr-based metal–organic frameworks
Authors: Sang Xinxin , Zhang Jianling , Xiang Junfeng , Cui Jie , Zheng Lirong , Zhang Jing , Wu Zhonghua , Li Zhihong , Mo Guang , Xu Yuan , Song Jinliang , Liu Chengcheng , Tan Xiuniang , Luo Tian , Zhang Bingxing , Han Buxing
Published: July 2017

The Zr-based metal–organic frameworks are generally prepared by solvothermal procedure. To overcome the slow kinetics of nucleation and crystallization of Zr-based metal–organic frameworks is of great interest and challenging. Here, we find that an ionic liquid as solvent can significantly accelerate the formation of Zr-based metal–organic frameworks at room temperature. For example, the reaction time is shortened to 0.5 h in 1-hexyl-3-methylimidazolium chloride for Zr-based metal–organic framework formation, while that in the conventional solvent N,N-dimethylformamide needs at least 120 h. The reaction mechanism was investigated in situ by 1H nuclear magnetic resonance, spectroscopy synchrotron small angle X-ray scattering and X-ray absorption fine structure. This rapid, low-energy, and facile route produces Zr-based metal–organic framework nanoparticles with small particle size, missing-linker defects and large surface area, which can be used as heterogeneous catalysts for Meerwein–Ponndorf–Verley reaction.
Antiferromagnetic domain wall as spin wave polarizer and retarder
Authors: Lan Jin , Yu Weichao , Xiao Jiang
Published: July 2017

As a collective quasiparticle excitation of the magnetic order in magnetic materials, spin wave, or magnon when quantized, can propagate in both conducting and insulating materials. Like the manipulation of its optical counterpart, the ability to manipulate spin wave polarization is not only important but also fundamental for magnonics. With only one type of magnetic lattice, ferromagnets can only accommodate the right-handed circularly polarized spin wave modes, which leaves no freedom for polarization manipulation. In contrast, antiferromagnets, with two opposite magnetic sublattices, have both left and right-circular polarizations, and all linear and elliptical polarizations. Here we demonstrate theoretically and confirm by micromagnetic simulations that, in the presence of Dzyaloshinskii-Moriya interaction, an antiferromagnetic domain wall acts naturally as a spin wave polarizer or a spin wave retarder (waveplate). Our findings provide extremely simple yet flexible routes toward magnonic information processing by harnessing the polarization degree of freedom of spin wave.
Cloaking of Thermoelectric Transport
Authors: Stedman Troy , Woods Lilia M.
Published: July 2017

The ability to control electromagnetic fields, heat currents, electric currents, and other physical phenomena by coordinate transformation methods has resulted in novel functionalities, such as cloaking, field rotations, and concentration effects. Transformation optics, as the underlying mathematical tool, has proven to be a versatile approach to achieve such unusual outcomes relying on materials with highly anisotropic and inhomogeneous properties. Most applications and designs thus far have been limited to functionalities within a single physical domain. Here we present transformation optics applied to thermoelectric phenomena, where thermal and electric flows are coupled via the Seebeck coefficient. Using laminates, we describe a thermoelectric cloak capable of hiding objects from thermoelectric flow. Our calculations show that such a cloak does not depend on the particular boundary conditions and can also operate in different single domain regimes. These proof-of-principle results constitute a significant step forward towards finding unexplored ways to control and manipulate coupled transport.
Inhibition of AKT1 signaling promotes invasion and metastasis of non-small cell lung cancer cells with K-RAS or EGFR mutations
Authors: Rao Guanhua , Pierobon Mariaelena , Kim In-Kyu , Hsu Wei-Hsun , Deng Jianghong , Moon Yong-Wha , Petricoin Emanuel F. , Zhang Yu-Wen , Wang Yisong , Giaccone Giuseppe
Published: July 2017

Accumulating evidence supports a role of the PI3K-AKT pathway in the regulation of cell motility, invasion and metastasis. AKT activation is known to promote metastasis, however under certain circumstances, it also shows an inhibitory activity on metastatic processes, and the cause of such conflicting results is largely unclear. Here we found that AKT1 is an important regulator of metastasis and down-regulation of its activity is associated with increased metastatic potential of A549 cells. Inhibition of AKT1 enhanced migration and invasion in KRAS- or EGFR-mutant non-small cell lung cancer (NSCLC) cells. The allosteric AKT inhibitor MK-2206 promoted metastasis of KRAS-mutated A549 cells in vivo. We next identified that the phosphorylation of Myristoylated alanine-rich C-kinase substrate (MARCKS) and LAMC2 protein level were increased with AKT1 inhibition, and MARCKS or LAMC2 knockdown abrogated migration and invasion induced by AKT1 inhibition. This study unravels an anti-metastatic role of AKT1 in the NSCLC cells with KRAS or EGFR mutations, and establishes an AKT1-MARCKS-LAMC2 feedback loop in this regulation.
NOD2 gene variants confer risk for secondary sclerosing cholangitis in critically ill patients
Authors: Jüngst Christoph , Stadlbauer Vanessa , Reichert Matthias C. , Zimmer Vincent , Weber Susanne N. , Ofner-Ziegenfuß Lisa , Voigtländer Torsten , Spindelböck Walter , Fickert Peter , Kirchner Gabriele I. , Lammert Frank , Lankisch Tim O. , Krawczyk Marcin
Published: July 2017

Sclerosing cholangitis in critically ill patients (SC-CIP) is a progressive cholestatic disease of unknown aetiology characterized by chronic biliary infections. Hence we hypothesized that common NOD2 (nucleotide-binding oligomerisation domain containing 2) gene variants, known risk factors for Crohn’s disease and bacterial translocation in liver cirrhosis, increase the odds of developing SC-CIP. Screening of 4,641 endoscopic retrograde cholangiography procedures identified 17 patients with SC-CIP, who were then genotyped for the three common NOD2 mutations (Cohort 1, discovery cohort). To validate the association, we subsequently tested these NOD2 variants in 29 patients from SC-CIP cohorts of three additional medical centers (Cohort 2, replication cohort). In Cohort 1, the NOD2 variants were present in 5 of 17 SC-CIP patients (29.4%), which is twice the frequency of the general population. These results were replicated in Cohort 2 with 8 patients (27.6%) showing NOD2 mutations. In contrast, polymorphisms of hepatocanalicular transporter genes did not have major impact on SC-CIP risk. This first study on genetic susceptibility in SC-CIP patients shows an extraordinary high frequency of NOD2 variation, pointing to a critical role of inherited impaired anti-bacterial defense in the development of this devastating biliary disease.
Monolithic mode-selective few-mode multicore fiber multiplexers
Authors: Riesen Nicolas , Gross Simon , Love John D. , Sasaki Yusuke , Withford Michael J.
Published: July 2017

With the capacity limits of standard single-mode optical fiber fast approaching, new technologies such as space-division multiplexing are required to avoid an Internet capacity crunch. Few-mode multicore fiber (FM-MCF) could allow for a two orders of magnitude increase in capacity by using the individual spatial modes in the different cores as unique data channels. We report the realization of a monolithic mode-selective few-mode multicore fiber multiplexer capable of addressing the individual modes of such a fiber. These compact multiplexers operate across the S + C + L telecommunications bands and were inscribed into a photonic chip using ultrafast laser inscription. They allow for the simultaneous multiplexing of the LP01, LP11a and LP11b modes of all cores in a 3-mode, 4-core fiber with excellent mode extinction ratios and low insertion losses. The devices are scalable to more modes and cores and therefore could represent an enabling technology for practical ultra-high capacity dense space-division multiplexing.
Metacognitive Deficiency in a Perceptual but Not a Memory Task in Methadone Maintenance Patients
Authors: Sadeghi Saeedeh , Ekhtiari Hamed , Bahrami Bahador , Ahmadabadi Majid Nili
Published: July 2017

Drug addiction has been associated with lack of insight into one’s own abilities. However, the scope of metacognition impairment among drug users in general and opiate dependent individuals in particular is not fully understood. Investigating the impairments of metacognitive ability in Substance Dependent Individuals (SDIs) in different cognitive tasks could contribute to the ongoing debate over whether metacognition has domain-general or domain-specific neural substrates. We compared metacognitive self-monitoring ability of a group of SDIs during methadone maintenance treatment (n = 23) with a control group (n = 24) in a memory and a visual perceptual task. Post decision self judgements of probability of correct choice were obtained through trial by trial confidence ratings and were used to compute metacognitive ability. Results showed that despite comparable first order performance in the perceptual task, SDIs had lower perceptual metacognition than the control group. However, although SDIs had poorer memory performance, their metacognitive judgements in the memory task were as accurate as the control group. While it is commonly believed that addiction causes pervasive impairment in cognitive functions, including metacognitive ability, we observed that the impairment was only significant in one specific task, the perceptual task, but not in the memory task.
Locus of Adhesion and Autoaggregation (LAA), a pathogenicity island present in emerging Shiga Toxin–producing Escherichia coli strains
Authors: Montero David A. , Velasco Juliana , Del Canto Felipe , Puente Jose L. , Padola Nora L. , Rasko David A. , Farfán Mauricio , Salazar Juan C. , Vidal Roberto
Published: July 2017

Shiga Toxin-producing Escherichia coli (STEC) are a group of foodborne pathogens associated with diarrhea, dysentery, hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). Shiga toxins are the major virulence factor of these pathogens, however adhesion and colonization to the human intestine is required for STEC pathogenesis. A subset of STEC strains carry the Locus of Enterocyte Effacement (LEE) pathogenicity island (PAI), which encodes genes that mediate the colonization of the human intestine. While LEE-positive STEC strains have traditionally been associated with human disease, the burden of disease caused by STEC strains that lacks LEE (LEE-negative) has increased recently in several countries; however, in the absence of LEE, the molecular pathogenic mechanisms by STEC strains are unknown. Here we report a 86-kb mosaic PAI composed of four modules that encode 80 genes, including novel and known virulence factors associated with adherence and autoaggregation. Therefore, we named this PAI as Locus of Adhesion and Autoaggregation (LAA). Phylogenomic analysis using whole-genome sequences of STEC strains available in the NCBI database indicates that LAA PAI is exclusively present in a subset of emerging LEE-negative STEC strains, including strains isolated from HC and HUS cases. We suggest that the acquisition of this PAI is a recent evolutionary event, which may contribute to the emergence of these STEC.
Intracoronary Imaging, Cholesterol Efflux, and Transcriptomics after Intensive Statin Treatment in Diabetes
Authors: Chamaria Surbhi , Johnson Kipp W. , Vengrenyuk Yuliya , Baber Usman , Shameer Khader , Divaraniya Aparna A. , Glicksberg Benjamin S. , Li Li , Bhatheja Samit , Moreno Pedro , Maehara Akiko , Mehran Roxana , Dudley Joel T. , Narula Jagat , Sharma Samin K. , Kini Annapoorna S.
Published: July 2017

Residual atherothrombotic risk remains higher in patients with versus without diabetes mellitus (DM) despite statin therapy. The underlying mechanisms are unclear. This is a retrospective post-hoc analysis of the YELLOW II trial, comparing patients with and without DM (non-DM) who received rosuvastatin 40 mg for 8–12 weeks and underwent intracoronary multimodality imaging of an obstructive nonculprit lesion, before and after therapy. In addition, blood samples were drawn to assess cholesterol efflux capacity (CEC) and changes in gene expression in peripheral blood mononuclear cells (PBMC). There was a significant reduction in low density lipoprotein-cholesterol (LDL-C), an increase in CEC and beneficial changes in plaque morphology including increase in fibrous cap thickness and decrease in the prevalence of thin cap fibro-atheroma by optical coherence tomography in DM and non-DM patients. While differential gene expression analysis did not demonstrate differences in PBMC transcriptome between the two groups on the single-gene level, weighted gene coexpression network analysis revealed two modules of coexpressed genes associated with DM, Collagen Module and Platelet Module, related to collagen catabolism and platelet function respectively. Bayesian network analysis revealed key driver genes within these modules. These transcriptomic findings might provide potential mechanisms responsible for the higher cardiovascular risk in DM patients.
Calcium Ion Induced Structural Changes Promote Dimerization of Secretagogin, Which Is Required for Its Insulin Secretory Function
Authors: Lee Jae-Jin , Yang Seo-Yun , Park Jimin , Ferrell James E. , Shin Dong-Hae , Lee Kong-Joo
Published: July 2017

Secretagogin (SCGN), a hexa EF-hand calcium binding protein, plays key roles in insulin secretion in pancreatic β-cells. It is not yet understood how the binding of Ca2+ to human SCGN (hSCGN) promotes secretion. Here we have addressed this question, using mass spectrometry combined with a disulfide searching algorithm DBond. We found that the binding of Ca2+ to hSCGN promotes the dimerization of hSCGN via the formation of a Cys193-Cys193 disulfide bond. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) and molecular dynamics studies revealed that Ca2+ binding to the EF-hands of hSCGN induces significant structural changes that affect the solvent exposure of N-terminal region, and hence the redox sensitivity of the Cys193 residue. These redox sensitivity changes were confirmed using biotinylated methyl-3-nitro-4-(piperidin-1-ylsulfonyl) benzoate (NPSB-B), a chemical probe that specifically labels reactive cysteine sulfhydryls. Furthermore, we found that wild type hSCGN overexpression promotes insulin secretion in pancreatic β cells, while C193S-hSCGN inhibits it. These findings suggest that insulin secretion in pancreatic cells is regulated by Ca2+ and ROS signaling through Ca2+-induced structural changes promoting dimerization of hSCGN.
Pair distribution function analysis of sulfide glassy electrolytes for all-solid-state batteries: Understanding the improvement of ionic conductivity under annealing condition
Authors: Shiotani Shinya , Ohara Koji , Tsukasaki Hirofumi , Mori Shigeo , Kanno Ryoji
Published: July 2017

In general, the ionic conductivity of sulfide glasses decreases with their crystallization, although it increases for a few sulphide glasses owing to the crystallization of a highly conductive new phase (e.g., Li7P3S11: 70Li2S-30P2S5). We found that the ionic conductivity of 75Li2S-25P2S5 sulfide glass, which consists of glassy and crystalline phases, is improved by optimizing the conditions of the heat treatment, i.e., annealing. A different mechanism of high ionic conductivity from the conventional mechanism is expected in the glassy phase. Here, we report the glassy structure of 75Li2S-25P2S5 immediately before the crystallization by using the differential pair distribution function (d-PDF) analysis of high-energy X-ray diffraction. Even though the ionic conductivity increases during the optimum annealing, the d-PDF analysis indicated that the glassy structure undergoes no structural change in the sulfide glass-ceramic electrolyte at a crystallinity of 33.1%. We observed the formation of a nanocrystalline phase in the X-ray and electron diffraction patterns before the crystallization, which means that Bragg peaks were deformed. Thus, the ionic conductivity in the mixture of glassy and crystalline phases is improved by the coexistence of the nanocrystalline phase.
Bmal1 regulates inflammatory responses in macrophages by modulating enhancer RNA transcription
Authors: Oishi Yumiko , Hayashi Shinichiro , Isagawa Takayuki , Oshima Motohiko , Iwama Atsushi , Shimba Shigeki , Okamura Hitoshi , Manabe Ichiro
Published: July 2017

Bmal1 (encoded by Arntl gene) is a core circadian clock gene that regulates various genes involved in circadian rhythm. Although Bmal1 is expressed rhythmically in macrophages, the role of Bmal1 in the regulation of their cellular function remains insufficiently understood. Here, we report that Bmal1 regulates time-dependent inflammatory responses following Toll-like receptor 4 (TLR4) activation by modulating enhancer activity. Global transcriptome analysis indicated that deletion of Arntl perturbed the time-dependent inflammatory responses elicited by TLR4 activation by Kdo2-lipid A (KLA). Although the recruitment of NF-κB p65 was unaffected, the acetylation status of lysine 27 of histone 3, which correlates positively with enhancer activity, was globally increased at PU.1-containing enhancers in Arntl−/− macrophages as compared to wild-type cells. Expression of Nr1d1 and Nr1d2, encoding RevErb transcription factors, which repress enhancer RNA expression, was significantly decreased in Arntl−/− macrophages. Moreover, the level of H3K27 acetylation was increased by Arntl deletion at RevErb-dependent eRNA-expressing enhancers. These results suggest that Bmal1 controls KLA-responsive enhancers, in part by regulating RevErb-directed eRNA transcription. Taken together, the results of this study show that the clock transcription factor network containing Bmal1 controls the inflammatory responses of macrophages by regulating the epigenetic states of enhancers.
Carbon black as an alternative cathode material for electrical energy recovery and transfer in a microbial battery
Authors: Zhang Xueqin , Guo Kun , Shen Dongsheng , Feng Huajun , Wang Meizhen , Zhou Yuyang , Jia Yufeng , Liang Yuxiang , Zhou Mengjiao
Published: July 2017

Rather than the conventional concept of viewing conductive carbon black (CB) to be chemically inert in microbial electrochemical cells (MECs), here we confirmed the redox activity of CB for its feasibility as an electron sink in the microbial battery (MB). Acting as the cathode of a MB, the solid-state CB electrode showed the highest electron capacity equivalent of 18.58 ± 0.46 C/g for the unsintered one and the lowest capacity of 2.29 ± 0.48 C/g for the one sintered under 100% N2 atmosphere. The capacity vibrations of CBs were strongly in coincidence with the abundances of C=O moiety caused by different pretreatments and it implied one plausible mechanism based on CB’s surface functionality for its electron capturing. Once subjected to electron saturation, CB could be completely regenerated by different strategies in terms of electrochemical discharging or donating electrons to biologically-catalyzed nitrate reduction. Surface characterization also revealed that CB’s regeneration fully depended on the reversible shift of C=O moiety, further confirming the functionality-based mechanism for CB’s feasibility as the role of MB’s cathode. Moreover, resilience tests demonstrated that CB cathode was robust for the multi-cycles charging-discharging operations. These results imply that CB is a promising alternative material for the solid-state cathode in MBs.
Lagrangian dynamical geography of the Gulf of Mexico
Authors: Miron P. , Beron-Vera F. J. , Olascoaga M. J. , Sheinbaum J. , Pérez-Brunius P. , Froyland G.
Published: July 2017

We construct a Markov-chain representation of the surface-ocean Lagrangian dynamics in a region occupied by the Gulf of Mexico (GoM) and adjacent portions of the Caribbean Sea and North Atlantic using satellite-tracked drifter trajectory data, the largest collection so far considered. From the analysis of the eigenvectors of the transition matrix associated with the chain, we identify almost-invariant attracting sets and their basins of attraction. With this information we decompose the GoM’s geography into weakly dynamically interacting provinces, which constrain the connectivity between distant locations within the GoM. Offshore oil exploration, oil spill contingency planning, and fish larval connectivity assessment are among the many activities that can benefit from the dynamical information carried in the geography constructed here.
Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice
Authors: Horii Yasuyuki , Nagasawa Tatsuhiro , Sakakibara Hiroyuki , Takahashi Aki , Tanave Akira , Matsumoto Yuki , Nagayama Hiromichi , Yoshimi Kazuto , Yasuda Michiko T. , Shimoi Kayoko , Koide Tsuyoshi
Published: July 2017

Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.
In silico analyses of conservational, functional and phylogenetic distribution of the LuxI and LuxR homologs in Gram-positive bacteria
Authors: Rajput Akanksha , Kumar Manoj
Published: July 2017

LuxI and LuxR are key factors that drive quorum sensing (QS) in bacteria through secretion and perception of the signaling molecules e.g. N-Acyl homoserine lactones (AHLs). The role of these proteins is well established in Gram-negative bacteria for intercellular communication but remain under-explored in Gram-positive bacteria where QS peptides are majorly responsible for cell-to-cell communication. Therefore, in the present study, we explored conservation, potential function, topological arrangements and evolutionarily aspects of these proteins in Gram-positive bacteria. Putative LuxI/LuxR containing proteins were retrieved using the domain-based strategy from InterPro v62.0 meta-database. Conservational analyses via multiple sequence alignment and domain showed that these are well conserved in Gram-positive bacteria and possess relatedness with Gram-negative bacteria. Further, Gene ontology and ligand-based functional annotation explain their active involvement in signal transduction mechanism via QS signaling molecules. Moreover, Phylogenetic analyses (LuxI, LuxR, LuxI + LuxR and 16s rRNA) revealed horizontal gene transfer events with significant statistical support among Gram-positive and Gram-negative bacteria. This in-silico study offers a detailed overview of potential LuxI/LuxR distribution in Gram-positive bacteria (mainly Firmicutes and Actinobacteria) and their functional role in QS. It would further help in understanding the extent of interspecies communications between Gram-positive and Gram-negative bacteria through QS signaling molecules.
Antimicrobial spray nanocoating of supramolecular Fe(III)-tannic acid metal-organic coordination complex: applications to shoe insoles and fruits
Authors: Park Ji Hun , Choi Sohee , Moon Hee Chul , Seo Hyelin , Kim Ji Yup , Hong Seok-Pyo , Lee Bong Soo , Kang Eunhye , Lee Jinho , Ryu Dong Hun , Choi Insung S.
Published: July 2017

Numerous coating strategies are available to control the surface properties and confer new properties to substrates for applications in energy, environment, biosystems, etc., but most have the intrinsic limitations in the practical setting: (1) highly specific interactions between coating materials and target surfaces are required for stable and durable coating; (2) the coating of bulk substrates, such as fruits, is time-consuming or is not achievable in the conventional solution-based coating. In this respect, material-independent and rapid coating strategies are highly demanded. We demonstrate spray-assisted nanocoating of supramolecular metal-organic complexes of tannic acid and ferric ions. The spray coating developed is material-independent and extremely rapid (<5 sec), allowing for coating of commodity goods, such as shoe insoles and fruits, in the controlled fashion. For example, the spray-coated mandarin oranges and strawberries show significantly prolonged post-harvest shelf-life, suggesting practical potential in edible coating of perishable produce.
Bacteriophages as potential new mammalian pathogens
Authors: Tetz George V. , Ruggles Kelly V. , Zhou Hua , Heguy Adriana , Tsirigos Aristotelis , Tetz Victor
Published: July 2017

Increased intestinal permeability and translocation of gut bacteria trigger various polyaetiological diseases associated with chronic inflammation and underlie a variety of poorly treatable pathologies. Previous studies have established a primary role of the microbiota composition and intestinal permeability in such pathologies. Using a rat model, we examined the effects of exposure to a bacteriophage cocktail on intestinal permeability and relative abundance of taxonomic units in the gut bacterial community. There was an increase in markers of impaired gut permeability, such as the lactulose/mannitol ratio, plasma endotoxin concentrations, and serum levels of inflammation-related cytokines, following the bacteriophage challenge. We observed significant differences in the alpha diversity of faecal bacterial species and found that richness and diversity index values increased following the bacteriophage challenge. There was a reduction in the abundance of Blautia, Catenibacterium, Lactobacillus, and Faecalibacterium species and an increase in Butyrivibrio, Oscillospira and Ruminococcus after bacteriophage administration. These findings provide novel insights into the role of bacteriophages as potentially pathogenic for mammals and their possible implication in the development of diseases associated with increased intestinal permeability.
Order-disorder transition in active nematic: A lattice model study
Authors: Das Rakesh , Kumar Manoranjan , Mishra Shradha
Published: July 2017

We introduce a lattice model for active nematic composed of self-propelled apolar particles, study its different ordering states in the density-temperature parameter space, and compare with the corresponding equilibrium model. The active particles interact with their neighbours within the framework of the Lebwohl-Lasher model, and move anisotropically along their orientation to an unoccupied nearest neighbour lattice site. An interplay of the activity, thermal fluctuations and density gives rise distinct states in the system. For a fixed temperature, the active nematic shows a disordered isotropic state, a locally ordered inhomogeneous mixed state, and bistability between the inhomogeneous mixed and a homogeneous globally ordered state in different density regime. In the low temperature regime, the isotropic to the inhomogeneous mixed state transition occurs with a jump in the order parameter at a density less than the corresponding equilibrium disorder-order transition density. Our analytical calculations justify the shift in the transition density and the jump in the order parameter. We construct the phase diagram of the active nematic in the density-temperature plane.
Pdx1-Cre-driven conditional gene depletion suggests PAK4 as dispensable for mouse pancreas development
Authors: Zhao Miao , Rabieifar Parisa , Costa Tânia D. F. , Zhuang Ting , Minden Audrey , Löhr Matthias , Heuchel Rainer , Strömblad Staffan
Published: July 2017

Constitutive depletion of p21-activated kinase 4 (PAK4) in the mouse causes embryonic lethality associated with heart and brain defects. Given that conventional gene depletion of PAK1 or PAK3 caused functional deficits in the mouse pancreas, while gene depletion of PAK5 or PAK6 did not, we asked if PAK4 might have a functional role in pancreas development. We therefore introduced conditional, Pdx1-Cre-mediated, pancreatic PAK4 gene depletion in the mouse, verified by loss of PAK4 protein expression in the pancreas. PAK4 knock-out (KO) mice were born at Mendelian ratios in both genders. Further, morphological and immunohistochemical examinations and quantifications indicated that exocrine, endocrine and ductal compartments retained the normal proportions and distributions upon PAK4 gene depletion. In addition, body weight records and a glucose tolerance test revealed no differences between WT and PAK4 KO mice. Together, this suggests that PAK4 is dispensable for mouse pancreas development. This will facilitate future use of our Pdx1-Cre-driven conditional PAK4 KO mouse model for testing in vivo potential functions of PAK4 in pancreatic disease models such as for pancreatitis and different pancreatic cancer forms.
Lipid levels and new-onset diabetes in a hypertensive population: the China Stroke Primary Prevention Trial
Authors: Li Leliang , Li Ping , Yang Juan , Huang Xiao , Bao Huihui , Zhang Chunyan , Song Yun , Zhao Min , Ji Meng , Wang Yi , Qian Geng , Tang Genfu , Jiang Shanqun , Dong Qiang , Zhang Yan , Li Jianping , Xu Xiping , Wang Binyan , Huo Yong , Cheng Xiaoshu
Published: July 2017

This study aimed to provide insights into the relationship between lipid levels and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without diabetes (6056 men and 8808 women) aged 45–75 years from the China Stroke Primary Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L at the end of study or self-reported physician diagnosis of diabetes or self-reported use of hypoglycemic agents during follow-up) was analyzed using multivariate analysis. Follow-up was censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD (10.9%, men = 10.8% and women = 10.9%). Increased triglycerides (TG) [odds ratio (OR) = 1.18; 95% confidence interval (CI): 1.13–1.25, P < 0.001], TG/HDL (OR = 1.12; 95%CI: 1.08–1.17, P < 0.001), and decreased high density lipoprotein (HDL) (OR = 0.79; 95%CI: 0.67–0.93, P = 0.005) were associated with NOD, independently from age, gender, body mass index, clinical center, systolic blood pressure, diastolic blood pressure, FPG, smoking, and drinking. Compared to subjects with the methylenetetrahydrofolate reductase (MTHFR) 677 CC and TT genotypes, those with the CT genotype had a higher risk of NOD (OR = 1.54; 95%CI: 1.30–1.81, P for interaction = 0.044) in subjects with high TG. These results suggested that TG and TG/HDL were independent risk factors for NOD in this Chinese hypertensive population. HDL was a protective factor for NOD.
The differentiation of ROR-γt expressing iNKT17 cells is orchestrated by Runx1
Authors: Thapa Puspa , Manso Bryce , Chung Ji Young , Romera Arocha Sinibaldo , Xue Hai-Hui , Angelo Derek B. Sant’ , Shapiro Virginia Smith
Published: July 2017

iNKT cells are a unique lineage of T cells that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized by preferential expression of Tbet, Gata3 and ROR-γt and production of IFN-γ, IL-4 and IL-17, respectively. We demonstrate that the transcriptional regulator Runx1 is essential for the generation of ROR-γt expressing iNKT17 cells. PLZF-cre Runx1 cKO mice lack iNKT17 cells in the thymus, spleen and liver. Runx1-deficient iNKT cells have altered expression of several genes important for iNKT17 differentiation, including decreased expression of IL-7Rα, BATF and c-Maf and increased expression of Bcl11b and Lef1. However, reduction of Lef1 expression or introduction of an IL-7Rα transgene is not sufficient to correct the defect in iNKT17 differentiation, demonstrating that Runx1 is a key regulator of several genes required for iNKT17 differentiation. Loss of Runx1 leads to a severe decrease in iNKT cell numbers in the thymus, spleen and liver. The decrease in cell number is due to a combined decrease in proliferation at Stage 1 during thymic development and increased apoptosis. Thus, we describe a novel role of Runx1 in iNKT cell development and differentiation, particularly in orchestrating iNKT17 differentiation.