bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide
Authors: Coon Hilary , Darlington Todd M. , DiBlasi Emily , Callor W. Brandon , Ferris Elliott , Fraser Alison , Yu Zhe , William Nancy , Das Sujan C. , Crowell Sheila E. , Chen Danli , Anderson John S. , Klein Michael , Jerominski Leslie , Cannon Dale , Shabalin Andrey , Docherty Anna , Williams Megan , Smith Ken R. , Keeshin Brooks , Bakian Amanda V. , Christensen Erik , Li Qingqin S. , Camp Nicola J. , Gray Douglas 
Published: October 2018

AbstractSuicide is the 10th leading cause of death in the United States. Although environment has undeniable impact, evidence suggests that genetic factors play a significant role in completed suicide. We linked a resource of ~ 4500 DNA samples from completed suicides obtained from the Utah Medical Examiner to genealogical records and medical records data available on over eight million individuals. This linking has resulted in the identification of high-risk extended families (7–9 generations) with significant familial risk of completed suicide. Familial aggregation across distant relatives minimizes effects of shared environment, provides more genetically homogeneous risk groups, and magnifies genetic risks through familial repetition. We analyzed Illumina PsychArray genotypes from suicide cases in 43 high-risk families, identifying 30 distinct shared genomic segments with genome-wide evidence (p = 2.02E-07–1.30E-18) of segregation with completed suicide. The 207 genes implicated by the shared regions provide a focused set of genes for further study; 18 have been previously associated with suicide risk. Although PsychArray variants do not represent exhaustive variation within the 207 genes, we investigated these for specific segregation within the high-risk families, and for association of variants with predicted functional impact in ~ 1300 additional Utah suicides unrelated to the discovery families. None of the limited PsychArray variants explained the high-risk family segregation; sequencing of these regions will be needed to discover segregating risk variants, which may be rarer or regulatory. However, additional association tests yielded four significant PsychArray variants (SP110, rs181058279; AGBL2, rs76215382; SUCLA2, rs121908538; APH1B, rs745918508), raising the likelihood that these genes confer risk of completed suicide.
Developmental protein kinase C hyper-activation results in microcephaly and behavioral abnormalities in zebrafish
Authors: Liu Taian , Shi Yujian , Chan Matthew T. V. , Peng Gang , Zhang Quan , Sun Xiao , Zhu Zeyao , Xie Yuxin , Sham Kathy W. Y. , Li Jianzhen , Liu Xiaodong , Ho Idy H. T. , Gin Tony , Lu Zhonghua , Wu William K. K. , Cheng Christopher H. K. 
Published: October 2018

AbstractSusceptible genetic polymorphisms and altered expression levels of protein kinase C (PKC)-encoding genes suggest overactivation of PKC in autism spectrum disorder (ASD) development. To delineate the pathological role of PKC, we pharmacologically stimulated its activity during the early development of zebrafish. Results demonstrated that PKC hyper-activation perturbs zebrafish development and induces a long-lasting head size deficit. The anatomical and cellular analysis revealed reduced neural precursor proliferation and newborn neuron formation. β-Catenin that is essential for brain growth is dramatically degraded. Stabilization of β-catenin by gsk3β inhibition partially restores the head size deficit. In addition, the neuropathogenic effect of developmental PKC hyper-activation was further supported by the alterations in the behavioral domain including motor abnormalities, heightened stress reactivity and impaired habituation learning. Taken together, by causally connecting early-life PKC hyper-activation to these neuropathological traits and the impaired neurogenesis, these results suggest that PKC could be a critical pathway in ASD pathogenesis.
Progressive waves of IL-1β release by primary human monocytes via sequential activation of vesicular and gasdermin D-mediated secretory pathways
Authors: Semino Claudia , Carta Sonia , Gattorno Marco , Sitia Roberto , Rubartelli Anna 
Published: October 2018

AbstractIL-1β is an essential cytokine, but its release needs to be strictly controlled to avoid severe inflammatory manifestations. Lacking a signal sequence, IL-1β does not follow the endoplasmic reticulum-Golgi route. Several pathways have been proposed to mediate its release. One involves the translocation of pro-IL-1β into intracellular vesicles of lysosomal origin that eventually fuse with the plasma membrane. Another exploits pores formed on the plasma membrane upon proteolytic cleavage of gasdermin D (GSDMD). Here we investigated how primary monocytes—the main source of IL-1β in humans—control IL-1β release in response to pro-inflammatory stimuli of increasing intensity and found that two different routes are induced depending on the strength of activation. Triggering of Toll-like receptor 4 (TLR4) by LPS induces slow IL-1β release through LAMP2A+ vesicles. In contrast, the simultaneous stimulation of TLR2, TLR4 and TLR7/8 drives high levels of ROS, GSDMD cleavage and faster IL-1β secretion. Drugs blocking ROS production prevent GSDMD cleavage supporting a role of oxidative stress in GSDMD-mediated secretion. Singly stimulated monocytes undergo apoptosis, whereas triple stimulation triggers pyroptosis, which might amplify inflammation. In both cases, however, IL-1β secretion precedes cell death. Inhibition of caspases 4/5 prevents GSDMD cleavage and pore-mediated secretion, but not vesicular release. The two pathways also display other distinct pharmacologic sensitivities that reflect the underlying mechanisms. Remarkably, single TLR4 stimulation is sufficient to activate massive, GSDMD-mediated IL-1β secretion in monocytes from patients affected by Cryopyrin Associated Periodic Syndrome (CAPS), an autoinflammatory disease linked to NLRP3 mutations. The exaggerated sensitivity to activation correlates with high basal ROS levels in CAPS monocytes. In conclusion, the vesicular pathway limits IL-1β release upon low pathogen load while stronger stimulation or concomitant cell stress induce instead uncontrolled secretion via GSDMD leading to detrimental inflammatory manifestations.
A reduced M1-like/M2-like ratio of macrophages in healthy adipose tissue expansion during SGLT2 inhibition
Authors: Miyachi Yasutaka , Tsuchiya Kyoichiro , Shiba Kumiko , Mori Kentaro , Komiya Chikara , Ogasawara Naomi , Ogawa Yoshihiro 
Published: October 2018

AbstractThe adipose tissue includes various stromal cells, such as preadipocytes, endothelial cells, fibroblasts, and immune cells, which are involved in adipose tissue functions. We previously reported that, in obese mice, the sodium–glucose cotransporter 2 inhibitor ipragliflozin (Ipra) promoted the expansion of the epididymal adipose tissue (Epi) with increase of serum ketone body concentration. The Ipra-induced adipose tissue expansion did not deteriorate adipose inflammation, or systemic glucose/lipid metabolism, referred to as “healthy adipose tissue expansion.” Here we found that Ipra promoted healthy adipose tissue expansion with a reduced ratio of pro-inflammatory M1-like adipose tissue macrophages (ATMs) to anti-inflammatory M2-like ATMs. Ipra downregulated the gene expression of interleukin (IL)−15 (Il15) in stromal cells of Epi. IL-15 inhibited lipogenesis in 3T3-L1 cells associated with downregulation of the lipogenic gene. Ketone body β-hydroxybutyrate suppressed Il15 gene induction in M1-polarized cultured macrophages, and a ketogenic diet reproduced the adipose tissue expansion without deteriorating systemic glucose metabolism in mice. Our data indicate that the phenotypic switch of ATMs could mediate healthy adipose tissue expansion by treatment with Ipra, and it may offer new insights into the pathophysiological mechanisms of adipose tissue expansion.
Noninvasive paternal exclusion testing for cystic fibrosis in the first five to eight weeks of gestation
Authors: Zeevi David A. , Zahdeh Fouad , Kling Yehuda , Rosen Tzvia , Renbaum Paul , Ron-El Raphael , Eldar-Geva Talia , Holzer Hananel E. G. , Levy-Lahad Ephrat , Altarescu Gheona 
Published: October 2018

AbstractPrenatal genetic testing is not generally applicable to the very early stages of pregnancy (prior to week 8 gestation), a time period that is crucial to pregnant couples with high risk for transmission of genetic disease to their fetus. Therefore, we developed a new ultra-sensitive targeted next generation sequencing method for noninvasive haplotype-based paternal allele exclusion testing of the cystic fibrosis-associated gene, CFTR. This new method was compared to a conventional library prep and sequencing analysis method and all test results were validated by amniotic fluid testing at later stages of pregnancy. Out of 7 enrolled couples, who provided at least two blood samples (at least one week apart) for noninvasive CFTR testing, a result was obtained for 6 fetuses. Using the new hypersensitive method, all six couples (100%) received a correct diagnosis for the paternal allele as opposed to 3/6 (50%) when tested with the conventional strategy. Among 4 couples who provided just one early pregnancy blood draw for analysis, diagnosis was possible in one fetus, but only using the ultra-sensitive method. Thus, we describe a novel noninvasive CFTR screening method which demonstrates unprecedented fetal allele typing accuracy in the earliest stages of pregnancy.
Functional polarization of human hepatoma HepaRG cells in response to forskolin
Authors: Mayati Abdullah , Moreau Amélie , Le Vée Marc , Bruyère Arnaud , Jouan Elodie , Denizot Claire , Parmentier Yannick , Fardel Olivier 
Published: October 2018

AbstractHepaRG is an original human hepatoma cell line, acquiring highly differentiated hepatic features when exposed to dimethylsulfoxide (DMSO). To search alternatives to DMSO, which may exert some toxicity, we have analyzed the effects of forskolin (FSK), a cAMP-generating agent known to favor differentiation of various cell types. FSK used at 50 µM for 3 days was found to promote polarization of high density-plated HepaRG cells, i.e., it markedly enhanced the formation of functional biliary canaliculi structures. It also increased expressions of various hepatic markers, including those of cytochrome P-450 (CYP) 3A4, of drug transporters like NTCP, OATP2B1 and BSEP, and of metabolism enzymes like glucose 6-phosphatase. In addition, FSK-treated HepaRG cells displayed enhanced activities of CYP3A4, NTCP and OATPs when compared to untreated cells. These polarizing/differentiating effects of FSK were next shown to reflect not only the generation of cAMP, but also the activation of the xenobiotic sensing receptors PXR and FXR by FSK. Co-treatment of HepaRG cells by the cAMP analog Sp-5,6-DCl-cBIMPS and the reference PXR agonist rifampicin reproduced the polarizing effects of FSK. Therefore, FSK may be considered as a relevant alternative to DMSO for getting polarized and differentiated HepaRG cells, notably for pharmacological and toxicological studies.
i-BLESS is an ultra-sensitive method for detection of DNA double-strand breaks
Authors: Biernacka Anna , Zhu Yingjie , Skrzypczak Magdalena , Forey Romain , Pardo Benjamin , Grzelak Marta , Nde Jules , Mitra Abhishek , Kudlicki Andrzej , Crosetto Nicola , Pasero Philippe , Rowicka Maga , Ginalski Krzysztof 
Published: October 2018

AbstractMaintenance of genome stability is a key issue for cell fate that could be compromised by chromosome deletions and translocations caused by DNA double-strand breaks (DSBs). Thus development of precise and sensitive tools for DSBs labeling is of great importance for understanding mechanisms of DSB formation, their sensing and repair. Until now there has been no high resolution and specific DSB detection technique that would be applicable to any cells regardless of their size. Here, we present i-BLESS, a universal method for direct genome-wide DNA double-strand break labeling in cells immobilized in agarose beads. i-BLESS has three key advantages: it is the only unbiased method applicable to yeast, achieves a sensitivity of one break at a given position in 100,000 cells, and eliminates background noise while still allowing for fixation of samples. The method allows detection of ultra-rare breaks such as those forming spontaneously at G-quadruplexes.
The Dat Project, an open and decentralized research data tool
Authors: Robinson Danielle C. , Hand Joe A. , Madsen Mathias Buus , McKelvey Karissa R. 
Published: October 2018

AbstractToday’s scientific data are primarily stored and accessed via centralized Web-based infrastructure. Centralization has advantages but also carries risks such as link rot and content drift, which can hinder scientific progress. It is time to ask whether traditional, centralized Web architecture aligns with scholarly priorities and values, and to collaboratively move towards new approaches that do.
First draft genome sequence of the rock bream in the family Oplegnathidae
Authors: Shin Younhee , Jung Myunghee , Shin Ga-hee , Jung Ho-jin , Baek Su-Jin , Lee Gi-Yong , Kang Byeong-Chul , Shim Jaeyoung , Hong Ji-man , Park Jung Youn , An Cheul Min , Kim Young-Ok , Noh Jae Koo , Kim Ju-Won , Nam Bo-Hye , Park Chan-Il 
Published: October 2018

AbstractThe rock bream (Oplegnathus fasciatus) is one of the most economically valuable marine fish in East Asia, and due to various environmental factors, there is substantial revenue loss in the production sector. Therefore, knowledge of its genome is required to uncover the genetic factors and the solutions to these problems. In this study, we constructed the first draft genome of O. fasciatus as a reference for the family Oplegnathidae. The genome size is estimated to be 749 Mb, and it was assembled into 766 Mb by combining Illumina and PacBio sequences. A total of 24,053 transcripts (23,338 genes) are predicted, and among those transcripts, 23,362 (97%), are annotated with functional terms. Finally, the completeness of the genome assembly was assessed by CEGMA, which resulted in the complete mapping of 220 (88.7%) core genes in the genome. To the best of our knowledge, this is the first draft genome for the family Oplegnathidae.
Modelling and simulation of AC–DC hybrid distribution network based on flexible DC interconnection
Authors: Chen Liang , Jia Mengmeng , Huang Qiang , Yuan Xiaodong 
Published: October 2018

AC and DC hybrid distribution network detailed modelling and multi‐operation conditions of the simulation analysis will effectively support the distribution network project reliable and stable operation. However, at present, large‐scale system‐level simulation of AC–DC hybrid distribution network based on flexible DC is the lack of timeliness and practicability. Based on the real‐time digital simulation platform RT‐LAB, ACDC distribution network model is established, which includes ±20 kV flexible DC interconnection system, distributed photovoltaic, wind power, energy storage system, electric vehicle and the corresponding converter control detailed modelling. In view of the limitation of the balance of energy storage system, the flexible DC interconnection is applied to active distribution network, which can provide power supply when the power gap occurs. The conditions of consumptive mode by the energy storage system, power supply through flexible DC interconnection from external power grid were simulated and analysed. The model verifies the validity of the system application in distribution network. This study provides preliminary design reference for active distribution network construction.
Study on frequency domain dielectric spectroscopy of epoxy resin impregnated paper bushings under damp conditions
Authors: Xu Zuoming , Yi Fuquan , Hu Guanpeng , Wang Xin , Yin Pengbo , Hu Wei , Peng Zongren 
Published: October 2018

Epoxy resin impregnated paper (RIP) bushings are widely used as transformer bushings and wall bushings, but this type of bushing is easy to be dampened. In order to study the effect of moisture on the bushings' insulation performance, a test device was established to simulate the moisture absorption process in the air or N2 gas. Based on the frequency‐domain dielectric spectroscopy (FDS) method, FDS curves that indicate the dielectric loss factor (tan δ) and capacitance (C) under different frequencies were tested and analysed. The results demonstrated that the FDS curve moves to the high frequency direction with the increase of the moisture content, and there exist minus tan δ and a negative peak in low‐frequency band. Since the moisture content is much lower than in the air, tan δ and C under power frequency of the bushing almost unchanged in the N2 gas. However, the tan δ under 0.1 Hz increases sharply with the increase of trace moisture, and the higher moisture content, the greater increase rate. A damp diagnosis method for RIP bushings is proposed based on the FDS curves' frequency translation characteristics and tan δ variation law. Also the results can give references for RIP bushings' insulation diagnosis.
Shielding the magnetic field of wireless power transfer system using zero‐permeability metamaterial
Authors: Lu Conghui , Huang Xiutao , Rong Cancan , Hu Zhaoyang , Chen Junfeng , Tao Xiong , Wang Shengming , Wei Bin , Liu Minghai 
Published: October 2018

The wireless power transfer (WPT) has attracted considerable attention due to its convenience and reliability. However, the electromagnetic leakage of WPT can be harmful to humans and environment. In order to meet safety requirements, electromagnetic leakage to the nearby transmission channel should be controlled below a certain level. Beyond ferrite and metallic shields, several researchers have proposed mu‐near‐zero metamaterial (MNZ MM). However, little work researches the application of MNZ MM in four‐coil WPT systems. Here, the authors propose an optimised MNZ MM for shielding leaked electromagnetic field. Next, the authors setup a miniaturised WPT system loaded with MNZ slab at 13.56 MHz. It can serve as a frequency selector that reflected a specified frequency of 13.56 MHz, while allowing all other frequencies to pass undisturbed. As a result, the transmission efficiency is dramatically reduced at a 30 cm distance. The magnetic field magnitude of the receiver has been decreased. Obviously, the proposed MNZ MM has good performance in magnetic field shielding for WPT systems.
Optimisation of a lithium‐ion battery package based on heat flow field analysis
Authors: Yuan Zheng , Zhao Jin , Huang Fuxia 
Published: October 2018

A lithium‐ion battery package model was established. The influence of inlet velocity, inlet angle and battery space on the heat dissipation capacity of the lithium‐ion battery pack was studied by the method of computational fluid dynamics. The single factor analysis and orthogonal test were used to optimise the lithium‐ion battery package. The results showed that the best cooling effect was obtained under the conditions of 15 m/s wind speed, 8° inlet angle and equal battery spacing; the maximum temperature and temperature difference were reduced by 11.81% and 35%, respectively.
Refluxing synthesis of Mn‐doped ZnO nanoparticles and their applications in dielectric ceramics
Authors: Zhao Ye , Tong Fan , Yang Rong , Qu Xiao , Wang Mao‐Hua 
Published: October 2018

Pure and manganese (Mn)‐doped zinc oxide (ZnO) (0, 1, 2 and 4 wt%) nanoparticles are synthesised by refluxing method. The as‐synthesised nanoparticles are characterised by X‐ray powder diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and energy‐dispersive X‐ray spectroscopy (EDS). The results show that pure and Mn‐doped ZnO nanoparticles have a hexagonal wurtzite structure and the (101) diffraction peaks position of Mn‐doped ZnO shift toward the smaller value of diffraction angle compared with pure ZnO powders, confirming that the Mn2+ were well incorporated into ZnO crystal lattice. Moreover, Mn doping also restrained the growth of particles and the size decreased from 14.9244 to 13.1196 nm with the increase in doping concentration from 0 to 4 wt%. The EDS analysis for 2 wt% Mn‐doped ZnO confirms the presence of Mn in ZnO nanocrystal. The dielectric measurements show that Mn‐doped ZnO ceramics exhibit higher dielectric constant, while dielectric constant and dielectric loss increased continuously with the temperature increased. In addition, 2 wt% Mn‐doped ZnO ceramics showed the high dielectric constant (23 × 103) and low dielectric loss (0.95) at 125°C after sintering at 1000°C for 2 h.
Matrix-propagator approach to compute fluid Love numbers and applicability to extrasolar planets
Authors: Padovan S. , Spohn T. , Baumeister P. , Tosi N. , Breuer D. , Csizmadia Sz. , Hellard H. , Sohl F. 
Published: October 2018

Context.The mass and radius of a planet directly provide its bulk density, which can be interpreted in terms of its overall composition. Any measure of the radial mass distribution provides a first step in constraining the interior structure. The fluid Love numberk2provides such a measure, and estimates ofk2for extrasolar planets are expected to be available in the coming years thanks to improved observational facilities and the ever-extending temporal baseline of extrasolar planet observations.Aims.We derive a method for calculating the Love numbersknof any object given its density profile, which is routinely calculated from interior structure codes.Methods.We used the matrix-propagator technique, a method frequently used in the geophysical community.Results.We detail the calculation and apply it to the case of GJ 436b, a classical example of the degeneracy of mass-radius relationships, to illustrate how measurements ofk2can improve our understanding of the interior structure of extrasolar planets. We implemented the method in a code that is fast, freely available, and easy to combine with preexisting interior structure codes. While the linear approach presented here for the calculation of the Love numbers cannot treat the presence of nonlinear effects that may arise under certain dynamical conditions, it is applicable to close-in gaseous extrasolar planets like hot Jupiters, likely the first targets for whichk2will be measured.
Essential Oils as Treatment Strategy for Alzheimerʼs Disease: Current and Future Perspectives
Authors: Benny Anju , Thomas Jaya 
Published: October 2018

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.