bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing Mixing Properties in Model Simulations for CH4 in the Stratosphere
Authors: Wang Zhiting , Hase Nils , Notholt Justus , Dils Bart , Saunois Marielle , Warneke Thorsten , Tian Wenshou 
Published: July 2020

AbstractIsentropic mixing properties in the stratosphere modeled by the forward calculation of an inverse model (TM5‐4DVAR) are evaluated against Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and Microwave Limb Sounder (MLS) observations. The isentropic mixing processes are separated into large‐scale stirring described by the “equivalent length” and small‐scale diffusion described by the diffusivity. Compared to the measurements, we find that the modeled stirring is not strong enough and that the small‐scale diffusivity is too large. TM5‐4DVAR produces excessive mixing‐induced poleward flux for stratospheric CH4. The flux convergence presents negative biases in the tropics and positive biases in the polar regions. The biases cannot be reduced by improving the horizontal resolution only. Modeled isentropic mixing depends on the horizontal as well as the vertical resolution of the model. An increase in vertical resolution reduces numerical diffusion of the model in the vertical. The decreased vertical diffusion leads to reduction in the modeled isentropic diffusivity. Biases in modeled total column‐averaged mixing ratios of CH4 are significant for both models with a coarse vertical resolution of 4° × 6° × 25 (and 2° × 3° × 25, 1° × 1° × 25) and an improved one of 1° × 1° × 40. They are estimated to be 7–14 and 3–7 ppb in the winter extratropics under the assumption that isentropic mixing is dominant over vertical transport on a time scale of 3 days. Correspondingly, resulted biases in inverted CH4 surface emissions are estimated to be 0.5–1 and 0.2–0.5 mg/m2/hr, respectively, in the extratropics.
Methylmercury produced in upper oceans accumulates in deep Mariana Trench fauna
Authors: Sun Ruoyu , Yuan Jingjing , Sonke Jeroen E. , Zhang Yanxu , Zhang Tong , Zheng Wang , Chen Shun , Meng Mei , Chen Jiubin , Liu Yi , Peng Xiaotong , Liu Congqiang 
Published: July 2020

AbstractMonomethylmercury (MMHg) is a potent toxin that bioaccumulates and magnifies in marine food webs. Recent studies show abundant methylated Hg in deep oceans (>1000 m), yet its origin remains uncertain. Here we measured Hg isotope compositions in fauna and surface sediments from the Mariana Trench. The trench fauna at 7000–11000 m depth all have substantially positive mass-independent fractionation of odd Hg isotopes (odd-MIF), which can be generated only in the photic zone via MMHg photo-degradation. Given the identical odd-MIF in trench fauna and North Pacific upper ocean (<1000 m) biota MMHg, we suggest that the accumulated Hg in trench fauna originates exclusively from MMHg produced in upper oceans, which penetrates to depth by sorption to sinking particles. Our findings reveal little in-situ MMHg production in deep oceans and imply that anthropogenic Hg released at the Earth’s surface is much more pervasive across deep oceans than was previously thought.
IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms
Authors: Nadeu Ferran , Mas-de-les-Valls Rut , Navarro Alba , Royo Romina , Martín Silvia , Villamor Neus , Suárez-Cisneros Helena , Mares Rosó , Lu Junyan , Enjuanes Anna , Rivas-Delgado Alfredo , Aymerich Marta , Baumann Tycho , Colomer Dolors , Delgado Julio , Morin Ryan D. , Zenz Thorsten , Puente Xose S. , Campbell Peter J. , Beà Sílvia , Maura Francesco , Campo Elías 
Published: July 2020

AbstractImmunoglobulin (Ig) gene rearrangements and oncogenic translocations are routinely assessed during the characterization of B cell neoplasms and stratification of patients with distinct clinical and biological features, with the assessment done using Sanger sequencing, targeted next-generation sequencing, or fluorescence in situ hybridization (FISH). Currently, a complete Ig characterization cannot be extracted from whole-genome sequencing (WGS) data due to the inherent complexity of the Ig loci. Here, we introduce IgCaller, an algorithm designed to fully characterize Ig gene rearrangements and oncogenic translocations from short-read WGS data. Using a cohort of 404 patients comprising different subtypes of B cell neoplasms, we demonstrate that IgCaller identifies both heavy and light chain rearrangements to provide additional information on their functionality, somatic mutational status, class switch recombination, and oncogenic Ig translocations. Our data thus support IgCaller to be a reliable alternative to Sanger sequencing and FISH for studying the genetic properties of the Ig loci.
The VIP-VPAC2 neuropeptidergic axis is a cellular pacemaking hub of the suprachiasmatic nucleus circadian circuit
Authors: Patton Andrew P. , Edwards Mathew D. , Smyllie Nicola J. , Hamnett Ryan , Chesham Johanna E. , Brancaccio Marco , Maywood Elizabeth S. , Hastings Michael H. 
Published: July 2020

AbstractThe hypothalamic suprachiasmatic nuclei (SCN) are the principal mammalian circadian timekeeper, co-ordinating organism-wide daily and seasonal rhythms. To achieve this, cell-autonomous circadian timing by the ~20,000 SCN cells is welded into a tight circuit-wide ensemble oscillation. This creates essential, network-level emergent properties of precise, high-amplitude oscillation with tightly defined ensemble period and phase. Although synchronised, regional cell groups exhibit differentially phased activity, creating stereotypical spatiotemporal circadian waves of cellular activation across the circuit. The cellular circuit pacemaking components that generate these critical emergent properties are unknown. Using intersectional genetics and real-time imaging, we show that SCN cells expressing vasoactive intestinal polypeptide (VIP) or its cognate receptor, VPAC2, are neurochemically and electrophysiologically distinct, but together they control de novo rhythmicity, setting ensemble period and phase with circuit-level spatiotemporal complexity. The VIP/VPAC2 cellular axis is therefore a neurochemically and topologically specific pacemaker hub that determines the emergent properties of the SCN timekeeper.
Orthophosphate increases the efficiency of slow muscle-myosin isoform in the presence of omecamtiv mecarbil
Authors: Governali Serena , Caremani Marco , Gallart Cristina , Pertici Irene , Stienen Ger , Piazzesi Gabriella , Ottenheijm Coen , Lombardi Vincenzo , Linari Marco 
Published: July 2020

AbstractOmecamtiv mecarbil (OM) is a putative positive inotropic tool for treatment of systolic heart dysfunction, based on the finding that in vivo it increases the ejection fraction and in vitro it prolongs the actin-bond life time of the cardiac and slow-skeletal muscle isoforms of myosin. OM action in situ, however, is still poorly understood as the enhanced Ca2+-sensitivity of the myofilaments is at odds with the reduction of force and rate of force development observed at saturating Ca2+. Here we show, by combining fast sarcomere-level mechanics and ATPase measurements in single slow demembranated fibres from rabbit soleus, that the depressant effect of OM on the force per attached motor is reversed, without effect on the ATPase rate, by physiological concentrations of inorganic phosphate (Pi) (1-10 mM). This mechanism could underpin an energetically efficient reduction of systolic tension cost in OM-treated patients, whenever [Pi] increases with heart-beat frequency.
Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury
Authors: Wilflingseder Julia , Willi Michaela , Lee Hye Kyung , Olauson Hannes , Jankowski Jakub , Ichimura Takaharu , Erben Reinhold , Valerius M. Todd , Hennighausen Lothar , Bonventre Joseph V. 
Published: July 2020

AbstractThe endogenous repair process can result in recovery after acute kidney injury (AKI) with adaptive proliferation of tubular epithelial cells, but repair can also lead to fibrosis and progressive kidney disease. There is currently limited knowledge about transcriptional regulators regulating these repair programs. Herein we establish the enhancer and super-enhancer landscape after AKI by ChIP-seq in uninjured and repairing kidneys on day two after ischemia reperfusion injury (IRI). We identify key transcription factors including HNF4A, GR, STAT3 and STAT5, which show specific binding at enhancer and super-enhancer sites, revealing enhancer dynamics and transcriptional changes during kidney repair. Loss of bromodomain-containing protein 4 function before IRI leads to impaired recovery after AKI and increased mortality. Our comprehensive analysis of epigenetic changes after kidney injury in vivo has the potential to identify targets for therapeutic intervention. Importantly, our data also call attention to potential caveats involved in use of BET inhibitors in patients at risk for AKI.
Photocatalytic hydrogen peroxide splitting on metal-free powders assisted by phosphoric acid as a stabilizer
Authors: Shiraishi Yasuhiro , Ueda Yuki , Soramoto Airu , Hinokuma Satoshi , Hirai Takayuki 
Published: July 2020

AbstractHydrogen peroxide (H2O2) has received increasing attention as an energy carrier. To achieve a sustainable energy society, photocatalytic H2O2 splitting (H2O2 (l) → H2 (g) + O2 (g); ΔG° = + 131 kJ mol−1) is a desirable reaction for on-site H2 generation. However, this reaction has not been reported because conventional photocatalysis decomposes H2O2 by disproportionation (H2O2 (l) → H2O (l) + 1/2O2 (g); ΔG° = −117 kJ mol−1) and by promoting H2O2 reduction instead of H+ reduction. Here we report the successful example of H2O2 splitting. Visible light irradiation of a graphitic carbon nitride loaded with graphene quantum dots as co-catalysts (GQDs/g-C3N4) in a H2O2 solution containing phosphoric acid (H3PO4) produces H2. H3PO4 associates with H2O2 via hydrogen bonding, and this stabilization of H2O2 suppresses its reduction, thus promoting H+ reduction. The all-organic photosystem with H3PO4 as a stabilizer may provide a basis of photocatalytic H2O2 splitting.
Morphological remodeling during recovery of the neuromuscular junction from terminal Schwann cell ablation in adult mice
Authors: Hastings Robert Louis , Mikesh Michelle , Lee Young il , Thompson Wesley J. 
Published: July 2020

AbstractSchwann cells (SCs) are integral to the formation and function of the peripheral nervous system (PNS). Exemplifying their importance, the loss or dysfunction of SCs is a feature of a myriad of diseases and conditions that compromise the PNS. Thus, it remains essential to understand the rules that govern the proliferation, differentiation and reconnection of Schwann cells with peripheral axons. Here, we examined the consequences of locally and acutely ablating terminal Schwann cells (tSCs) at the adult mouse neuromuscular junction (NMJ) by using mice expressing diphtheria toxin receptor (DTR) preferentially in tSCs compared to myelinating SCs followed by local application of diphtheria toxin (DTX). After DTX application, tSCs died but, importantly and contrary to expectations, their associated motor axons did not fully degenerate. Within 3 weeks, tSCs returned and reestablished coverage of the synapse with increased numbers. Furthermore, the post-synaptic muscle fibers displayed increased distinct clusters of acetylcholine receptors and axon terminals exhibited numerous terminal varicosities. The lack of degeneration of bare motor axon terminals and the morphological remodeling that occurs upon the return of tSCs to the NMJ may have wider implications for the mechanisms governing tSC occupancy of the adult NMJ and for conditions that adversely affect tSCs.
Network of clinically-relevant lncRNAs-mRNAs associated with prognosis of hepatocellular carcinoma patients
Authors: Lim Lee Jin , Jin Yu , Yang Henry , Chung Alexander Y. F. , Goh Brian K. P. , Chow Pierce K. H. , Chan Chung Yip , Blanks William K. , Cheow Peng Chung , Lee Ser Yee , Lim Tony K. H. , Chong Samuel S. , Ooi London L. P. J. , Lee Caroline G. 
Published: July 2020

AbstractLong non-coding RNAs (lncRNAs) are often aberrantly expressed in Hepatocellular Carcinoma (HCC). We hypothesize that lncRNAs modulate HCC prognoses through differential deregulation of key lncRNAs affecting important gene network in key cancer pathways associated with pertinent clinical phenotype. Here, we present a novel approach integrating lncRNA-mRNA expression profiles with clinical characteristics to identify lncRNA signatures in clinically-relevant co-expression lncRNA-mRNA networks residing in pertinent cancer pathways. Notably one network, associated with poorer prognosis, comprises five up-regulated lncRNAs significantly correlated (|Pearson Correlation Coefficient|≥ 0.9) with 91 up-regulated genes in the cell-cycle and Rho-GTPase pathways. All 5 lncRNAs and 85/91 (93.4%) of the correlated genes were significantly associated with higher tumor-grade while 3/5 lncRNAs were also associated with no tumor capsule. Interestingly, 2/5 lncRNAs that are correlated with numerous genes in this oncogenic network were experimentally shown to up-regulate genes involved in cell-cycle and transcriptional regulation. Another network comprising 4 down-regulated lncRNAs and 8 down-regulated metallothionein-family genes are significantly associated with tumor invasion. The identification of these key lncRNAs signatures that deregulate important network of genes in key cancer pathways associated with pertinent clinical phenotype may facilitate the design of novel therapeutic strategies targeting these ‘master’ regulators for better patient outcome.
Characterization of DvSSJ1 transcripts targeting the smooth septate junction (SSJ) of western corn rootworm (Diabrotica virgifera virgifera)
Authors: Hu Xu , Boeckman Chad J. , Cong Bin , Steimel Joe P. , Richtman Nina M. , Sturtz Kristine , Wang Yiwei , Walker Carl A. , Yin Jiaming , Unger Anita , Farris Caitlin , Lu Albert L. 
Published: July 2020

AbstractTransgenic maize plants expressing dsRNA targeting western corn rootworm (WCR, Diabrotica virgifera virgifera) DvSSJ1 mRNA, a Drosophila snakeskin (ssk) ortholog, show insecticidal activity and significant plant protection from WCR damage. The gene encodes a membrane protein associated with the smooth sepate junction (SSJ) which is required for intestinal barrier function. To understand the active RNA form that leads to the mortality of WCR larvae by DvSSJ1 RNA interference (RNAi), we characterized transgenic plants expressing DvSSJ1 RNA transcripts targeting WCR DvSSJ1 mRNA. The expression of the silencing cassette results in the full-length transcript of 901 nucleotides containing a 210 bp inverted fragment of the DvSSJ1 gene, the formation of a double-stranded RNA (dsRNA) transcript and siRNAs in transgenic plants. Our artificial diet-feeding study indicates that dsRNAs greater than or equal to approximately 60 base-pairs (bp) are required for DvSSJ1 insecticidal activity. Impact of specificity of dsRNA targeting DvSSJ1 mRNA on insecticidal activities was also evaluated in diet bioassay, which showed a single nucleotide mutation can have a significant impact or abolish diet activities against WCR. These results provide insights as to the functional forms of plant-delivered dsRNA for the protection of transgenic maize from WCR feeding damage and information contributing to the risk assessment of transgenic maize expressing insecticidal dsRNA.
High-resolution characterisation of ESBL/pAmpC-producing Escherichia coli isolated from the broiler production pyramid
Authors: Apostolakos Ilias , Feudi Claudia , Eichhorn Inga , Palmieri Nicola , Fasolato Luca , Schwarz Stefan , Piccirillo Alessandra 
Published: July 2020

AbstractThe presence of extended-spectrum β-lactamase (ESBL) or plasmid-mediated AmpC β-lactamase (pAmpC)-producing Escherichia coli (ESBL/pAmpC-EC) in livestock is a public health risk given the likelihood of their transmission to humans via the food chain. We conducted whole genome sequencing on 100 ESBL/pAmpC-EC isolated from the broiler production to explore their resistance and virulence gene repertoire, characterise their plasmids and identify transmission events derived from their phylogeny. Sequenced isolates carried resistance genes to four antimicrobial classes in addition to cephalosporins. Virulence gene analysis assigned the majority of ESBL/pAmpC-EC to defined pathotypes. In the complex genetic background of ESBL/pAmpC-EC, clusters of closely related isolates from various production stages were identified and indicated clonal transmission. Phylogenetic comparison with publicly available genomes suggested that previously uncommon ESBL/pAmpC-EC lineages could emerge in poultry, while others might contribute to the maintenance and dissemination of ESBL/pAmpC genes in broilers. The majority of isolates from diverse E. coli lineages shared four dominant plasmids (IncK2, IncI1, IncX3 and IncFIB/FII) with identical ESBL/pAmpC gene insertion sites. These plasmids have been previously reported in diverse hosts, including humans. Our findings underline the importance of specific plasmid groups in the dissemination of cephalosporin resistance genes within the broiler industry and across different reservoirs.
Determination of behavior of catalpol hexapropionate in simulated gastric conditions by UPLC–ESI–HRMS
Authors: Cheng Xiaodong , Zhang Qiuxia , Li Zhenxing , Dong Chunhong , Jiang Shiqing , Sun Yu-an , Wang Guoqing 
Published: July 2020

AbstractCatalpol hexapropionate (CP-6) was designed and synthesized as anti-aging drug. In order to investigate the behavior of CP-6 in simulated gastric juice, ultra-high performance liquid chromatography–electrospray ionization–high resolution mass spectrometry was used to determinate the components produced in simulated gastric conditions. Six metabolites were identified with the possible metabolic processes proposed. Hydrolysis may be the main metabolic pathways. The relative contents of CP-6 and its metabolites were determined using their extractive ion chromatograms. The results show that the relative content of CP-6 is rapidly decreased about 15% during the first 0.5 h and generally stable after 0.5 h. The mainly produced metabolites are catalpol penta-propionate (CP-5), catalpol and a spot of catalpol tetra-propionate (CP-4), catalpol tri-propionate (CP-3), catalpol dipropionate (CP-2) and catalpol propionate (CP-1). The metabolitic process of CP-6 may be an hydrolysis under acid conditions. The research results can provide useful information for development and utilization of CP-6 as a pharmaceutical preparation.
Mechanism of Astragalus membranaceus in the treatment of laryngeal cancer based on gene co-expression network and molecular docking
Authors: Dong Kai Feng , Huo Meng Qi , Sun Heng Ya , Li Tian Ke , Li Dan 
Published: July 2020

AbstractAstragalus membranaceus(HUANG QI, HQ) is a kind of traditional Chinese medicine. Researchers have widely concerned its antitumor effect. At present, there is still a lack of research on the treatment of laryngeal cancer with HQ. In this study, we integrated data from the weighted gene co-expression network of laryngeal cancer samples and the components and targets of HQ. A new method for dividing PPI network modules is proposed. Important targets of HQ treatment for laryngeal cancer were obtained through the screening of critical modules. These nodes performed differential expression analysis and survival analysis through external data sets. GSEA enrichment analysis reveals pathways for important targets participation. Finally, molecular docking screened active ingredients in HQ that could interact with important targets. Combined with the laryngeal cancer gene co expression network and HQ PPI network, we obtained the critical module related to laryngeal cancer. Among them, MMP1, MMP3, and MMP10 were chosen as important targets. External data sets demonstrate that their expression in tumor samples is significantly higher than in normal samples. The survival time of patients with high expression group was significantly shortened, which is a negative factor for prognosis. GSEA enrichment analysis found that they are mainly involved in tumor-related pathways such as ECM receptor interaction and Small cell lung cancer. The docking results show that the components that can well bind to important targets of HQ are quercetin, rutin, and Chlorogenic acid, which may be the primary mechanism of the anti-cancer effect of HQ. These findings provide a preliminary research basis for Chinese medicine treatment of laryngeal cancer and offer ideas to related drug design.
High lncSNHG15 expression may predict poor cancer prognosis: a meta-analysis based on the PRISMA and the bio-informatics analysis
Authors: Fang Shi Xu , Chen Cheng , Guo Qiang , Ke Xi Xian , Lu Hong Ling , Xu Gang 
Published: July 2020

Abstract
Background: SNHG15 has been reported to be aberrantly expressed in various tumor tissues and could serve as a promising prognostic cancer biomarker. Previous studies on SNHG15 yielded inconsistent results with insufficient sampling. Here, a meta-analysis was conducted to investigate the prognostic value of SNHG15 in multiple cancers. Methods: Relevant studies were retrieved from six electronic databases including PubMed, Cochrane Library, Google Scholar, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Fifteen publications comprising 1318 patients were included. The publication bias was identified by the Begg’s Test, and the sensitivity analysis was also performed. Results: The results demonstrated a positive correlation between high expression level of lncSNHG15 and short overall survival (hazard ratio (HR) = 2.07, 95% confidence interval (CI), 1.48–2.88; P&lt;0.0001) and disease-free survival (DFS) (HR = 2.32, 95% CI, 1.53–3.53; P&lt;0.0001). The analysis based on different cancer types showed that SNHG15 had the most prominent prognostic potential in Glioma (HR = 3.81; 95% CI, 0.84–42.69; P=0.28). Moreover, the high expression level of lncSNHG15 indicated advanced TNM stage (OR = 2.52; 95% CI, 1.33–4.76; P=0.00001), lymph node metastasis (OR = 2.41, 95% CI, 0.99–4.81; P=0.05), bigger tumor size (OR = 2.06; 95% CI, 1.03–4.13; P=0.04) and poor histological grade (OR = 2.62, 95% CI, 1.90–3.59; P&lt;0.00001), yet no association with distant metastasis (OR = 1.64, 95% CI, 0.40–6.74; P=0.49), age (OR = 0.98, 95% CI, 0.78–1.22; P=0.84) and gender (OR = 0.9, 95% CI, 0.71–1.14; P=0.3838) was found. Its conclusions further confirmed by exploring TCGA databases. Conclusion: It revealed that lncSNHG15 might be a promising prognostic biomarker of multiple cancer types, especially in Glioma.