bluuebunny/crossref_metadata_2025 huggingface dataset:
Gambogenic acid inhibits fibroblast growth factor receptor signaling pathway in erlotinib-resistant non-small-cell lung cancer and suppresses patient-derived xenograft growth
Authors: Xu Linfeng , Meng Xiaoxiao , Xu Naihan , Fu Wenwei , Tan Hongsheng , Zhang Li , Zhou Qianjun , Qian Jianan , Tu Shiwei , Li Xueting , Lao Yuanzhi , Xu Hongxi
Published: February 2018

Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition. In this study, we investigated the mechanism of action of GNA in erlotinib-resistant NSCLC and patient-derived cells. The inhibition of GNA on FGFR signaling pathway was examined using biochemical kinase assays. NSCLC cell lines (HCC827, HCC827-Erlotinib-resistant, and H1650) and primary cells from patients with NSCLC with clinical resistance to erlotinib were treated with GNA, erlotinib, or their combination. Both kinase assays and cell- based assays showed that GNA inhibits the phosphorylation of multiple kinases in FGFR signaling pathway in NSCLC. The combination of GNA and erlotinib significantly attenuates the tumor growth of HCC827 and erlotinib-resistant HCC827 xenografts with low toxicity. Importantly, GNA significantly suppresses tumor growth in a lung patient-derived xenograft (PDX) model with FGFR fusion and low EGFR expression. Our findings provide preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy when used as a combined administration.
PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d
Authors: Huang Lanlan , Wen Chuangyu , Yang Xiangling , Lou Qiong , Wang Xiaoyan , Che Jia , Chen Junxiong , Yang Zihuan , Wu Xiaojian , Huang Meijin , Lan Ping , Wang Lei , Iwamoto Aikichi , Wang Jianping , Liu Huanliang
Published: February 2018

PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis, but little is known about the role of PEAK1 in colorectal cancer (CRC) progression. We investigated the expression pattern, function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is overexpressed in CRC tissues and that high PEAK1 expression predicts poor survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1 inhibits cell proliferation, migration, and invasion in vitro and inhibits the growth of tumor xenografts in nude mice. Mechanistic studies revealed that PEAK1 is induced by epidermal growth factor receptor (EGFR) signaling and that PEAK1 is required for KRas-induced CRC cell growth and metastasis. Furthermore, we demonstrated that miR-181d directly targets PEAK1. Ectopic expression of miR-181d reduces the expression of PEAK1 and inhibits the growth and metastasis of CRC cells in vitro. Clinically, miR-181d is downregulated in CRC samples, and low miR-181d is correlated with poor patient survival. Our study demonstrates the importance of PEAK1 in CRC progression and suggests a potential mechanism by which increasing PEAK1 expression in CRC might be the result of EGFR/KRas signal activation and consequent miR-181d repression.
Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle-invasive bladder cancer
Authors: Hu Cheng , Liu Ying , Lin Yuan , Liang Jian-Kai , Zhong Wen-Wen , Li Ke , Huang Wen-Tao , Wang De-Juan , Yan Guang-Mei , Zhu Wen-Bo , Qiu Jian-Guang , Gao Xin
Published: February 2018

Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1 (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections of M1 significant inhibit tumor growth and prolong survival period, antitumor effects of M1 are stronger than those of the first-line chemotherapy agent cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals, which are representative of cell apoptosis, and decreased Ki-67 signals, which are representative of cell proliferation. Moreover, tissue microarray (TMA) analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC presented with low ZAP expression, a finding that is prevalent in advanced MIBC. Our results indicate that the oncolytic virus M1 is a novel agent capable of functioning as a precise and effective therapy for MIBC.
The pro-inflammatory phenotype of the human non-classical monocyte subset is attributed to senescence
Authors: Ong Siew-Min , Hadadi Eva , Dang Truong-Minh , Yeap Wei-Hseun , Tan Crystal Tze-Ying , Ng Tze-Pin , Larbi Anis , Wong Siew-Cheng
Published: February 2018

Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14high/CD16−), intermediate (CD14high/CD16+), and non-classical (CD14low/CD16+). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro, yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types. Hence, we assessed the three monocyte subsets for evidence of senescence, including proliferative status, telomere length, cellular ROS levels, and mitochondrial membrane potential. Indeed, the non-classical subset exhibited the clearest hallmarks of senescence, followed by the intermediate and then the classical subset. In addition, the non-classical subset secreted pro-inflammatory cytokines basally in vitro. The highly pro-inflammatory nature of the non-classical monocytes could be a manifestation of the senescence-associated secretory phenotype (SASP), likely induced by a high basal NF-κB activity and IL-1α production. Finally, we observed an accumulation of the non-classical monocytes, in conjunction with higher levels of plasma TNF-α and IL-8, in the elderly. These factors may contribute to inflamm-aging and age-related inflammatory conditions, such as atherosclerosis and osteoarthritis. With our new understanding that the non-classical monocyte subset is a senescent population, we can now re-examine the role of this subset in disease conditions where this subset expands.
Glucocorticoids promote apoptosis of proinflammatory monocytes by inhibiting ERK activity
Authors: Achuthan Adrian , Aslam Ahmad S. M. , Nguyen Quyen , Lam Pui-Yeng , Fleetwood Andrew J. , Frye Ashlee T. , Louis Cynthia , Lee Ming-Chin , Smith Julia E. , Cook Andrew D. , Olshansky Moshe , Turner Stephen J. , Hamilton John A.
Published: February 2018

Glucocorticoids (GCs) are potent anti-inflammatory drugs whose mode of action is complex and still debatable. One likely cellular target of GCs are monocytes/macrophages. The role of GCs in monocyte survival is also debated. Although both granulocyte macrophage-colony stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) are important regulators of macrophage lineage functions including their survival, the former is often associated with proinflammatory functions while the latter is important in lineage homeostasis. We report here that the GC, dexamethasone, induces apoptosis in GM-CSF-treated human monocytes while having no impact on M-CSF-induced monocyte survival. To understand how GCs, GM-CSF, and M-CSF are regulating monocyte survival and other functions during inflammation, we firstly examined the transcriptomic changes elicited by these three agents in human monocytes, either acting alone or in combination. Transcriptomic and Ingenuity pathway analyses found that dexamethasone differentially modulated dendritic cell maturation and TREM1 signaling pathways in GM-CSF-treated and M-CSF-treated monocytes, two pathways known to be regulated by ERK1/2 activity. These analyses led us to provide evidence that the GC inhibits ERK1/2 activity selectively in GM-CSF-treated monocytes to induce apoptosis. It is proposed that this inhibition of ERK1/2 activity leads to inactivation of p90 ribosomal-S6 kinase and Bad dephosphorylation leading in turn to enhanced caspase-3 activity and subsequent apoptosis. Furthermore, pharmacological inhibition of GC receptor activity restored the ERK1/2 signaling and prevented the GC-induced apoptosis in GM-CSF-treated monocytes. Increased tissue macrophage numbers, possibly from enhanced survival due to mediators such as GM-CSF, can correlate with inflammatory disease severity; also reduction in these numbers can correlate with the therapeutic benefit of a number of agents, including GCs. We propose that the ERK1/2 signaling pathway promotes survival of GM-CSF-treated proinflammatory monocytes, which can be selectively targeted by GCs as a novel mechanism to reduce local monocyte/macrophage numbers and hence inflammation.
Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy
Authors: Ravi Rajani , Noonan Kimberly A. , Pham Vui , Bedi Rishi , Zhavoronkov Alex , Ozerov Ivan V. , Makarev Eugene , V. Artemov Artem , Wysocki Piotr T. , Mehra Ranee , Nimmagadda Sridhar , Marchionni Luigi , Sidransky David , Borrello Ivan M. , Izumchenko Evgeny , Bedi Atul
Published: February 2018

A majority of cancers fail to respond to immunotherapy with antibodies targeting immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) or programmed death-1 (PD-1)/PD-1 ligand (PD-L1). Cancers frequently express transforming growth factor-β (TGFβ), which drives immune dysfunction in the tumor microenvironment by inducing regulatory T cells (Tregs) and inhibiting CD8+ and TH1 cells. To address this therapeutic challenge, we invent bifunctional antibody–ligand traps (Y-traps) comprising an antibody targeting CTLA-4 or PD-L1 fused to a TGFβ receptor II ectodomain sequence that simultaneously disables autocrine/paracrine TGFβ in the target cell microenvironment (a-CTLA4-TGFβRIIecd and a-PDL1-TGFβRIIecd). a-CTLA4-TGFβRIIecd is more effective in reducing tumor-infiltrating Tregs and inhibiting tumor progression compared with CTLA-4 antibody (Ipilimumab). Likewise, a-PDL1-TGFβRIIecd exhibits superior antitumor efficacy compared with PD-L1 antibodies (Atezolizumab or Avelumab). Our data demonstrate that Y-traps counteract TGFβ-mediated differentiation of Tregs and immune tolerance, thereby providing a potentially more effective immunotherapeutic strategy against cancers that are resistant to current immune checkpoint inhibitors.
Biological methane production under putative Enceladus-like conditions
Authors: Taubner Ruth-Sophie , Pappenreiter Patricia , Zwicker Jennifer , Smrzka Daniel , Pruckner Christian , Kolar Philipp , Bernacchi Sébastien , Seifert Arne H. , Krajete Alexander , Bach Wolfgang , Peckmann Jörn , Paulik Christian , Firneis Maria G. , Schleper Christa , Rittmann Simon K.-M. R.
Published: February 2018

The detection of silica-rich dust particles, as an indication for ongoing hydrothermal activity, and the presence of water and organic molecules in the plume of Enceladus, have made Saturn’s icy moon a hot spot in the search for potential extraterrestrial life. Methanogenic archaea are among the organisms that could potentially thrive under the predicted conditions on Enceladus, considering that both molecular hydrogen (H2) and methane (CH4) have been detected in the plume. Here we show that a methanogenic archaeon, Methanothermococcus okinawensis, can produce CH4 under physicochemical conditions extrapolated for Enceladus. Up to 72% carbon dioxide to CH4 conversion is reached at 50 bar in the presence of potential inhibitors. Furthermore, kinetic and thermodynamic computations of low-temperature serpentinization indicate that there may be sufficient H2 gas production to serve as a substrate for CH4 production on Enceladus. We conclude that some of the CH4 detected in the plume of Enceladus might, in principle, be produced by methanogens.
Chiral Ag23 nanocluster with open shell electronic structure and helical face-centered cubic framework
Authors: Liu Chao , Li Tao , Abroshan Hadi , Li Zhimin , Zhang Chen , Kim Hyung J. , Li Gao , Jin Rongchao
Published: February 2018

We report the synthesis and crystal structure of a nanocluster composed of 23 silver atoms capped by 8 phosphine and 18 phenylethanethiolate ligands. X-ray crystallographic analysis reveals that the kernel of the Ag nanocluster adopts a helical face-centered cubic structure with C2 symmetry. The thiolate ligands show two binding patterns with the surface Ag atoms: tri- and tetra-podal types. The tetra-coordination mode of thiolate has not been found in previous Ag nanoclusters. No counter ion (e.g., Na+ and NO3−) is found in the single-crystal and the absence of such ions is also confirmed by X-ray photoelectron spectroscopy analysis, indicating electrical neutrality of the nanocluster. Interestingly, the nanocluster has an open shell electronic structure (i.e., 23(Ag 5s1)–18(SR) = 5e), as confirmed by electron paramagnetic resonance spectroscopy. Time-dependent density functional theory calculations are performed to correlate the structure and optical absorption/emission spectra of the Ag nanocluster.
PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
Authors: Ronson George E. , Piberger Ann Liza , Higgs Martin R. , Olsen Anna L. , Stewart Grant S. , McHugh Peter J. , Petermann Eva , Lakin Nicholas D.
Published: February 2018

PARP1 regulates the repair of DNA single-strand breaks generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication-associated DNA damage owing to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and by stabilising replication forks that encounter BER intermediates.
High-efficiency RNA-based reprogramming of human primary fibroblasts
Authors: Kogut Igor , McCarthy Sandra M. , Pavlova Maryna , Astling David P. , Chen Xiaomi , Jakimenko Ana , Jones Kenneth L. , Getahun Andrew , Cambier John C. , Pasmooij Anna M. G. , Jonkman Marcel F. , Roop Dennis R. , Bilousova Ganna
Published: February 2018

Induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine; however, their potential clinical application is hampered by the low efficiency of somatic cell reprogramming. Here, we show that the synergistic activity of synthetic modified mRNAs encoding reprogramming factors and miRNA-367/302s delivered as mature miRNA mimics greatly enhances the reprogramming of human primary fibroblasts into iPSCs. This synergistic activity is dependent upon an optimal RNA transfection regimen and culturing conditions tailored specifically to human primary fibroblasts. As a result, we can now generate up to 4,019 iPSC colonies from only 500 starting human primary neonatal fibroblasts and reprogram up to 90.7% of individually plated cells, producing multiple sister colonies. This methodology consistently generates clinically relevant, integration-free iPSCs from a variety of human patient’s fibroblasts under feeder-free conditions and can be applicable for the clinical translation of iPSCs and studying the biology of reprogramming.
Author Correction: Uplift of the central transantarctic mountains
Authors: Wannamaker Phil , Hill Graham , Stodt John , Maris Virginie , Ogawa Yasuo , Selway Kate , Boren Goran , Bertrand Edward , Uhlmann Daniel , Ayling Bridget , Green A. Marie , Feucht Daniel
Published: February 2018

The original version of this Article incorrectly referenced the Figures in the Supplementary Information. References in the main Article to Supplementary Figure 7 through to Supplementary Figure 20 were previously incorrectly cited as Supplementary Figure 5 through to Supplementary Figure 18, respectively. This has now been corrected in both the PDF and HTML versions of the Article.
Application of kernel principal component analysis and computational machine learning to exploration of metabolites strongly associated with diet
Authors: Shiokawa Yuka , Date Yasuhiro , Kikuchi Jun
Published: February 2018

Computer-based technological innovation provides advancements in sophisticated and diverse analytical instruments, enabling massive amounts of data collection with relative ease. This is accompanied by a fast-growing demand for technological progress in data mining methods for analysis of big data derived from chemical and biological systems. From this perspective, use of a general “linear” multivariate analysis alone limits interpretations due to “non-linear” variations in metabolic data from living organisms. Here we describe a kernel principal component analysis (KPCA)-incorporated analytical approach for extracting useful information from metabolic profiling data. To overcome the limitation of important variable (metabolite) determinations, we incorporated a random forest conditional variable importance measure into our KPCA-based analytical approach to demonstrate the relative importance of metabolites. Using a market basket analysis, hippurate, the most important variable detected in the importance measure, was associated with high levels of some vitamins and minerals present in foods eaten the previous day, suggesting a relationship between increased hippurate and intake of a wide variety of vegetables and fruits. Therefore, the KPCA-incorporated analytical approach described herein enabled us to capture input–output responses, and should be useful not only for metabolic profiling but also for profiling in other areas of biological and environmental systems.
Evaluation of digital real-time PCR assay as a molecular diagnostic tool for single-cell analysis
Authors: Chang Chia-Hao , Mau-Hsu Daxen , Chen Ke-Cheng , Wei Cheng-Wey , Chiu Chiung-Ying , Young Tai-Horng
Published: February 2018

In a single-cell study, isolating and identifying single cells are essential, but these processes often require a large investment of time or money. The aim of this study was to isolate and analyse single cells using a novel platform, the PanelChip™ Analysis System, which includes 2500 microwells chip and a digital real-time polymerase chain reaction (dqPCR) assay, in comparison with a standard PCR (qPCR) assay. Through the serial dilution of a known concentration standard, namely pUC19, the accuracy and sensitivity levels of two methodologies were compared. The two systems were tested on the basis of expression levels of the genetic markers vimentin, E-cadherin, N-cadherin and GAPDH in A549 lung carcinoma cells at two known concentrations. Furthermore, the influence of a known PCR inhibitor commonly found in blood samples, heparin, was evaluated in both methodologies. Finally, mathematical models were proposed and separation method of single cells was verified; moreover, gene expression levels during epithelial–mesenchymal transition in single cells under TGFβ1 treatment were measured. The drawn conclusion is that dqPCR performed using PanelChip™ is superior to the standard qPCR in terms of sensitivity, precision, and heparin tolerance. The dqPCR assay is a potential tool for clinical diagnosis and single-cell applications.
Transcriptomic signature of drought response in pearl millet (Pennisetum glaucum (L.) and development of web-genomic resources
Authors: Jaiswal Sarika , Antala Tushar J. , Mandavia M. K. , Chopra Meenu , Jasrotia Rahul Singh , Tomar Rukam S. , Kheni Jashminkumar , Angadi U. B. , Iquebal M. A. , Golakia B. A. , Rai Anil , Kumar Dinesh
Published: February 2018

Pearl millet, (Pennisetum glaucum L.), an efficient (C4) crop of arid/semi-arid regions is known for hardiness. Crop is valuable for bio-fortification combating malnutrition and diabetes, higher caloric value and wider climatic resilience. Limited studies are done in pot-based experiments for drought response at gene-expression level, but field-based experiment mimicking drought by withdrawal of irrigation is still warranted. We report de novo assembly-based transcriptomic signature of drought response induced by irrigation withdrawal in pearl millet. We found 19983 differentially expressed genes, 7595 transcription factors, gene regulatory network having 45 hub genes controlling drought response. We report 34652 putative markers (4192 simple sequence repeats, 12111 SNPs and 6249 InDels). Study reveals role of purine and tryptophan metabolism in ABA accumulation mediating abiotic response in which MAPK acts as major intracellular signal sensing drought. Results were validated by qPCR of 13 randomly selected genes. We report the first web-based genomic resource (http://webtom.cabgrid.res.in/pmdtdb/) which can be used for candidate genes-based SNP discovery programs and trait-based association studies. Looking at climatic change, nutritional and pharmaceutical importance of this crop, present investigation has immense value in understanding drought response in field condition. This is important in germplasm management and improvement in endeavour of pearl millet productivity.
Removal of artificial sweeteners and their effects on microbial communities in sequencing batch reactors
Authors: Li Shaoli , Geng Jinju , Wu Gang , Gao Xingsheng , Fu Yingying , Ren Hongqiang
Published: February 2018

Concern is growing over contamination of the environment with artificial sweeteners (ASWs) because of their widespread existence in wastewater treatment plants (WWTPs). To evaluate ASWs removal and the effect on activated sludge, acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC) were introduced individually or in mixture to sequencing batch reactors (SBRs) in environmentally relevant concentrations (100 ppb) for 100 days. Comparisons between ACE removal in a full-scale WWTP and in lab-scale SBRs were conducted. Results showed that CYC and SAC were completely removed, whereas SUC was persistent. However, ACE removal in lab-scale SBRs was significantly greater than in the full-scale WWTP. In SBRs, chemical oxygen demand (COD), ammonia nitrogen (NH4+-N) and total nitrogen (TN) removal appeared unchanged after adding ASWs (p > 0.05). Adenosine triphosphate (ATP) concentrations and triphenyl tetrazolium chloride-dehydrogenase activity (TTC-DHA) declined significantly (p < 0.05). The mixed ASWs had more evident effects than the individual ASWs. Microbial community analyses revealed that Proteobacteria decreased obviously, while Bacteroidetes, Chloroflexi and Actinobacteria were enriched with the addition of ASWs. Redundancy Analysis (RDA) indicated ACE had a greater impact on activated sludge than the other ASWs.
Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound
Authors: Corea Joseph , Ye Patrick , Seo Dongjin , Butts-Pauly Kim , Arias Ana Claudia , Lustig Michael
Published: February 2018

In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.
dynGENIE3: dynamical GENIE3 for the inference of gene networks from time series expression data
Authors: Huynh-Thu Vân Anh , Geurts Pierre
Published: February 2018

The elucidation of gene regulatory networks is one of the major challenges of systems biology. Measurements about genes that are exploited by network inference methods are typically available either in the form of steady-state expression vectors or time series expression data. In our previous work, we proposed the GENIE3 method that exploits variable importance scores derived from Random forests to identify the regulators of each target gene. This method provided state-of-the-art performance on several benchmark datasets, but it could however not specifically be applied to time series expression data. We propose here an adaptation of the GENIE3 method, called dynamical GENIE3 (dynGENIE3), for handling both time series and steady-state expression data. The proposed method is evaluated extensively on the artificial DREAM4 benchmarks and on three real time series expression datasets. Although dynGENIE3 does not systematically yield the best performance on each and every network, it is competitive with diverse methods from the literature, while preserving the main advantages of GENIE3 in terms of scalability.
Hypoxia-induced long non-coding RNA Malat1 is dispensable for renal ischemia/reperfusion-injury
Authors: Kölling Malte , Genschel Celina , Kaucsar Tamas , Hübner Anika , Rong Song , Schmitt Roland , Sörensen-Zender Inga , Haddad George , Kistler Andreas , Seeger Harald , Kielstein Jan T. , Fliser Danilo , Haller Hermann , Wüthrich Rudolf , Zörnig Martin , Thum Thomas , Lorenzen Johan
Published: February 2018

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Non-coding RNAs are crucially involved in its pathophysiology. We identified hypoxia-induced long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) to be upregulated in renal I/R injury. We here elucidated the functional role of Malat1 in vitro and its potential contribution to kidney injury in vivo. Malat1 was upregulated in kidney biopsies and plasma of patients with AKI, in murine hypoxic kidney tissue as well as in cultured and ex vivo sorted hypoxic endothelial cells and tubular epithelial cells. Malat1 was transcriptionally activated by hypoxia-inducible factor 1-α. In vitro, Malat1 inhibition reduced proliferation and the number of endothelial cells in the S-phase of the cell cycle. In vivo, Malat1 knockout and wildtype mice showed similar degrees of outer medullary tubular epithelial injury, proliferation, capillary rarefaction, inflammation and fibrosis, survival and kidney function. Small-RNA sequencing and whole genome expression analysis revealed only minor changes between ischemic Malat1 knockout and wildtype mice. Contrary to previous studies, which suggested a prominent role of Malat1 in the induction of disease, we did not confirm an in vivo role of Malat1 concerning renal I/R-injury.
The novel dithiocarbamate, DpdtC suppresses HER2-overexpressed cancer cells by up-regulating NDRG1 via inactivation of HER2-ERK 1/2 signaling
Authors: Yang Yun , Liu Youxun , Guo Rui , Fu Yun , Zhang Ziheng , Zhang Pengfei , Zhou Pingxin , Wang Tingting , Huang Tengfei , Li Xiaotong , Li Changzheng
Published: February 2018

Dithiocarbamate has been tested for its effective anti-tumor activity, but the underlying mechanism remains unclear. We previously prepared a novel diththiocarbamate derivative, DpdtC with an ability of catalase inhibition. Here, we for the first time investigated the growth inhibition effects of DpdtC on HER2-amplified cancer cells and elucidated its mechanism of action. Results showed that DpdtC exerted the potent anti-tumor effects against HER2-overexpressed SK-OV-3 and SK-BR-3 cells, especially on SK-OV-3 cells with a higher NDRG1 level, which was also confirmed in the SK-OV-3 xenograft model. Interestingly, we observed that NDRG1 was up-regulated, while membrane expression of HER2 was regressed in SK-OV-3 cells upon DpdtC treatment. In agreement, silencing endogenous NDRG1 also increased the expression of HER2 in SK-OV-3 cells, while overexpressing NDRG1 decreased HER2 expression in SK-BR-3 cells. Furthermore, our results showed the formation of the EGFR/HER2 heterodimer was attenuated and phosphorylation of ERK1/2 was inhibited in SK-OV-3 cells when treated with DpdtC. Collectively, these observations demonstrated that NDRG1 plays an important role in mediating the inhibition effects of DpdtC in HER2-overexpressed cancer cells via selective targeting of the HER2-ERK1/2 pathway. Hence, our investigation suggests that up-regulation of NDRG1 by DpdtC is a promising therapeutic approach in HER2-overexpressed cancers.
Effect of the environment microbiota on the flavour of light-flavour Baijiu during spontaneous fermentation
Authors: Pang Xiao-Na , Han Bei-Zhong , Huang Xiao-Ning , Zhang Xin , Hou Lin-Feng , Cao Ming , Gao Li-Juan , Hu Guang-Hui , Chen Jing-Yu
Published: February 2018

Light-flavour Baijiu is a type of Chinese liquor with a pure and mild flavour produced by traditional spontaneous solid-state fermentation. The flavour of this liquor has been found to vary in the different periods of annual production. To explore the factors affecting flavour, the microbiota of the surrounding environment, starter and fermentation process in different periods were investigated. Results showed that the ester content and acidity of light-flavour Baijiu were significantly lower when annual production was resumed after a summer break. HCA plot of volatile flavour profile and bacterial PCoA results indicated that the differences occurred at later stages, mainly due to different structures of Lactobacillus. Correlation analysis by O2PLS indicated that Lactobacillus positively correlated with esters. Species-level analysis showed that the lack of L. acetotolerans on the surface of the jar might cause a lag in fermentation and lower ester content. Thereafter, L. acetotolerans was revived during fermentation and enriched on the surface of the jar, which promoted ester formation. As important sources of L. acetotolerans, the air and fermentation jars played a critical role during fermentation. Therefore, this systematic study on environmental microbial ecology is valuable for quality control and to explore environmental microbiota functions during spontaneous fermentation.
Structural transformation of layered double hydroxides: an in situ TEM analysis
Authors: Hobbs Christopher , Jaskaniec Sonia , McCarthy Eoin K. , Downing Clive , Opelt Konrad , Güth Konrad , Shmeliov Aleksey , Mourad Maurice C. D. , Mandel Karl , Nicolosi Valeria
Published: February 2018

A comprehensive nanoscale understanding of layered double hydroxide (LDH) thermal evolution is critical for their current and future applications as catalysts, flame retardants and oxygen evolution performers. In this report, we applied in situ transmission electron microscopy (TEM) to extensively characterise the thermal progressions of nickel-iron containing (Ni-Fe) LDH nanomaterials. The combinative approach of TEM and selected area electron diffraction (SAED) yielded both a morphological and crystallographic understanding of such processes. As the Ni-Fe LDH nanomaterials are heated in situ, an amorphization occurred at 250 °C, followed by a transition to a heterogeneous structure of NiO particles embedded throughout a NiFe2O4 matrix at 850 °C, confirmed by high-resolution TEM and scanning TEM. Further electron microscopy characterisation methodologies of energy-filtered TEM were utilised to directly observe these mechanistic behaviours in real time, showing an evolution and nucleation to an array of spherical NiO nanoparticles on the platelet surfaces. The versatility of this characterisation approach was verified by the analogous behaviours of Ni-Fe LDH materials heated ex situ as well as parallel in situ TEM and SAED comparisons to that of an akin magnesium-aluminium containing (Mg-Al) LDH structure. The in situ TEM work hereby discussed allows for a state-of-the-art understanding of the Ni-Fe material thermal evolution. This is an important first, which reveals pivotal information, especially when considering LDH applications as catalysts and flame retardants.
Study on behaviors and performances of universal N-glycopeptide enrichment methods
Authors: Xue Yu , Xie Juanjuan , Fang Pan , Yao Jun , Yan Guoquan , Shen Huali , Yang Pengyuan
Published: February 2018

Glycosylation is a crucial process in protein biosynthesis.
Formation of a water-mediated assembly of two neutral copper(ii) Schiff base fragments with a Cu2(NCS)4moiety: exploration of non-covalent C–H⋯π(bimetallo ring) interactions
Authors: Roy Sourav , Drew Michael G. B. , Bauzá Antonio , Frontera Antonio , Chattopadhyay Shouvik
Published: February 2018

The energetic features of dimer formation and water encapsulation in an interesting copper(ii) Schiff base complex, [(CuL)2⊂(H2O)][Cu2(μ1,3-NCS)2(NCS)2], have been studied using DFT calculations.
Optical nano-biosensing interface via nucleic acid amplification strategy: construction and application
Authors: Zhou Hong , Liu Jing , Xu Jing-Juan , Zhang Shu-Sheng , Chen Hong-Yuan
Published: February 2018

This article reviews recent smart constructions and applications of optical nano-biosensing interfaces assisted by a nucleic acid amplification strategy.
Switching of inter-valence charge transfer in stimuli-responsive bis(ferrocenyl)porphyrin
Authors: Sundharamurthi Subramani , Sudha Kaliyaperumal , Karthikaikumar Samuvelnesamani , Abinaya Kalyanasundaram , Reddy V. Raghavendra , Kalimuthu Palanisamy
Published: February 2018

Stimuli-responsive 5,15-bis(ferrocenyl)-10,20-bis(mesityl)porphyrin (BFP) was synthesized and used to demonstrate the ON/OFF switching of inter-valence charge transfer (IVCT) between ferrocene terminals.
Grafted monolayers of the neutral Cu(ii) complex of a dioxo-2,3,2 ligand: surfaces with decreased antibacterial action
Authors: Taglietti A. , Grisoli P. , Dacarro G. , Gattesco A. , Mangano C. , Pallavicini P.
Published: February 2018

A monolayer of the neutral Cu2+ complex of a silane-bearing diamino–diamido ligand is formed on glass, exhibiting (decreased) antibacterial properties.
Fluorescent zinc(ii)-based metal–organic frameworks for nitroaromatics sensing
Authors: Ma Yujie , Xu Guanhong , Wei Fangdi , Cen Yao , Song Yueyue , Shi Menglan , Xu Xiaoman , Sohail Muhammad , Hu Qin
Published: February 2018

A new structural metal–organic framework with fluorescence properties was synthesized and applied for sensitive and selective sensing of nitroaromatics.
Impact of cathepsin B-sensitive triggers and hydrophilic linkers onin vitroefficacy of novel site-specific antibody–drug conjugates
Authors: Bryden Francesca , Martin Camille , Letast Stéphanie , Lles Eva , Viéitez-Villemin Inmaculada , Rousseau Anaïs , Colas Cyril , Brachet-Botineau Marie , Allard-Vannier Emilie , Larbouret Christel , Viaud-Massuard Marie-Claude , Joubert Nicolas
Published: February 2018

Promising anti-HER2 site-specific ADCs with anin vitroefficacy equivalent to Kadcyla®.
Alkane guest packing drives switching between multimeric deep-cavity cavitand assembly states
Authors: Barnett J. Wesley , Tang Du , Gibb Bruce C. , Ashbaugh Henry S.
Published: February 2018

Alkane guest transfer into aqueous dimeric, tetrameric, hexameric, and octameric assemblies of the deep-cavity cavitand TEMOA is examined using molecular simulations.
Improved fluorescence imaging and synergistic anticancer phototherapy of hydrosoluble gold nanoclusters assisted by a novel two-level mesoporous canal structured silica nanocarrier
Authors: Yang Ying , Wang Shuxin , Xu Changzhi , Xie Anjian , Shen Yuhua , Zhu Manzhou
Published: February 2018

This work described a novel combination of gold nanoclusters with two-level mesoporous silica nanocarriers for improved fluorescence imaging assisted photodynamic/photothermal therapy of cancer.
Hydrogen-motivated electrolysis of sodium carbonate with extremely low cell voltage
Authors: Liu Jia , Xiong Hailang , Tong Siyuan , Tang Yang , Chen Yongmei , Sun Yanzhi , Yang Xiaojin , Wan Pingyu , Khan Zia Ul Haq
Published: February 2018

Hydrogen-motivated electrolysis of Na2CO3 for energy-saving production of NaOH and CO2/NaHCO3 is realized by using HOR to insert H+ into the anolyte and by using HER to extract H+ out of the catholyte.
Neutral and anionic zinc compounds supported by a bis(imino)phenyl NCN ligand
Authors: Nguyen Minh Tho , Gabidullin Bulat , Nikonov Georgii I.
Published: February 2018

The new zinc complexes 2,6-(ArNCH)2C6H3ZnBu (6) and 2,6-(ArNCH)2C6H3ZnCl2Li(THF)3 (7), supported by a bis(imino)phenyl NCN pincer ligand, were prepared (Ar = 2,6-iPr2C6H3).
The Taiji and Eight Trigrams chemistry philosophy of chiral iridium(iii) complexes with triplex stereogenic centers
Authors: Yan Zhi-Ping , Luo Xu-Feng , Liao Kang , Lin Zi-Xuan , Wu Zheng-Guang , Zhou Yong-Hui , Zheng You-Xuan
Published: February 2018

Eight Ir(iii) isomers with triplex stereogenic centers are corresponding to the old Chinese philosophy Taiji and Eight Trigrams. The ECD and CPL spectra of four pair isomers show perfect mirror-images with a glum factor around 0.003.
Tuning the catalytic activity of colloidal noble metal nanocrystals by using differently charged surfactants
Authors: Hu J. H. , Mi H. , Wang N. , Zhu H. Y. , Guo W. Y. , Zhang S. R. , Shi F. , Lei Z. B. , Liu Z.-H. , Jiang R. B.
Published: February 2018

The catalytic activity of metal nanocrystals is tuned by using differently charged surfactants.
Correction: Surface modification of carbon cloth anodes for microbial fuel cells using atmospheric-pressure plasma jet processed reduced graphene oxides
Authors: Chang Shih-Hang , Huang Bo-Yen , Wan Ting-Hao , Chen Jian-Zhang , Chen Bor-Yann
Published: February 2018

Correction for ‘Surface modification of carbon cloth anodes for microbial fuel cells using atmospheric-pressure plasma jet processed reduced graphene oxides’ by Shih-Hang Chang et al., RSC Adv., 2017, 7, 56433–56439.
Correction: Compositional effect on the fabrication of AgxPd1−x alloy nanoparticles on c-plane sapphire at distinctive stages of the solid-state-dewetting of bimetallic thin films
Authors: Pandey Puran , Kunwar Sundar , Sui Mao , Bastola Sushil , Lee Jihoon
Published: February 2018

Correction for ‘Compositional effect on the fabrication of AgxPd1−x alloy nanoparticles on c-plane sapphire at distinctive stages of the solid-state-dewetting of bimetallic thin films’ by Puran Pandey et al., RSC Adv., 2017, 7, 55471–55481.
Partially‐organic relay design for improved on‐state resistance
Authors: Pan Y. , Jeon J.
Published: February 2018

Previously‐reported purely‐organic microelectromechanical relays suffer from a high on‐state resistance above 1 GΩ, which makes them unsuitable for relay‐based organic integrated circuits. This letter demonstrates partially‐organic relays that employ a metal and/or a metal oxide for their contacts to alleviate the issue.
Urban link travel time estimation using traffic states‐based data fusion
Authors: Zhu Lin , Guo Fangce , Polak John W. , Krishnan Rajesh
Published: February 2018

Estimated travel time is a key input for many intelligent transport systems (ITS) applications and traffic management functions. There are numerous studies that show that fusing data from different sources such as global positioning system (GPS), Bluetooth, mobile phone network (MPN), and inductive loop detector (ILD) can result in more accurate travel time estimation. However, to date, there has been little research investigating the contribution of individual data sources to the quality of the final estimate or how this varies according to source‐specific data quality under different traffic states. Here, three different data sources, namely bus‐based GPS (bGPS) data, ILD data, and MPN data, of varying quality are combined using three different data fusion techniques of varying complexity. In order to quantify the accuracy of travel time estimation, travel time calculated using automatic number plate recognition (ANPR) data are used as the ‘ground truth’. The final results indicate that fusing multiple data together does not necessarily enhance the accuracy of travel time estimation. The results also show that even in dense urban areas, bGPS data, when combined with ILD data, can provide reasonable travel time estimates of general traffic stream under different traffic states.
Large-amplitude late-time radio variability in GRB 151027B
Authors: Greiner J. , Bolmer J. , Wieringa M. , van der Horst A. J. , Petry D. , Schulze S. , Knust F. , de Bruyn G. , Krühler T. , Wiseman P. , Klose S. , Delvaux C. , Graham J. F. , Kann D. A. , Moin A. , Nicuesa-Guelbenzu A. , Schady P. , Schmidl S. , Schweyer T. , Tanga M. , Tingay S. , van Eerten H. , Varela K.
Published: February 2018

Context. Deriving physical parameters from gamma-ray burst (GRB) afterglow observations remains a challenge, even 20 years after the discovery of afterglows. The main reason for the lack of progress is that the peak of the synchrotron emission is in the sub-mm range, thus requiring radio observations in conjunction with X-ray/optical/near-infrared data in order to measure the corresponding spectral slopes and consequently remove the ambiguity with respect to slow vs. fast cooling and the ordering of the characteristic frequencies.

Aims. We have embarked on a multifrequency, multi-epoch observing campaign to obtain sufficient data for a given GRB that allows us to test the simplest version of the fireball afterglow model.

Methods. We observed GRB 151027B, the 1000th Swift-detected GRB, with GROND in the optical–near-IR, ALMA in the sub-millimeter, ATCA in the radio band; we combined this with public Swift/XRT X-ray data.

Results. While some observations at crucial times only return upper limits or surprising features, the fireball model is narrowly constrained by our data set, and allows us to draw a consistent picture with a fully determined parameter set. Surprisingly, we find rapid, large-amplitude flux density variations in the radio band which are extreme not only for GRBs, but generally for any radio source. We interpret them as scintillation effects, though their extreme nature requires the scattering screen to be at a much smaller distance than usually assumed, multiple screens, or a combination of the two.

Conclusions. The data are consistent with the simplest fireball scenario for a blast wave moving into a constant-density medium, and slow-cooling electrons. All fireball parameters are constrained at or better than a factor of 2, except for the density and the fraction of the energy in the magnetic field which has a factor of 10 uncertainty in both directions.
Intriguing X-ray and optical variations of the γ Cassiopeiae analog HD 45314
Authors: Rauw G. , Nazé Y. , Smith M. A. , Miroshnichenko A. S. , Guarro Fló J. , Campos F. , Prendergast P. , Danford S. , González-Pérez J. N. , Hempelmann A. , Mittag M. , Schmitt J. H. M. M. , Schröder K.-P. , Zharikov S. V.
Published: February 2018

Context. A growing number of Be and Oe stars, named the γ Cas stars, are known for their unusually hard and intense X-ray emission. This emission could either trace accretion by a compact companion or magnetic interaction between the star and its decretion disk.

Aims. To test these scenarios, we carried out a detailed optical monitoring of HD 45314, the hottest member of the class of γ Cas stars, along with dedicated X-ray observations on specific dates.

Methods. High-resolution optical spectra were taken to monitor the emission lines formed in the disk, while X-ray spectroscopy was obtained at epochs when the optical spectrum of the Oe star was displaying peculiar properties.

Results. Over the last four years, HD 45314 has entered a phase of spectacular variations. The optical emission lines have undergone important morphology and intensity changes including transitions between single- and multiple-peaked emission lines as well as shell events, and phases of (partial) disk dissipation. Photometric variations are found to be anti-correlated with the equivalent width of the Hα emission. Whilst the star preserved its hard and bright X-ray emission during the shell phase, the X-ray spectrum during the phase of (partial) disk dissipation was significantly softer and weaker.

Conclusions. The observed behaviour of HD 45314 suggests a direct association between the level of X-ray emission and the amount of material simultaneously present in the Oe disk as expected in the magnetic star-disk interaction scenario.
Atmospheric Weathering of Historic Monuments and Their Related Conservation Issues
Authors: Caner-Saltık Emine N.
Published: February 2018

Atmospheric environment affects the materials of historic monuments and their structure starting from the time of their construction. Daily and seasonal changes in temperature and humidity, wind, snow and rainfall, soluble salts carried by water, biological agents, pollutant gases and particulate matter are some of the agents in atmospheric environment that introduce weathering by physical, chemical and biological processes in the materials of the monuments such as natural building stones, bricks, mortars and plasters, mud brick etc. The weathering processes need to be well diagnosed by identification of main mechanisms of decay and major responsible agents, degree and depth of deterioration expressed with measurable parameters of physical, physicomechanical properties, and micro structural changes together with their distribution on the monument. Success of conservation treatments strongly depend on those diagnostic studies and compatibility of the treatments with the deteriorated and relatively sound parts of the historic materials. Current approach to materials conservation is to be able to make minimum intervention to historic material by targeting the conservation treatment to the deteriorated area for the purpose of controlling the deterioration factors and achieving compatible and durable conservation of historical material. In this presentation, two examples of diagnostic research and conservation treatments based on and guided by the diagnostic results are summarized concerning historic stone monuments exposed to atmospheric environment since more than two thousand years. The first example is on the marble walls of Temple of Augustus in Ankara exposed to polluted urban atmosphere. The second example is on the limestone statues of Nemrut Mount Monument in Adıyaman-Turkey, exposed to rural atmosphere with harsh climatic conditions. Finally, a brief discussion on current research issues related to historic materials conservation in atmospheric environment is made.