bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring lithium’s transcriptional mechanisms of action in bipolar disorder: a multi-step study
Authors: Akkouh Ibrahim A. , Skrede Silje , Holmgren Asbjørn , Ersland Kari M. , Hansson Lars , Bahrami Shahram , Andreassen Ole A. , Steen Vidar M. , Djurovic Srdjan , Hughes Timothy
Published: October 2019

Lithium has been the first-line treatment for bipolar disorder (BD) for more than six decades. Although the molecular effects of lithium have been studied extensively and gene expression changes are generally believed to be involved, the specific mechanisms of action that mediate mood regulation are still not known. In this study, a multi-step approach was used to explore the transcriptional changes that may underlie lithium’s therapeutic efficacy. First, we identified genes that are associated both with lithium exposure and with BD, and second, we performed differential expression analysis of these genes in brain tissue samples from BD patients (n = 42) and healthy controls (n = 42). To identify genes that are regulated by lithium exposure, we used high-sensitivity RNA-sequencing of corpus callosum (CC) tissue samples from lithium-treated (n = 8) and non-treated (n = 9) rats. We found that lithium exposure significantly affected 1108 genes (FDR < 0.05), 702 up-regulated and 406 down-regulated. These genes were mostly enriched for molecular functions related to signal transduction, including well-established lithium-related pathways such as mTOR and Wnt signaling. To identify genes with differential expression in BD, we performed expression quantitative trait loci (eQTL) analysis on BD-associated genetic variants from the most recent genome-wide association study (GWAS) using three different gene expression databases. We found 307 unique eQTL genes regulated by BD-associated variants, of which 12 were also significantly modulated by lithium treatment in rats. Two of these showed differential expression in the CC of BD cases: RPS23 was significantly down-regulated (p = 0.0036, fc = 0.80), while GRIN2A showed suggestive evidence of down-regulation in BD (p = 0.056, fc = 0.65). Crucially, GRIN2A was also significantly up-regulated by lithium in the rat brains (p = 2.2e-5, fc = 1.6), which suggests that modulation of GRIN2A expression may be a part of the therapeutic effect of the drug. These results indicate that the recent upsurge in research on this central component of the glutamatergic system, as a target of novel therapeutic agents for affective disorders, is warranted and should be intensified.
Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells
Authors: Kouzi Farah , Zibara Kazem , Bourgeais Jerome , Picou Frederic , Gallay Nathalie , Brossaud Julie , Dakik Hassan , Roux Benjamin , Hamard Sophie , Le Nail Louis-Romee , Hleihel Rita , Foucault Amelie , Ravalet Noemie , Rouleux-Bonnin Florence , Gouilleux Fabrice , Mazurier Frederic , Bene Marie C. , Akl Haidar , Gyan Emmanuel , Domenech Jorge , El-Sabban Marwan , Herault Olivier
Published: October 2019

The bone marrow (BM) niche impacts the progression of acute myeloid leukemia (AML) by favoring the chemoresistance of AML cells. Intimate interactions between leukemic cells and BM mesenchymal stromal cells (BM-MSCs) play key roles in this process. Direct intercellular communications between hematopoietic cells and BM-MSCs involve connexins, components of gap junctions. We postulated that blocking gap junction assembly could modify cell–cell interactions in the leukemic niche and consequently the chemoresistance. The comparison of BM-MSCs from AML patients and healthy donors revealed a specific profile of connexins in BM-MSCs of the leukemic niche and the effects of carbenoxolone (CBX), a gap junction disruptor, were evaluated on AML cells. CBX presents an antileukemic effect without affecting normal BM-CD34+ progenitor cells. The proapoptotic effect of CBX on AML cells is in line with the extinction of energy metabolism. CBX acts synergistically with cytarabine (Ara-C) in vitro and in vivo. Coculture experiments of AML cells with BM-MSCs revealed that CBX neutralizes the protective effect of the niche against the Ara-C-induced apoptosis of leukemic cells. Altogether, these results suggest that CBX could be of therapeutic interest to reduce the chemoresistance favored by the leukemic niche, by targeting gap junctions, without affecting normal hematopoiesis.
Human iPSC-derived iMSCs improve bone regeneration in mini-pigs
Authors: Jungbluth Pascal , Spitzhorn Lucas-Sebastian , Grassmann Jan , Tanner Stephan , Latz David , Rahman Md Shaifur , Bohndorf Martina , Wruck Wasco , Sager Martin , Grotheer Vera , Kröpil Patric , Hakimi Mohssen , Windolf Joachim , Schneppendahl Johannes , Adjaye James
Published: October 2019

Autologous bone marrow concentrate (BMC) and mesenchymal stem cells (MSCs) have beneficial effects on the healing of bone defects. To address the shortcomings associated with the use of primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) have been proposed as an alternative. The aim of this study was to investigate the bone regeneration potential of human iMSCs combined with calcium phosphate granules (CPG) in critical-size defects in the proximal tibias of mini-pigs in the early phase of bone healing compared to that of a previously reported autograft treatment and treatment with a composite made of either a combination of autologous BMC and CPG or CPG alone. iMSCs were derived from iPSCs originating from human fetal foreskin fibroblasts (HFFs). They were able to differentiate into osteoblasts in vitro, express a plethora of bone morphogenic proteins (BMPs) and secrete paracrine signaling-associated cytokines such as PDGF-AA and osteopontin. Radiologically and histomorphometrically, HFF-iMSC + CPG transplantation resulted in significantly better osseous consolidation than the transplantation of CPG alone and produced no significantly different outcomes compared to the transplantation of autologous BMC + CPG after 6 weeks. The results of this translational study imply that iMSCs represent a valuable future treatment option for load-bearing bone defects in humans.
EWS-FLI1-mediated tenascin-C expression promotes tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation in Ewing sarcoma
Authors: He Shaohui , Huang Quan , Hu Jinbo , Li Lei , Xiao Yanbin , Yu Hongyu , Han Zhitao , Wang Ting , Zhou Wang , Wei Haifeng , Xiao Jianru
Published: October 2019

Background

The extracellular matrix has been critically associated with the tumorigenesis and progression of Ewing sarcoma (ES). However, the regulatory and prognostic roles of tenascin-C (TNC) in ES remain unclear.

Methods

TNC expression was examined in specimens by immunohistochemistry, and the association of TNC expression with ES patient survival was also analysed. TNC-knockout cell lines were constructed using CRISPR/Cas9 methods. In vitro experiments and in vivo bioluminescent imaging using BALB/c nude mice were conducted to evaluate the effect of TNC on ES tumour progression. RNA sequencing was performed, and the underlying mechanism of TNC was further explored.

Results

TNC was overexpressed in ES tissue and cell lines, and TNC overexpression was associated with poor survival in ES patients. TNC enhanced cell proliferation, migration and angiogenesis in vitro and promoted ES metastasis in vivo. The oncoprotein EWS-FLI1 profoundly increased TNC expression by directly binding to the TNC promoter region. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) upregulation induced by Yes-associated protein (YAP) activation was responsible for TNC-regulated ES tumour progression. Activated integrin α5β1 signalling might be correlated with YAP dephosphorylation and nuclear translocation.

Conclusions

TNC may promote ES tumour progression by targeting MALAT1 through integrin α5β1-mediated YAP activation.
ROS-mediated inactivation of the PI3K/AKT pathway is involved in the antigastric cancer effects of thioredoxin reductase-1 inhibitor chaetocin
Authors: Wen Chuangyu , Wang Huihui , Wu Xiaobin , He Lu , Zhou Qian , Wang Fang , Chen Siyu , Huang Lanlan , Chen Junxiong , Wang Huashe , Ye Weibiao , Li Wende , Yang Xiangling , Liu Huanliang , Peng Junsheng
Published: October 2019

Novel drugs are urgently needed for gastric cancer (GC) treatment. The thioredoxin-thioredoxin reductase (TRX-TRXR) system has been found to play a critical role in GC tumorigenesis and progression. Thus, agents that target the TRX-TRXR system may be highly efficacious as GC treatments. In this study, we showed that chaetocin, a natural product isolated from the Chaetomium species of fungi, inhibited proliferation, induced G2/M phase arrest and caspase-dependent apoptosis in both in vitro and in vivo models (cell xenografts and patient-derived xenografts) of GC. Chaetocin inactivated TRXR-1, resulting in the accumulation of reactive oxygen species (ROS) in GC cells; overexpression of TRX-1 as well as cotreatment of GC cells with the ROS scavenger N-acetyl-L-cysteine attenuated chaetocin-induced apoptosis; chaetocin-induced apoptosis was significantly increased when GC cells were cotreated with auranofin. Moreover, chaetocin was shown to inactivate the PI3K/AKT pathway by inducing ROS generation; AKT-1 overexpression also attenuated chaetocin-induced apoptosis. Taken together, these results reveal that chaetocin induces the excessive accumulation of ROS via inhibition of TRXR-1. This is followed by PI3K/AKT pathway inactivation, which ultimately inhibits proliferation and induces caspase-dependent apoptosis in GC cells. Chaetocin therefore may be a potential agent for GC treatment.
DDX17 promotes hepatocellular carcinoma progression via inhibiting Klf4 transcriptional activity
Authors: Xue Ying , Jia Xuebing , Li Changcan , Zhang Ke , Li Lei , Wu Jinhuan , Yuan Jian , Li Qi
Published: October 2019

DEAD box RNA helicase 17 (DDX17) is a transcriptional regulator of several transcription factors, which is more appreciated than its role in RNA metabolism. However, prognostic value and biofunction of DDX17 in HCC remain unclear. Illuminating the mechanism underlying the regulating HCC progression by DDX17 may contribute to therapeutic strategies. In our study, we report for the first time that DDX17 was overexpressed in HCC specimens by using The Cancer Genome Atlas (TCGA) and immunohistochemistry (IHC) and correlated to clinical pathological characteristics and patients’ survival. In vitro, DDX17 was ascertained to alter HCC migratory and invasive capacities after overexpression and knockdown in HCC cell lines. Moreover, by performing co-immunoprecipitation (Co-IP) and GST-pull down assay, the physical association between DDX17 and Klf4 was discovered and validated. Additionally, DDX17 could modulate expressions of Klf4 target genes including E-cadherin, MMP2 by inhibiting the promoter activity. The potent correlation between DDX17 and Klf4 target gene expressions was further appraised by a same set of 30 HCC tissues. Besides, we discovered that DDX17 could not deploy its function in regulating Klf4 target gene expressions and HCC progression in Klf4-depletion condition. Intriguingly, DDX17 failed to interact with Klf4 once the zinc-finger domain was deleted and inhibited the binding of Klf4 on MMP-2 promoter. Collectively, our study enucleates novel mechanism of DDX17-mediated oncogenesis by suppressing the transcriptional activity of Klf4 thus is likely to be a therapeutic target in HCC.
Enhancing dynamic actuation performance of dielectric elastomer actuators by tuning viscoelastic effects with polar crosslinking
Authors: Tan Matthew Wei Ming , Thangavel Gurunathan , Lee Pooi See
Published: October 2019

Dielectric elastomer actuators (DEAs) have shown great potential in the field of robotics, energy harvesting, or haptics for wearables. However, existing DEA materials typically require prestretching and exhibit time-dependent deformations due to their inherent viscoelastic properties. In this work, we address these issues by designing and synthesizing a polyurethane acrylate (PUA) DEA copolymerized with a polar crosslinker, polyethylene glycol diacrylate (PEGDA), to reduce viscoelastic effects through chemical crosslinking. We realized a buckling-mode actuator that displays out-of-plane deformations triggered by an electric field without the need for prestretching. Copolymerization with PEGDA showed improved dynamic response actuation performances compared to pristine PUA, wherein the former reached 90% of its maximum actuation in <1 s. In addition, precise and stable actuation was achieved, reducing viscoelastic drifts to a negligible amount. Despite the higher elastic modulus of the DEA incurred by the chemical crosslinks, the polar groups present in the PEGDA comonomer effectively increased the dielectric constant. As such, a higher area strain was achieved in comparison to that exhibited by low viscoelastic elastomers such as silicone. By eliminating the need for prestretching, rigid components can be avoided, thereby enabling greater prospects for the integration of fast response and stable DEAs into soft bodies.
Occurrence and repair of alkylating stress in the intracellular pathogen Brucella abortus
Authors: Poncin Katy , Roba Agnès , Jimmidi Ravikumar , Potemberg Georges , Fioravanti Antonella , Francis Nayla , Willemart Kévin , Zeippen Nicolas , Machelart Arnaud , Biondi Emanuele G. , Muraille Eric , Vincent Stéphane P. , De Bolle Xavier
Published: October 2019

It is assumed that intracellular pathogenic bacteria have to cope with DNA alkylating stress within host cells. Here we use single-cell reporter systems to show that the pathogen Brucella abortus does encounter alkylating stress during the first hours of macrophage infection. Genes encoding direct repair and base-excision repair pathways are required by B. abortus to face this stress in vitro and in a mouse infection model. Among these genes, ogt is found to be under the control of the conserved cell-cycle transcription factor GcrA. Our results highlight that the control of DNA repair in B. abortus displays distinct features that are not present in model organisms such as Escherichia coli.
Genetic mapping and evolutionary analysis of human-expanded cognitive networks
Authors: Wei Yongbin , de Lange Siemon C. , Scholtens Lianne H. , Watanabe Kyoko , Ardesch Dirk Jan , Jansen Philip R. , Savage Jeanne E. , Li Longchuan , Preuss Todd M. , Rilling James K. , Posthuma Danielle , van den Heuvel Martijn P.
Published: October 2019

Cognitive brain networks such as the default-mode network (DMN), frontoparietal network, and salience network, are key functional networks of the human brain. Here we show that the rapid evolutionary cortical expansion of cognitive networks in the human brain, and most pronounced the DMN, runs parallel with high expression of human-accelerated genes (HAR genes). Using comparative transcriptomics analysis, we present that HAR genes are differentially more expressed in higher-order cognitive networks in humans compared to chimpanzees and macaques and that genes with high expression in the DMN are involved in synapse and dendrite formation. Moreover, HAR and DMN genes show significant associations with individual variations in DMN functional activity, intelligence, sociability, and mental conditions such as schizophrenia and autism. Our results suggest that the expansion of higher-order functional networks subserving increasing cognitive properties has been an important locus of genetic changes in recent human brain evolution.
Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration
Authors: Menon Madhvi , Mohammadi Shahin , Davila-Velderrain Jose , Goods Brittany A. , Cadwell Tanina D. , Xing Yu , Stemmer-Rachamimov Anat , Shalek Alex K. , Love John Christopher , Kellis Manolis , Hafler Brian P.
Published: October 2019

Genome-wide association studies (GWAS) have identified genetic variants associated with age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. However, it has been challenging to identify the cell types associated with AMD given the genetic complexity of the disease. Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) of human retinas using two independent platforms, and report the first single-cell transcriptomic atlas of the human retina. Using a multi-resolution network-based analysis, we identify all major retinal cell types, and their corresponding gene expression signatures. Heterogeneity is observed within macroglia, suggesting that human retinal glia are more diverse than previously thought. Finally, GWAS-based enrichment analysis identifies glia, vascular cells, and cone photoreceptors to be associated with the risk of AMD. These data provide a detailed analysis of the human retina, and show how scRNA-seq can provide insight into cell types involved in complex, inflammatory genetic diseases.
Extreme nonlinear strong-field photoemission from carbon nanotubes
Authors: Li Chi , Chen Ke , Guan Mengxue , Wang Xiaowei , Zhou Xu , Zhai Feng , Dai Jiayu , Li Zhenjun , Sun Zhipei , Meng Sheng , Liu Kaihui , Dai Qing
Published: October 2019

Strong-field photoemission produces attosecond (10−18 s) electron pulses that are synchronized to the waveform of the incident light. This nonlinear photoemission lies at the heart of current attosecond technologies. Here we report a new nonlinear photoemission behaviour—the nonlinearity in strong-field regime sharply increases (approaching 40th power-law scaling), making use of sub-nanometric carbon nanotubes and 800 nm pulses. As a result, the carrier-envelope phase sensitive photoemission current shows a greatly improved modulation depth of up to 100% (with a total modulation current up to 2 nA). The calculations reveal that the behaviour is an interplay of valence band optical-field emission with charge interaction, and the nonlinear dynamics can be tunable by changing the bandgap of carbon nanotubes. The extreme nonlinear photoemission offers a new means of producing extreme temporal-spatial resolved electron pulses, and provides a new design philosophy for attosecond electronics and photonics.
Fungal-bacterial diversity and microbiome complexity predict ecosystem functioning
Authors: Wagg Cameron , Schlaeppi Klaus , Banerjee Samiran , Kuramae Eiko E. , van der Heijden Marcel G. A.
Published: October 2019

The soil microbiome is highly diverse and comprises up to one quarter of Earth’s diversity. Yet, how such a diverse and functionally complex microbiome influences ecosystem functioning remains unclear. Here we manipulated the soil microbiome in experimental grassland ecosystems and observed that microbiome diversity and microbial network complexity positively influenced multiple ecosystem functions related to nutrient cycling (e.g. multifunctionality). Grassland microcosms with poorly developed microbial networks and reduced microbial richness had the lowest multifunctionality due to fewer taxa present that support the same function (redundancy) and lower diversity of taxa that support different functions (reduced  functional uniqueness). Moreover, different microbial taxa explained different ecosystem functions pointing to the significance of functional diversity in microbial communities. These findings indicate the importance of microbial interactions within and among fungal and bacterial communities for enhancing ecosystem performance and demonstrate that the extinction of complex ecological associations belowground can impair ecosystem functioning.
A general synthesis approach for amorphous noble metal nanosheets
Authors: Wu Geng , Zheng Xusheng , Cui Peixin , Jiang Hongyu , Wang Xiaoqian , Qu Yunteng , Chen Wenxing , Lin Yue , Li Hai , Han Xiao , Hu Yanmin , Liu Peigen , Zhang Qinghua , Ge Jingjie , Yao Yancai , Sun Rongbo , Wu Yuen , Gu Lin , Hong Xun , Li Yadong
Published: October 2019

Noble metal nanomaterials have been widely used as catalysts. Common techniques for the synthesis of noble metal often result in crystalline nanostructures. The synthesis of amorphous noble metal nanostructures remains a substantial challenge. We present a general route for preparing dozens of different amorphous noble metal nanosheets with thickness less than 10 nm by directly annealing the mixture of metal acetylacetonate and alkali salts. Tuning atom arrangement of the noble metals enables to optimize their catalytic properties. Amorphous Ir nanosheets exhibit a superior performance for oxygen evolution reaction under acidic media, achieving 2.5-fold, 17.6-fold improvement in mass activity (at 1.53 V vs. reversible hydrogen electrode) over crystalline Ir nanosheets and commercial IrO2 catalyst, respectively. In situ X-ray absorption fine structure spectra indicate the valance state of Ir increased to less than + 4 during the oxygen evolution reaction process and recover to its initial state after the reaction.
Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits
Authors: Chakraborty Mahul , Emerson J. J. , Macdonald Stuart J. , Long Anthony D.
Published: October 2019

It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. Here we identified more than 20,000 euchromatic SVs from 14Drosophila melanogastergenome assemblies, of which ~40% are invisible to high specificity short-read genotyping approaches. SVs are common, with 31.5% of diploid individuals harboring a SV in genes larger than 5kb, and 24% harboring multiple SVs in genes larger than 10kb. SV minor allele frequencies are rarer than amino acid polymorphisms, suggesting that SVs are more deleterious. We show that a number of functionally important genes harbor previously hidden structural variants likely to affect complex phenotypes. Furthermore, SVs are overrepresented in candidate genes associated with quantitative trait loci mapped using the Drosophila Synthetic Population Resource. We conclude that SVs are ubiquitous, frequently constitute a heterogeneous allelic series, and can act as rare alleles of large effect.
Feature integration within discrete time windows
Authors: Drissi-Daoudi Leila , Doerig Adrien , Herzog Michael H.
Published: October 2019

Sensory information must be integrated over time to perceive, for example, motion and melodies. Here, to study temporal integration, we used the sequential metacontrast paradigm in which two expanding streams of lines are presented. When a line in one stream is offset observers perceive all other lines to be offset too, even though they are straight. When more lines are offset the offsets integrate mandatorily, i.e., observers cannot report the individual offsets. We show that mandatory integration lasts for up to 450 ms, depending on the observer. Importantly, integration occurs only when offsets are presented within a discrete window of time. Even stimuli that are in close spatio-temporal proximity do not integrate if they are in different windows. A window of integration starts with stimulus onset and integration in the next window has similar characteristics. We present a two-stage computational model based on discrete time windows that captures these effects.
Reverse diauxie phenotype in Pseudomonas aeruginosa biofilm revealed by exometabolomics and label-free proteomics
Authors: Yung Yeni P. , McGill S. Lee , Chen Hui , Park Heejoon , Carlson Ross P. , Hanley Luke
Published: October 2019

Microorganisms enhance fitness by prioritizing catabolism of available carbon sources using a process known as carbon catabolite repression (CCR). Planktonically grown Pseudomonas aeruginosa is known to prioritize the consumption of organic acids including lactic acid over catabolism of glucose using a CCR strategy termed “reverse diauxie.” P. aeruginosa is an opportunistic pathogen with well-documented biofilm phenotypes that are distinct from its planktonic phenotypes. Reverse diauxie has been described in planktonic cultures, but it has not been documented explicitly in P. aeruginosa biofilms. Here a combination of exometabolomics and label-free proteomics was used to analyze planktonic and biofilm phenotypes for reverse diauxie. P. aeruginosa biofilm cultures preferentially consumed lactic acid over glucose, and in addition, the cultures catabolized the substrates completely and did not exhibit the acetate secreting “overflow” metabolism that is typical of many model microorganisms. The biofilm phenotype was enabled by changes in protein abundances, including lactate dehydrogenase, fumarate hydratase, GTP cyclohydrolase, L-ornithine N(5)-monooxygenase, and superoxide dismutase. These results are noteworthy because reverse diauxie-mediated catabolism of organic acids necessitates a terminal electron acceptor like O2, which is typically in low supply in biofilms due to diffusion limitation. Label-free proteomics identified dozens of proteins associated with biofilm formation including 16 that have not been previously reported, highlighting both the advantages of the methodology utilized here and the complexity of the proteomic adaptation for P. aeruginosa biofilms. Documenting the reverse diauxic phenotype in P. aeruginosa biofilms is foundational for understanding cellular nutrient and energy fluxes, which ultimately control growth and virulence.
Insights into flagellar function and mechanism from the squid–vibrio symbiosis
Authors: Aschtgen Marie-Stephanie , Brennan Caitlin A. , Nikolakakis Kiel , Cohen Stephanie , McFall-Ngai Margaret , Ruby Edward G.
Published: October 2019

Flagella are essential and multifunctional nanomachines that not only move symbionts towards their tissue colonization site, but also play multiple roles in communicating with the host. Thus, untangling the activities of flagella in reaching, interacting, and signaling the host, as well as in biofilm formation and the establishment of a persistent colonization, is a complex problem. The squid–vibrio system offers a unique model to study the many ways that bacterial flagella can influence a beneficial association and, generally, other bacteria–host interactions.Vibrio fischeriis a bioluminescent bacterium that colonizes the Hawaiian bobtail squid,Euprymna scolopes. Over the last 15 years, the structure, assembly, and functions ofV. fischeriflagella, including not only motility and chemotaxis, but also biofilm formation and symbiotic signaling, have been revealed. Here we discuss these discoveries in the perspective of other host–bacteria interactions.
Wnt5a induces ROR1 to recruit cortactin to promote breast-cancer migration and metastasis
Authors: Hasan Md Kamrul , Widhopf George F. , Zhang Suping , Lam Sharon M. , Shen Zhouxin , Briggs Steven P. , Parker Barbara A. , Kipps Thomas J.
Published: October 2019

ROR1 is a conserved oncoembryonic surface protein expressed in breast cancer. Here we report that ROR1 associates with cortactin in primary breast-cancer cells or in MCF7 transfected to express ROR1. Wnt5a also induced ROR1-dependent tyrosine phosphorylation of cortactin (Y421), which recruited ARHGEF1 to activate RhoA and promote breast-cancer-cell migration; such effects could be inhibited by cirmtuzumab, a humanized mAb specific for ROR1. Furthermore, treatment of mice bearing breast-cancer xenograft with cirmtuzumab inhibited cortactin phosphorylation in vivo and impaired metastatic development. We established that the proline at 841 of ROR1 was required for it to recruit cortactin and ARHGEF1, activate RhoA, and enhance breast-cancer-cell migration in vitro or development of metastases in vivo. Collectively, these studies demonstrate that the interaction of ROR1 with cortactin plays an important role in breast-cancer-cell migration and metastasis.
Environmental transcriptomes of invasive dreissena, a model species in ecotoxicology and invasion biology
Authors: Péden Romain , Poupin Pascal , Sohm Bénédicte , Flayac Justine , Giambérini Laure , Klopp Christophe , Louis Fanny , Pain-Devin Sandrine , Potet Marine , Serre Rémy-Félix , Devin Simon
Published: October 2019

Dreissenids are established model species for ecological and ecotoxicological studies, since they are sessile and filter feeder organisms and reflect in situ freshwater quality. Despite this strong interest for hydrosystem biomonitoring, omics data are still scarce. In the present study, we achieved full de novo assembly transcriptomes of digestive glands to gain insight into Dreissena polymorpha and D. rostriformis bugensis molecular knowledge. Transcriptomes were obtained by Illumina RNA sequencing of seventy-nine organisms issued from fifteen populations inhabiting sites that exhibits multiple freshwater contamination levels and different hydrosystem topographies (open or closed systems). Based on a recent de novo assembly algorithm, we carried out a complete, quality-checked and annotated transcriptomes. The power of the present study lies in the completeness of transcriptomes gathering multipopulational organisms sequencing and its full availability through an open access interface that gives a friendly and ready-to-use access to data. The use of such data for proteogenomic and targeted biological pathway investigations purpose is promising as they are first full transcriptomes for this two Dreissena species.
Gas Diffusion Electrodes on the Electrosynthesis of Controllable Iron Oxide Nanoparticles
Authors: Prato Rafael A. , Van Vught Vincent , Eggermont Sam , Pozo Guillermo , Marin Pilar , Fransaer Jan , Dominguez-Benetton Xochitl
Published: October 2019

The electrosynthesis of iron oxide nanoparticles offers a green route, with significant energy and environmental advantages. Yet, this is mostly restricted by the oxygen solubility in the electrolyte. Gas-diffusion electrodes (GDEs) can be used to overcome that limitation, but so far they not been explored for nanoparticle synthesis. Here, we develop a fast, environmentally-friendly, room temperature electrosynthesis route for iron oxide nanocrystals, which we term gas-diffusion electrocrystallization (GDEx). A GDE is used to generate oxidants and hydroxide in-situ, enabling the oxidative synthesis of a single iron salt (e.g., FeCl2) into nanoparticles. Oxygen is reduced to reactive oxygen species, triggering the controlled oxidation of Fe2+ to Fe3+, forming Fe3−xO4−x (0 ≤ x ≤ 1). The stoichiometry and lattice parameter of the resulting oxides can be controlled and predictively modelled, resulting in highly-defective, strain-heavy nanoparticles. The size of the nanocrystals can be tuned from 5 nm to 20 nm, with a large saturation magnetization range (23 to 73 A m2 kg−1), as well as minimal coercivity (~1 kA m−1). Using only air, NaCl, and FeCl2, a biocompatible approach is achieved, besides a remarkable level of control over key parameters, with a view on minimizing the addition of chemicals for enhanced production and applications.
Highly Plasmonic Titanium Nitride by Room-Temperature Sputtering
Authors: Chang Chun-Chieh , Nogan John , Yang Zu-Po , Kort-Kamp Wilton J. M. , Ross Willard , Luk Ting S. , Dalvit Diego A. R. , Azad Abul K. , Chen Hou-Tong
Published: October 2019

Titanium nitride (TiN) has recently emerged as an attractive alternative material for plasmonics. However, the typical high-temperature deposition of plasmonic TiN using either sputtering or atomic layer deposition has greatly limited its potential applications and prevented its integration into existing CMOS device architectures. Here, we demonstrate highly plasmonic TiN thin films and nanostructures by a room-temperature, low-power, and bias-free reactive sputtering process. We investigate the optical properties of the TiN films and their dependence on the sputtering conditions and substrate materials. We find that our TiN possesses one of the largest negative values of the real part of the dielectric function as compared to all other plasmonic TiN films reported to date. Two-dimensional periodic arrays of TiN nanodisks are then fabricated, from which we validate that strong plasmonic resonances are supported. Our room-temperature deposition process can allow for fabricating complex plasmonic TiN nanostructures and be integrated into the fabrication of existing CMOS-based photonic devices to enhance their performance and functionalities.
Pop-in behavior and elastic-to-plastic transition of polycrystalline pure iron during sharp nanoindentation
Authors: Pöhl Fabian
Published: October 2019

This study analyzes the elastic-to-plastic transition during nanoindentation of polycrystalline iron. We conduct nanoindentation (Berkovich indenter) experiments and electron backscatter diffraction analysis to investigate the initiation of plasticity by the appearance of the pop-in phenomenon in the loading curves. Numerous load–displacement curves are statistically analyzed to identify the occurrence of pop-ins. A first pop-in can result from plasticity initiation caused by homogeneous dislocation nucleation and requires shear stresses in the range of the theoretical strength of a defect-free iron crystal. The results also show that plasticity initiation in volumes with preexisting dislocations is significantly affected by small amounts of interstitially dissolved atoms (such as carbon) that are segregated into the stress fields of dislocations, impeding their mobility. Another strong influence on the pop-in behavior is grain boundaries, which can lead to large pop-ins at relatively high indentation loads. The pop-in behavior appears to be a statistical process affected by interstitial atoms, dislocation density, grain boundaries, and surface roughness. No effect of the crystallographic orientation on the pop-in behavior can be observed.
Integrin α11 cytoplasmic tail is required for FAK activation to initiate 3D cell invasion and ERK-mediated cell proliferation
Authors: Erusappan Pugazendhi , Alam Jahedul , Lu Ning , Zeltz Cédric , Gullberg Donald
Published: October 2019

Integrin α11β1 is a collagen-binding integrin, which is receiving increasing attention in the context of wound healing and fibrosis. Although α11β1 integrin displays similar collagen specificity to α2β1 integrin, both integrins have distinct in vivo functions. In this context, the contribution of α11 subunit cytoplasmic tail interactions to diverse molecular signals and biological functions is largely unknown. In the current study, we have deleted the α11 cytoplasmic tail and studied the effect of this deletion on α11 integrin function. Compared to wild-type cells, C2C12 cells expressing tail-less α11 attached normally to collagen I, but formed fewer focal contacts. α11-tail-less cells furthermore displayed a reduced capacity to invade and reorganize a 3D collagen matrix and to proliferate. Analysis of cell signaling showed that FAK and ERK phosphorylation was reduced in cells expressing tail-less α11. Inhibition of ERK and FAK activation decreased α11-mediated cell proliferation, whereas α11-mediated cell invasion was FAK-dependent and occurred independently of ERK signaling. In summary, our data demonstrate that the integrin α11 cytoplasmic tail plays a central role in α11 integrin-specific functions, including FAK-dependent ERK activation to promote cell proliferation.
A new approach to study the Zeno effect for a macroscopic quantum system under frequent interactions with a harmonic environment
Authors: Ghasemi Fatemeh , Shafiee Afshin
Published: October 2019

Quantum Zeno and anti-Zeno behaviors of a two-level macroscopic quantum system in interaction with a harmonic environment are studied using the perturbation theory. The system-environment interactions are applied in a successive and step-by-step way. A new expression for the probability of surviving the macrosystem in its initial state, after the Nth interaction step, is derived through a different method of calculation. It is shown that multiple transitions between Zeno and anti-Zeno behaviors can be found in our approach. We have shown that in addition to the environmental parameters like the Ohmicity, the macroscopic trait of the system also has a notable effect on the decay rate Γ(τ). Moreover, we have investigated how the decay rate Γ(τ) varies as the parameter of the macroscopicity of the system $$\tilde{{\boldsymbol{h}}}$$

h
˜

changes continuously in a given domain.
Millimeter-wave pulsed heating in vitro: cell mortality and heat shock response
Authors: Orlacchio Rosa , Le Page Yann , Le Dréan Yves , Le Guével Rémy , Sauleau Ronan , Alekseev Stanislav , Zhadobov Maxim
Published: October 2019

Millimeter wave (MMW)-induced heating represents a promising alternative for non-invasive hyperthermia of superficial skin cancer, such as melanoma. Pulsed MMW-induced heating of tumors allows for reaching high peak temperatures without overheating surrounding tissues. Herein, for the first time, we evaluate apoptotic and heat shock responses of melanoma cells exposed in vitro to continuous (CW) or pulsed-wave (PW) amplitude-modulated MMW at 58.4 GHz with the same average temperature rise. Using an ad hoc exposure system, we generated 90 min pulse train with 1.5 s pulse duration, period of 20 s, amplitude of 10 °C, and steady-state temperature at the level of cells of 49.2 °C. The activation of Caspase-3 and phosphorylation of HSP27 were investigated using fluorescence microscopy to monitor the spatial variation of cellular response. Our results demonstrate that, under the considered exposure conditions, Caspase-3 activation was almost 5 times greater following PW exposure compared to CW. The relationship between the PW-induced cellular response and SAR-dependent temperature rise was non-linear. Phosphorylation of HSP27 was 58% stronger for PW compared to CW. It exhibits a plateau for the peak temperature ranging from 47.7 to 49.2 °C. Our results provide an insight into understanding of the cellular response to MMW-induced pulsed heating.
Synthesis of Hollow Pt-Ni Nanoboxes for Highly Efficient Methanol Oxidation
Authors: Jamil Rabia , Sohail Manzar , Baig Nadeem , Ansari Muhammad S. , Ahmed Riaz
Published: October 2019

In direct methanol fuel cell technology, highly stable electrochemical catalysts are critically important for their practical utilization at the commercial scale. In this study, sub ~10 nm hollow Pt-Ni (1:1 at. ratio) nanoboxes supported on functionalized Vulcan carbon (Pt-Ni/C-R2) were synthesized through a facile method for the efficient electrooxidation of methanol. Two reaction procedures, namely, a simultaneous reduction and a modified sequential reduction method using a reverse microemulsion (RME) method, were adopted to synthesize solid Pt-Ni NPs and hollow nanoboxes, respectively. To correlate the alloy composition and surface structure with the enhanced catalytic activity, the results were compared with the nanocatalyst synthesized using a conventional NaBH4reduction method. The calculated electroactive surface area for the Pt-Ni/C-R2 nanoboxes was 190.8 m2.g−1, which is significantly higher compared to that of the Pt-Ni nanocatalyst (96.4 m2.g−1) synthesized by a conventional reduction method. Hollow nanoboxes showed 34% and 44% increases in mass activity and rate of methanol oxidation reaction, respectively, compared to solid NPs. These results support the nanoreactor confinement effect of the hollow nanoboxes. The experimental results were supported by Density Functional Theory (DFT) studies, which revealed that the lowest CO poisoning of the Pt1Ni1catalyst among all Ptm-Ninmixing ratios may account for the enhanced methanol oxidation. The synthesized hollow Pt-Ni/C (R2) nanoboxes may prove to be a valuable and highly efficient catalysts for the electrochemical oxidation of methanol due to their low cost, numerous catalytically active sites, low carbon monoxide poisoning, large electroactive surface area and long-term stability.
Association of Fok1 VDR polymorphism with Vitamin D and its associated molecules in pulmonary tuberculosis patients and their household contacts
Authors: Panda Sudhasini , Tiwari Ambrish , Luthra Kalpana , Sharma S. K. , Singh Archana
Published: October 2019

Status of Fok I VDR polymorphism along with vitamin D, Vitamin D receptor (VDR), and cathelicidin levels in Tuberculosis (TB) patients compared to household contacts and implication of these findings in susceptibility to TB is not known. 150 active TB patients, 150 household contacts and 150 healthy controls were recruited from North Indian population. Fok1 VDR polymorphism was studied by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).VDR mRNA and protein levels were studied using quantitative real time PCR (q rt PCR) and enzyme linked immunosorbent assay (ELISA) respectively. Cathelicidin and Vitamin D levels were measured using ELISA and chemiluminescence immunoassay (CLIA) respectively. Significant association was found between Fok1 polymorphism and susceptibility to TB (P < 0.0005). VDR mRNA, VDR protein and vitamin D levels were significantly lower in active TB group when compared to household contacts and healthy controls (P < 0.0001, 0.0001 and 0.0005 respectively). Cathelicidin levels were higher in active TB patients compared to other groups (P < 0.0001). Expression of VDR and cathelicidin was significantly higher among ‘FF’ genotypes of VDR (more active form of VDR) compared to ‘ff’ genotype (less active form of VDR). ‘f’ allele was associated with increased susceptibility to TB. Higher frequency of ‘F’ allele, increased VDR expression along with increased vitamin D levels in household contacts compared to active TB group might be responsible for protection against active TB.
A Recent Systematic Increase in Vapor Pressure Deficit over Tropical South America
Authors: Barkhordarian Armineh , Saatchi Sassan S. , Behrangi Ali , Loikith Paul C. , Mechoso Carlos R.
Published: October 2019

We show a recent increasing trend in Vapor Pressure Deficit (VPD) over tropical South America in dry months with values well beyond the range of trends due to natural variability of the climate system defined in both the undisturbed Preindustrial climate and the climate over 850–1850 perturbed with natural external forcing. This trend is systematic in the southeast Amazon but driven by episodic droughts (2005, 2010, 2015) in the northwest, with the highest recoded VPD since 1979 for the 2015 drought. The univariant detection analysis shows that the observed increase in VPD cannot be explained by greenhouse-gas-induced (GHG) radiative warming alone. The bivariate attribution analysis demonstrates that forcing by elevated GHG levels and biomass burning aerosols are attributed as key causes for the observed VPD increase. We further show that There is a negative trend in evaporative fraction in the southeast Amazon, where lack of atmospheric moisture, reduced precipitation together with higher incoming solar radiation (~7% decade−1 cloud-cover reduction) influences the partitioning of surface energy fluxes towards less evapotranspiration. The VPD increase combined with the decrease in evaporative fraction are the first indications of positive climate feedback mechanisms, which we show that will continue and intensify in the course of unfolding anthropogenic climate change.
Surface Modification by Media Organics Reduces the Bacterio-toxicity of Cupric Oxide Nanoparticle against Escherichia coli
Authors: Chakraborty Ruchira , Basu Tarakdas
Published: October 2019

Prevalence of antibiotic-resistant bacteria demands alternatives to antibiotics. Copper-based nanoparticles with a high antibacterial property may be a solution to the problem. It is, therefore, important to understand the mode of antibacterial action of the nanoparticles (NPs). Despite reports on induction of reactive oxygen species (ROS) in bacteria by copper and copper-oxide nanoparticles and involvement of such ROS in cell killing, it is still unclear (a) if surface modification of the nanoparticles by media organics has any role on their antibacterial potency and (b) whether the bactericidal effects of these NPs are ‘particle-specific’ or ‘ion-specific’ in nature. We address these issues for cupric oxide nanoparticle (CuO-NP) in this study. Instead of nutrient medium, whenE. colibacterial cells were suspended in saline (0.9% NaCl), CuO-NP had a more anti-bacterial effect, with MBC (minimum bactericidal concentration) value of 6 µg/mL, than in nutrient medium with MBC value of 160 µg/mL. Moreover, the lysine-modified CuO-NP in saline had MBC at 130 µg/mL. Thus, unmodified CuO-NP was more efficient killer than modified one. Our finding further revealed that in saline;CuO-NP had ‘particle-specific’ antibacterial effect through generation of ROS and consequent oxidative damage by lipid peroxidation, protein oxidation and DNA degradation in cells.
Anomalous Nernst effect in stressed magnetostrictive film grown onto flexible substrate
Authors: Melo Acácio Silveira , Oliveira Alexandre Barbosa de , Chesman Carlos , Della Pace Rafael Domingues , Bohn Felipe , Correa Marcio Assolin
Published: October 2019

The anomalous Nernst effect in nanostructured magnetic materials is a key phenomenon to optimally control and employ the internal energy dissipated in electronic devices, being dependent on, for instance, the magnetic anisotropy of the active element. Thereby, here, we report a theoretical and experimental investigation of the magnetic properties and anomalous Nernst effect in a flexible magnetostrictive film with induced uniaxial magnetic anisotropy and under external stress. Specifically, we calculate the magnetization behavior and the thermoelectric voltage response from a theoretical approach for a planar geometry, with magnetic free energy density that takes into account the induced uniaxial and magnetoelastic anisotropy contributions. Experimentally, we verify modifications of the effective magnetic anisotropy by changing the external stress, and explore the anomalous Nernst effect, a powerful tool to investigate the magnetic properties of magnetostrictive materials. We find quantitative agreement between experiment and numerical calculations, thus elucidating the magnetic behavior and thermoelectric voltage response. Besides, we provide evidence to confirm the validity of the theoretical approach to describe the magnetic properties and anomalous Nernst effect in ferromagnetic magnetostrictive films having uniaxial magnetic anisotropy and submitted to external stress. Hence, the results place flexible magnetostrictive systems as promising candidates for active elements in functionalized touch electronic devices.
Adipocyte browning and resistance to obesity in mice is induced by expression of ATF3
Authors: Cheng Ching-Feng , Ku Hui-Chen , Cheng Jing-Jy , Chao Shi-Wei , Li Hsiao-Fen , Lai Pei-Fang , Chang Che-Chang , Don Ming-Jaw , Chen Hsi-Hsien , Lin Heng
Published: October 2019

Billions of people have obesity-related metabolic syndromes such as diabetes and hyperlipidemia. Promoting the browning of white adipose tissue has been suggested as a potential strategy, but a drug still needs to be identified. Here, genetic deletion of activating transcription factor 3 (ATF3−/−) in mice under a high-fat diet (HFD) resulted in obesity and insulin resistance, which was abrogated by virus-mediated ATF3 restoration. ST32da, a synthetic ATF3 inducer isolated from Salvia miltiorrhiza, promoted ATF3 expression to downregulate adipokine genes and induce adipocyte browning by suppressing the carbohydrate-responsive element-binding protein–stearoyl-CoA desaturase-1 axis. Furthermore, ST32da increased white adipose tissue browning and reduced lipogenesis in HFD-induced obese mice. The anti-obesity efficacy of oral ST32da administration was similar to that of the clinical drug orlistat. Our study identified the ATF3 inducer ST32da as a promising therapeutic drug for treating diet-induced obesity and related metabolic disorders.