bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIX-01294 sensitizes renal cancer Caki cells to TRAIL-induced apoptosis through downregulation of survivin expression and upregulation of DR5 expression
Authors: Woo Seon Min , Seo Seung Un , Min Kyoung-Jin , Kwon Taeg Kyu 
Published: February 2018

AbstractBIX-01294 (BIX), a G9a histone methyltransferase inhibitor, has been reported for its anti-proliferative and anticancer activities against various cancer cell lines. In this study, we investigated whether BIX could sensitize TRAIL-mediated apoptosis in various cancer cells. Combined treatment with BIX and TRAIL markedly induced apoptosis in human renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MCF-7), and lung carcinoma (A549) cells. In contrast, BIX and TRAIL co-treatment did not induce apoptosis in normal cells, specifically mouse kidney cell (TCMK-1) and human skin fibroblast (HSF). BIX downregulated protein expression levels of XIAP and survivin at the post-translational level. Overexpression of survivin markedly blocked combined BIX and TRAIL treatment-induced apoptosis, but XIAP had no effect. Furthermore, BIX induced upregulation of DR5 expression at the transcriptional levels, and knockdown of DR5 expression using small interfering RNAs (siRNAs) markedly attenuated BIX and TRAIL-induced apoptosis. Interestingly, siRNA-mediated G9a histone methyltransferase knockdown also enhanced TRAIL-induced apoptosis in Caki cells. However, knockdown of G9a did not change expression levels of XIAP, survivin, and DR5. Therefore, BIX-mediated TRAIL sensitization was independent of histone methyltransferase G9a activity. Taken together, these results suggest that BIX facilitates TRAIL-mediated apoptosis via downregulation of survivin and upregulation of DR5 expression in renal carcinoma Caki cells.▶ BIX facilitates TRAIL-mediated apoptosis in human renal carcinoma Caki cells.▶ Downregulation of survivin contributes to BIX plus TRAIL-induced apoptosis.▶ Upregulation of DR5 is involved in BIX plus TRAIL-mediated apoptosis.▶ BIX-mediated TRAIL sensitization is independent of ROS production.
Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL
Authors: Kapadia Bandish , Nanaji Nahid M. , Bhalla Kavita , Bhandary Binny , Lapidus Rena , Beheshti Afshin , Evens Andrew M. , Gartenhaus Ronald B. 
Published: February 2018

AbstractAltered lipid metabolism and aberrant protein translation are strongly associated with cancerous outgrowth; however, the inter-regulation of these key processes is still underexplored in diffuse large B-cell lymphoma (DLBCL). Although fatty acid synthase (FASN) activity is reported to positively correlate with PI3K-Akt-mTOR pathway that can modulate protein synthesis, the precise impact of FASN inhibition on this process is still unknown. Herein, we demonstrate that attenuating FASN expression or its activity significantly reduces eIF4B (eukaryotic initiation factor 4B) levels and consequently overall protein translation. Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity. Employing both pharmacological and genetic approaches, we establish that FASN-induced PI3K-S6Kinase signaling phosphorylates USP11 enhancing its interaction with eIF4B and thereby promoting oncogenic translation.
EGFL7 reduces CNS inflammation in mouse
Authors: Larochelle Catherine , Uphaus Timo , Broux Bieke , Gowing Elizabeth , Paterka Magdalena , Michel Laure , Dudvarski Stankovic Nevenka , Bicker Frank , Lemaître Florent , Prat Alexandre , Schmidt Mirko H. H. , Zipp Frauke 
Published: February 2018

AbstractExtracellular matrix (ECM) proteins secreted by blood-brain barrier (BBB) endothelial cells (ECs) are implicated in cell trafficking. We discovered that the expression of ECM epidermal growth factor-like protein 7 (EGFL7) is increased in the CNS vasculature of patients with multiple sclerosis (MS), and in mice with experimental autoimmune encephalomyelitis (EAE). Perivascular CD4 T lymphocytes colocalize with ECM-bound EGFL7 in MS lesions. Human and mouse activated T cells upregulate EGFL7 ligand αvβ3 integrin and can adhere to EGFL7 through integrin αvβ3. EGFL7-knockout (KO) mice show earlier onset of EAE and increased brain and spinal cord parenchymal infiltration of T lymphocytes. Importantly, EC-restricted EGFL7-KO is associated with a similar EAE worsening. Finally, treatment with recombinant EGFL7 improves EAE, reduces MCAM expression, and tightens the BBB in mouse. Our data demonstrate that EGFL7 can limit CNS immune infiltration and may represent a novel therapeutic avenue in MS.
Gene-by-environment interactions in urban populations modulate risk phenotypes
Authors: Favé Marie-Julie , Lamaze Fabien C. , Soave David , Hodgkinson Alan , Gauvin Héloïse , Bruat Vanessa , Grenier Jean-Christophe , Gbeha Elias , Skead Kimberly , Smargiassi Audrey , Johnson Markey , Idaghdour Youssef , Awadalla Philip 
Published: February 2018

AbstractUncovering the interaction between genomes and the environment is a principal challenge of modern genomics and preventive medicine. While theoretical models are well defined, little is known of the G × E interactions in humans. We used an integrative approach to comprehensively assess the interactions between 1.6 million data points, encompassing a range of environmental exposures, health, and gene expression levels, coupled with whole-genome genetic variation. From ∼1000 individuals of a founder population in Quebec, we reveal a substantial impact of the environment on the transcriptome and clinical endophenotypes, overpowering that of genetic ancestry. Air pollution impacts gene expression and pathways affecting cardio-metabolic and respiratory traits, when controlling for genetic ancestry. Finally, we capture four expression quantitative trait loci that interact with the environment (air pollution). Our findings demonstrate how the local environment directly affects disease risk phenotypes and that genetic variation, including less common variants, can modulate individual’s response to environmental challenges.
Effect of friction on oxidative graphite intercalation and high-quality graphene formation
Authors: Seiler Steffen , Halbig Christian E. , Grote Fabian , Rietsch Philipp , Börrnert Felix , Kaiser Ute , Meyer Bernd , Eigler Siegfried 
Published: February 2018

AbstractOxidative wet-chemical delamination of graphene from graphite is expected to become a scalable production method. However, the formation process of the intermediate stage-1 graphite sulfate by sulfuric acid intercalation and its subsequent oxidation are poorly understood and lattice defect formation must be avoided. Here, we demonstrate film formation of micrometer-sized graphene flakes with lattice defects down to 0.02% and visualize the carbon lattice by transmission electron microscopy at atomic resolution. Interestingly, we find that only well-ordered, highly crystalline graphite delaminates into oxo-functionalized graphene, whereas other graphite grades do not form a proper stage-1 intercalate and revert back to graphite upon hydrolysis. Ab initio molecular dynamics simulations show that ideal stacking and electronic oxidation of the graphite layers significantly reduce the friction of the moving sulfuric acid molecules, thereby facilitating intercalation. Furthermore, the evaluation of the stability of oxo-species in graphite sulfate supports an oxidation mechanism that obviates intercalation of the oxidant.
The interdependence of excitation and inhibition for the control of dynamic breathing rhythms
Authors: Baertsch Nathan Andrew , Baertsch Hans Christopher , Ramirez Jan Marino 
Published: February 2018

AbstractThe preBötzinger Complex (preBötC), a medullary network critical for breathing, relies on excitatory interneurons to generate the inspiratory rhythm. Yet, half of preBötC neurons are inhibitory, and the role of inhibition in rhythmogenesis remains controversial. Using optogenetics and electrophysiology in vitro and in vivo, we demonstrate that the intrinsic excitability of excitatory neurons is reduced following large depolarizing inspiratory bursts. This refractory period limits the preBötC to very slow breathing frequencies. Inhibition integrated within the network is required to prevent overexcitation of preBötC neurons, thereby regulating the refractory period and allowing rapid breathing. In vivo, sensory feedback inhibition also regulates the refractory period, and in slowly breathing mice with sensory feedback removed, activity of inhibitory, but not excitatory, neurons restores breathing to physiological frequencies. We conclude that excitation and inhibition are interdependent for the breathing rhythm, because inhibition permits physiological preBötC bursting by controlling refractory properties of excitatory neurons.
Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes
Authors: Yang Cui-Ping , Li Xiaoyan , Wu Yong , Shen Qiushuo , Zeng Yong , Xiong Qiuxia , Wei Mengping , Chen Chunhui , Liu Jiewei , Huo Yongxia , Li Kaiqin , Xue Gui , Yao Yong-Gang , Zhang Chen , Li Ming , Chen Yongbin , Luo Xiong-Jian 
Published: February 2018

AbstractRecent genome-wide association studies (GWAS) have identified multiple risk loci that show strong associations with schizophrenia. However, pinpointing the potential causal genes at the reported loci remains a major challenge. Here we identify candidate causal genes for schizophrenia using an integrative genomic approach. Sherlock integrative analysis shows that ALMS1, GLT8D1, and CSNK2B are schizophrenia risk genes, which are validated using independent brain expression quantitative trait loci (eQTL) data and integrative analysis method (SMR). Consistently, gene expression analysis in schizophrenia cases and controls further supports the potential role of these three genes in the pathogenesis of schizophrenia. Finally, we show that GLT8D1 and CSNK2B knockdown promote the proliferation and inhibit the differentiation abilities of neural stem cells, and alter morphology and synaptic transmission of neurons. These convergent lines of evidence suggest that the ALMS1, CSNK2B, and GLT8D1 genes may be involved in pathophysiology of schizophrenia.
Superplastic nanoscale pore shaping by ion irradiation
Authors: Aramesh Morteza , Mayamei Yashar , Wolff Annalena , Ostrikov Kostya 
Published: February 2018

AbstractExposed to ionizing radiation, nanomaterials often undergo unusual transformations compared to their bulk form. However, atomic-level mechanisms of such transformations are largely unknown. This work visualizes and quantifies nanopore shrinkage in nanoporous alumina subjected to low-energy ion beams in a helium ion microscope. Mass transport in porous alumina is thus simultaneously induced and imaged with nanoscale precision, thereby relating nanoscale interactions to mesoscopic deformations. The interplay between chemical bonds, disorders, and ionization-induced transformations is analyzed. It is found that irradiation-induced diffusion is responsible for mass transport and that the ionization affects mobility of diffusive entities. The extraordinary room temperature superplasticity of the normally brittle alumina is discovered. These findings enable the effective manipulation of chemical bonds and structural order by nanoscale ion-matter interactions to produce mesoscopic structures with nanometer precision, such as ultra-high density arrays of sub-10-nm pores with or without the accompanying controlled plastic deformations.
Scalable on-chip quantum state tomography
Authors: Titchener James G. , Gräfe Markus , Heilmann René , Solntsev Alexander S. , Szameit Alexander , Sukhorukov Andrey A. 
Published: February 2018

AbstractQuantum information systems are on a path to vastly exceed the complexity of any classical device. The number of entangled qubits in quantum devices is rapidly increasing, and the information required to fully describe these systems scales exponentially with qubit number. This scaling is the key benefit of quantum systems, however it also presents a severe challenge. To characterize such systems typically requires an exponentially long sequence of different measurements, becoming highly resource demanding for large numbers of qubits. Here we propose and demonstrate a novel and scalable method for characterizing quantum systems based on expanding a multi-photon state to larger dimensionality. We establish that the complexity of this new measurement technique only scales linearly with the number of qubits, while providing a tomographically complete set of data without a need for reconfigurability. We experimentally demonstrate an integrated photonic chip capable of measuring two- and three-photon quantum states with statistical reconstruction fidelity of 99.71%.
A personalized, multiomics approach identifies genes involved in cardiac hypertrophy and heart failure
Authors: Santolini Marc , Romay Milagros C. , Yukhtman Clara L. , Rau Christoph D. , Ren Shuxun , Saucerman Jeffrey J. , Wang Jessica J. , Weiss James N. , Wang Yibin , Lusis Aldons J. , Karma Alain 
Published: February 2018

AbstractA traditional approach to investigate the genetic basis of complex diseases is to identify genes with a global change in expression between diseased and healthy individuals. However, population heterogeneity may undermine the effort to uncover genes with significant but individual contribution to the spectrum of disease phenotypes within a population. Here we investigate individual changes of gene expression when inducing hypertrophy and heart failure in 100 + strains of genetically distinct mice from the Hybrid Mouse Diversity Panel (HMDP). We find that genes whose expression fold-change correlates in a statistically significant way with the severity of the disease are either up or down-regulated across strains, and therefore missed by a traditional population-wide analysis of differential gene expression. Furthermore, those “fold-change” genes are enriched in human cardiac disease genes and form a dense co-regulated module strongly interacting with the cardiac hypertrophic signaling network in the human interactome. We validate our approach by showing that the knockdown of Hes1, predicted as a strong candidate, induces a dramatic reduction of hypertrophy by 80–90% in neonatal rat ventricular myocytes. Our results demonstrate that individualized approaches are crucial to identify genes underlying complex diseases as well as to develop personalized therapies.
Fe-oxide mineralogy of the Jiujiang red earth sediments and implications for Quaternary climate change, southern China
Authors: Yin Ke , Hong Hanlie , Algeo Thomas J. , Churchman Gordon Jock , Li Zhaohui , Zhu Zongmin , Fang Qian , Zhao Lulu , Wang Chaowen , Ji Kaipeng , Lei Weidong , Duan Zhenggang 
Published: February 2018

AbstractDiffuse reflectance spectrophotometry (DRS) is a new, fast, and reliable method to characterize Fe-oxides in soils. The Fe-oxide mineralogy of the Jiujiang red earth sediments was investigated using DRS to investigate the climate evolution of southern China since the mid-Pleistocene. The DRS results show that hematite/(hematite + goethite) ratios [Hm/(Hm + Gt)] exhibit an upward decreasing trend within the Jiujiang section, suggesting a gradual climate change from warm and humid in the middle Pleistocene to cooler and drier in the late Pleistocene. Upsection trends toward higher (orthoclase + plagioclase)/quartz ratios [(Or + Pl)/Q] and magnetic susceptibility values (χlf) support this inference, which accords with global climate trends at that time. However, higher-frequency climatic subcycles observed in loess sections of northern China are not evident in the Jiujiang records, indicating a relatively lower climate sensitivity of the red earth sediments in southern China.
Improving prediction of heart transplantation outcome using deep learning techniques
Authors: Medved Dennis , Ohlsson Mattias , Höglund Peter , Andersson Bodil , Nugues Pierre , Nilsson Johan 
Published: February 2018

AbstractThe primary objective of this study is to compare the accuracy of two risk models, International Heart Transplantation Survival Algorithm (IHTSA), developed using deep learning technique, and Index for Mortality Prediction After Cardiac Transplantation (IMPACT), to predict survival after heart transplantation. Data from adult heart transplanted patients between January 1997 to December 2011 were collected from the UNOS registry. The study included 27,860 heart transplantations, corresponding to 27,705 patients. The study cohorts were divided into patients transplanted before 2009 (derivation cohort) and from 2009 (test cohort). The receiver operating characteristic (ROC) values, for the validation cohort, computed for one-year mortality, were 0.654 (95% CI: 0.629–0.679) for IHTSA and 0.608 (0.583–0.634) for the IMPACT model. The discrimination reached a C-index for long-term survival of 0.627 (0.608–0.646) for IHTSA, compared with 0.584 (0.564–0.605) for the IMPACT model. These figures correspond to an error reduction of 12% for ROC and 10% for C-index by using deep learning technique. The predicted one-year mortality rates for were 12% and 22% for IHTSA and IMPACT, respectively, versus an actual mortality rate of 10%. The IHTSA model showed superior discriminatory power to predict one-year mortality and survival over time after heart transplantation compared to the IMPACT model.
MicroRNA Contents in Matrix Vesicles Produced by Growth Plate Chondrocytes are Cell Maturation Dependent
Authors: Lin Zhao , McClure Michael J. , Zhao Junjun , Ramey Allison N. , Asmussen Niels , Hyzy Sharon L. , Schwartz Zvi , Boyan Barbara D. 
Published: February 2018

AbstractChondrocytes at different maturation states in the growth plate produce matrix vesicles (MVs), membrane organelles found in the extracellular matrix, with a wide range of contents, such as matrix processing enzymes and receptors for hormones. We have shown that MVs harvested from growth zone (GC) chondrocyte cultures contain abundant small RNAs, including miRNAs. Here, we determined whether RNA also exists in MVs produced by less mature resting zone (RC) chondrocytes and, if so, whether it differs from the RNA in MVs produced by GC cells. Our results showed that RNA, small RNA specifically, was present in RC-MVs, and it was well-protected from RNase by the phospholipid membrane. A group of miRNAs was enriched in RC-MVs compared RC-cells, suggesting that miRNAs are selectively packaged into MVs. High throughput array and RNA sequencing showed that ~39% miRNAs were differentially expressed between RC-MVs and GC-MVs. Individual RT-qPCR also confirmed that miR-122-5p and miR-150-5p were expressed at significantly higher levels in RC-MVs compared to GC-MVs. This study showed that growth plate chondrocytes at different differentiation stages produce different MVs with different miRNA contents, further supporting extracellular vesicle miRNAs play a role as “matrisomes” that mediate the cell–cell communication in cartilage and bone development.
High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation
Authors: Sadnicka Anna , Stevenson Anna , Bhatia Kailash P. , Rothwell John C. , Edwards Mark J. , Galea Joseph M. 
Published: February 2018

AbstractFor the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted.
Cytoplasmic Transport Machinery of the SPF27 Homologue Num1 in Ustilago maydis
Authors: Zhou Lu , Obhof Theresa , Schneider Karina , Feldbrügge Michael , Nienhaus G. Ulrich , Kämper Jörg 
Published: February 2018

AbstractIn the phytopathogenic basidiomycete Ustilago maydis, the Num1 protein has a pivotal function in hyphal morphogenesis. Num1 functions as a core component of the spliceosome-associated Prp19/CDC5 complex (NTC). The interaction of Num1 with the kinesin motor Kin1 suggests a connection between a component of the splicing machinery and cytoplasmic trafficking processes. Previously it was shown that Num1 localizes predominantly in the nucleus; however, due to the diffraction-limited spatial resolution of conventional optical microscopy, it was not possible to attribute the localization to specific structures within the cytoplasm. We have now employed super-resolution localization microscopy to visualize Num1 in the cytoplasm by fusing it to a tandem dimeric Eos fluorescent protein (tdEosFP). The Num1 protein is localized within the cytoplasm with an enhanced density in the vicinity of microtubules. Num1 movement is found predominantly close to the nucleus. Movement is dependent on its interaction partner Kin1, but independent of Kin3. Our results provide strong evidence that, in addition to its involvement in splicing in the nucleus, Num1 has an additional functional role in the cytosol connected to the Kin1 motor protein.
Linear Micro-patterned Drug Eluting Balloon (LMDEB) for Enhanced Endovascular Drug Delivery
Authors: Lee KangJu , Lee Seul Gee , Jang Ilkwang , Park Seung Hyun , Yang Dasom , Seo Il Ho , Bong Sung-Kyung , An Duk Hwan , Lee Min Kwon , Jung In Kwon , Jang Yong Hoon , Kim Jung Sun , Ryu WonHyoung 
Published: February 2018

AbstractIn-stent restenosis (ISR) often occurs after applying drug eluting stents to the blood vessels suffering from atherosclerosis or thrombosis. For treatment of ISR, drug eluting balloons (DEB) have been developed to deliver anti-proliferative drugs to the lesions with ISR. However, there are still limitations of DEB such as low drug delivery efficiency and drug loss to blood flow. Although most researches have focused on alteration of drug formulation for more efficient drug delivery, there are few studies that have attempted to understand and utilize the contact modality of DEB drug delivery. Here, we developed a linear micro-patterned DEB (LMDEB) that applied higher contact pressure to enhance drug stamping to vascular tissue. Ex vivo and in vivo studies confirmed that higher contact pressure from micro-patterns increased the amount of drug delivered to the deeper regions of vessel. Finite element method simulation also showed significant increase of contact pressure between endothelium and micro-patterns. Quantitative analysis by high performance liquid chromatography indicated that LMDEBs delivered 2.3 times higher amount of drug to vascular tissue in vivo than conventional DEBs. Finally, efficacy studies using both atherosclerotic and ISR models demonstrated superior patency of diseased vessels treated with LMDEB compared to those treated with DEB.