bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy
Authors: Haikala Heidi M. , Anttila Johanna M. , Marques Elsa , Raatikainen Tiina , Ilander Mette , Hakanen Henna , Ala-Hongisto Hanna , Savelius Mariel , Balboa Diego , Von Eyss Bjoern , Eskelinen Vilja , Munne Pauliina , Nieminen Anni I. , Otonkoski Timo , Schüler Julia , Laajala Teemu D. , Aittokallio Tero , Sihto Harri , Mattson Johanna , Heikkilä Päivi , Leidenius Marjut , Joensuu Heikki , Mustjoki Satu , Kovanen Panu , Eilers Martin , Leverson Joel D. , Klefström Juha 
Published: February 2019

AbstractElevated MYC expression sensitizes tumor cells to apoptosis but the therapeutic potential of this mechanism remains unclear. We find, in a model of MYC-driven breast cancer, that pharmacological activation of AMPK strongly synergizes with BCL-2/BCL-XL inhibitors to activate apoptosis. We demonstrate the translational potential of an AMPK and BCL-2/BCL-XL co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer. Metformin combined with navitoclax or venetoclax efficiently inhibited tumor growth, conferred survival benefits and induced tumor infiltration by immune cells. However, withdrawal of the drugs allowed tumor re-growth with presentation of PD-1+/CD8+ T cell infiltrates, suggesting immune escape. A two-step treatment regimen, beginning with neoadjuvant metformin+venetoclax to induce apoptosis and followed by adjuvant metformin+venetoclax+anti-PD-1 treatment to overcome immune escape, led to durable antitumor responses even after drug withdrawal. We demonstrate that pharmacological reactivation of MYC-dependent apoptosis is a powerful antitumor strategy involving both tumor cell depletion and immunosurveillance.
Foiling covert channels and malicious classical post-processing units in quantum key distribution
Authors: Curty Marcos , Lo Hoi-Kwong 
Published: February 2019

AbstractThe existing paradigm for the security of quantum key distribution (QKD) suffers from two fundamental weaknesses. First, covert channels have emerged as an important threat and have attracted a lot of attention in security research in conventional information and communication systems. Covert channels (e.g. memory attacks) can fatally break the security of even device-independent quantum key distribution (DI-QKD), whenever QKD devices are re-used. Second, it is often implicitly assumed that the classical post-processing units of a QKD system are trusted. This is a rather strong assumption and is very hard to justify in practice. Here, we propose a new paradigm for the security of QKD that addresses these two fundamental problems. Specifically, we show that by using verifiable secret sharing and multiple optical devices and classical post-processing units, one could re-establish the security of QKD. Our techniques are rather general and they apply to both DI-QKD and non-DI-QKD.
Transcriptomic profiles of tumor-associated neutrophils reveal prominent roles in enhancing angiogenesis in liver tumorigenesis in zebrafish
Authors: Huo Xiaojing , Li Hankun , Li Zhen , Yan Chuan , Agrawal Ira , Mathavan Sinnakaruppan , Liu Jianjun , Gong Zhiyuan 
Published: February 2019

AbstractWe have previously demonstrated the pro-tumoral role of neutrophils using a kras-induced zebrafish hepatocarcinogenesis model. To further illustrate the molecular basis of the pro-tumoral role, Tumor-associated neutrophils (TANs) were isolated by fluorescence-activated cell sorting (FACS) and transcriptomic analyses were carried out by RNA-Seq. Differentially expressed gene profiles of TANs from larvae, male and female livers indicate great variations during liver tumorigenesis, but the common responsive canonical pathways included an immune pathway (Acute Phase Response Signaling), a liver metabolism-related pathway (LXR/RXR Activation) and Thrombin Signaling. Consistent with the pro-tumoral role of TANs, gene module analysis identified a consistent down-regulation of Cytotoxicity module, which may allow continued proliferation of malignant cells. Gene Set Enrichment Analysis indicated up-regulation of several genes promoting angiogenesis. Consistent with this, we found decreased density of blood vessels accompanied with decreased oncogenic liver sizes in neutrophil-depleted larvae. Collectively, our study has indicated some molecular mechanisms of the pro-tumoral roles of TANs in hepatocarcinogenesis, including weakened immune clearance against tumor cells and enhanced function in angiogenesis.
Dentate gyrus μ-opioid receptor-mediated neurogenic processes are associated with alterations in morphine self-administration
Authors: Zhang Haolin , Jia Meng , Wang Xue-Wei , Ye Can , Li Yijing , Wang Na , Elefant Felice , Ma Hui , Cui Cailian 
Published: February 2019

AbstractAdult hippocampal dentate gyrus (DG) neural stem cells (NSCs) continuously undergo proliferation and differentiation, producing new functional neurons that remodel existing synaptic circuits. Although proliferation of these adult DG NSCs has been implicated in opiate dependence, whether NSC neuronal differentiation and subsequent dendritogenesis are also involved in such addictive behavior remains unknown. Here, we ask whether opiate exposure alters differentiation and dendritogenesis of DG NSCs and investigate the possibility that these alterations contribute to opiate addiction. We show that rat morphine self-administration (MSA), a paradigm that effectively mimics human opiate addiction, increases NSC neuronal differentiation and promotes neuronal dendrite growth in the adult DG. Further, we demonstrate that the μ-opioid receptor (MOR) is expressed on DG NSCs and that MSA leads to a two-fold elevation of endogenous MOR levels in doublecortin expressing (DCX+) NSC progenies in the rat DG. MOR expression is also detected in the cultured rat NSCs and morphine treatment in vitro increases NSC neuronal differentiation and dendritogenesis, suggesting that MOR mediates the effect of morphine on NSC neuronal differentiation and maturation. Finally, we show that conditional overexpression of MOR in DG NSCs under a doxycycline inducible system leads to facilitation of the acquisition of MSA in rats, without affecting the extinction process. We advocate that targeting MOR selectively in the DG NSC population might offer a novel therapeutic intervention for morphine addiction.
A simple protocol for isolating mouse lung endothelial cells
Authors: Wang Jinping , Niu Niu , Xu Suowen , Jin Zheng Gen 
Published: February 2019

AbstractEndothelial dysfunction is the common molecular basis of multiple human diseases, such as atherosclerosis, diabetes, hypertension, and acute lung injury. Therefore, primary isolation of high-purity endothelial cells (ECs) is crucial to study the mechanisms of endothelial function and disease pathogenesis. Mouse lung ECs (MLECs) are widely used in vascular biology and lung cell biology studies such as pulmonary inflammation, angiogenesis, vessel permeability, leukocyte/EC interaction, nitric oxide production, and mechanotransduction. Thus, in this paper, we describe a simple, and reproducible protocol for the isolation and culture of MLECs from adult mice using collagenase I-based enzymatic digestion, followed by sequential sorting with PECAM1 (also known as CD31)- and ICAM2 (also known as CD102)-coated microbeads. The morphology of isolated MLECs were observed with phase contrast microscope. MLECs were authenticated by CD31 immunoblotting, and immunofluorescent staining of established EC markers VE-cadherin and von Willebrand factor (vWF). Cultured MLECs also showed functional characteristics of ECs, evidenced by DiI-oxLDL uptake assay and THP-1 monocyte adhesion assay. Finally, we used MLECs from endothelium-specific enhancer of zeste homolog 2 (EZH2) knockout mice to show the general applicability of our protocol. To conclude, we describe here a simple and reproducible protocol to isolate highly pure and functional ECs from adult mouse lungs. Isolation of ECs from genetically engineered mice is important for downstream phenotypic, genetic, or proteomic studies.
Repeated human deciduous tooth-derived dental pulp cell reprogramming factor transfection yields multipotent intermediate cells with enhanced iPS cell formation capability
Authors: Soda Miki , Saitoh Issei , Murakami Tomoya , Inada Emi , Iwase Yoko , Noguchi Hirofumi , Shibasaki Shinji , Kurosawa Mie , Sawami Tadashi , Terunuma Miho , Kubota Naoko , Terao Yutaka , Ohshima Hayato , Hayasaki Haruaki , Sato Masahiro 
Published: February 2019

AbstractHuman tissue-specific stem cells (hTSCs), found throughout the body, can differentiate into several lineages under appropriate conditions in vitro and in vivo. By transfecting terminally differentiated cells with reprogramming factors, we previously produced induced TSCs from the pancreas and hepatocytes that exhibit additional properties than iPSCs, as exemplified by very low tumour formation after xenogenic transplantation. We hypothesised that hTSCs, being partially reprogrammed in a state just prior to iPSC transition, could be isolated from any terminally differentiated cell type through transient reprogramming factor overexpression. Cytochemical staining of human deciduous tooth-derived dental pulp cells (HDDPCs) and human skin-derived fibroblasts following transfection with Yamanaka’s factors demonstrated increased ALP activity, a stem cell marker, three weeks after transfection albeit in a small percentage of clones. Repeated transfections (≤3) led to more efficient iPSC generation, with HDDPCs exhibiting greater multipotentiality at two weeks post-transfection than the parental intact HDDPCs. These results indicated the utility of iPSC technology to isolate TSCs from HDDPCs and fibroblasts. Generally, a step-wise loss of pluripotential phenotypes in ESCs/iPSCs occurs during their differentiation process. Our present findings suggest that the reverse phenomenon can also occur upon repeated introduction of reprogramming factors into differentiated cells such as HDDPCs and fibroblasts.
Diagnostic Efficacy of Synthesized 2D Digital Breast Tomosynthesis in Multi-ethnic Malaysian Population
Authors: Mumin N. Ab , Rahmat K. , Fadzli F. , Ramli M. T , Westerhout C. J. , Ramli N. , Rozalli F. I. , Ng K. H. 
Published: February 2019

AbstractSynthesized 2D images can be reconstructed from tomosynthesis images in breast imaging. This study aims to investigate the diagnostic efficacy of synthesized 2D images (C-View) in comparison to full field digital mammography (FFDM) when used with digital breast tomosynthesis (DBT) in multi-ethnic Malaysian population. FFDM and C-View images (n = 380) were independently evaluated by three readers through Breast Imaging Reporting and Data System (BI-RADS) categorisation, breast density and lesion characterisation. Statistical analysis was done comparing sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of C-View + DBT with FFDM + DBT as standard of reference. Very good interreader agreement in BI-RADS category and density assessment between C-View + DBT and FFDM + DBT, with high sensitivity, specificity, PPV and NPV of C-View + DBT when compared with FFDM + DBT. There was comparable PPV between C-View + DBT and FFDM + DBT, with histopathology as gold standard. High level of interreader agreement in BI-RADS category and density assessment for FFDM + DBT and C-View + DBT. There was good agreement between FFDM + DBT and C-View + DBT in mass characterization, and almost perfect agreement in calcification and asymmetric density. 52.2% lower radiation dose incurred when using C-View + DBT. Hence, synthesized 2D images are comparable to FFDM with reduction in radiation dose within the limits of Malaysian multi-ethnic population.
Electrical Heating Performance of Electro-Conductive Para-aramid Knit Manufactured by Dip-Coating in a Graphene/Waterborne Polyurethane Composite
Authors: Kim Hyelim , Lee Sunhee , Kim Hanseong 
Published: February 2019

AbstractAn electro-conductive para-aramid knit was manufactured by a dip-coating in a graphene/waterborne polyurethane(WPU) composite for confirming to use as a fabric heating element applicable to a protective clothing requiring durability. The para-aramid knit was dipped in 8 wt% graphene/WPU composite solution up to five-coat cycles. As a result of electro-conductive textile by number of dip-coating cycles, the electrical, and specifically electrical heating performances were increased number of cycles from one to five. The sample with the best electrical and electrical heating performance was the five-coat sample, and to improve those properties it was hot-pressed at 100 °C, 120 °C, 140 °C and 160 °C. After hot pressing, the entire surface of the sample was filled with graphene/WPU composite and indicated smoothly surface, thus the electrical and electrical heating performance was improved than the five-coat sample. The best performance of was indicated hot-pressed at 140 °C, with a surface resistivity and capacitance of 7.5 × 104 Ω/sq and 89.4 pF, respectively. When a voltage of 50 V was applied, the surface temperature reached 54.8 °C. The five-coat sample with hot-pressed at 140 °C could be applied to a heat-resistant para-aramid knit glove with the touch screen of a mobile phone and electric heating performance.
Tropical storms influence the movement behavior of a demersal oceanic fish species
Authors: Bacheler Nathan M. , Shertzer Kyle W. , Cheshire Robin T. , MacMahan Jamie H. 
Published: February 2019

AbstractExtreme weather events strongly influence marine, freshwater, and estuarine ecosystems in myriad ways. We quantified movements of a demersal oceanic fish species (gray triggerfish Balistes capriscus; N = 30) before, during, and after two hurricanes in 2017 using fine-scale acoustic telemetry at a 37-m deep study site in North Carolina, USA. During storms, gray triggerfish movement and emigration rates were 100% and 2550% higher, respectively, than on days with no storms. We found that increased movement rates were much more strongly correlated with wave orbital velocity (i.e., wave-generated oscillatory flow at the seabed) than either barometric pressure or bottom water temperature, two covariates that have been demonstrated to be important for organisms in shallower water. Higher movement rates during storms were due to increased mobility at night, and emigrations typically occurred at night in the direction of deeper water. Overall, we found significant storm effects on the movement behavior of a demersal fish species in the open ocean, despite our study occurring in deeper water than previous studies that have examined storm effects on animal movement. We conclude that tropical storms are a driving force behind the structure of marine ecosystems, in part by influencing movements of mobile animals.
Phage therapy against Pseudomonas aeruginosa infections in a cystic fibrosis zebrafish model
Authors: Cafora Marco , Deflorian Gianluca , Forti Francesca , Ferrari Laura , Binelli Giorgio , Briani Federica , Ghisotti Daniela , Pistocchi Anna 
Published: February 2019

AbstractCystic fibrosis (CF) is a hereditary disease due to mutations in the CFTR gene and causes mortality in humans mainly due to respiratory infections caused by Pseudomonas aeruginosa. In a previous work we used phage therapy, which is a treatment with a mix of phages, to actively counteract acute P. aeruginosa infections in mice and Galleria mellonella larvae. In this work we apply phage therapy to the treatment of P. aeruginosa PAO1 infections in a CF zebrafish model. The structure of the CFTR channel is evolutionary conserved between fish and mammals and cftr-loss-of-function zebrafish embryos show a phenotype that recapitulates the human disease, in particular with destruction of the pancreas. We show that phage therapy is able to decrease lethality, bacterial burden, and the pro-inflammatory response caused by PAO1 infection. In addition, phage administration relieves the constitutive inflammatory state of CF embryos. To our knowledge, this is the first time that phage therapy is used to cure P. aeruginosa infections in a CF animal model. We also find that the curative effect against PAO1 infections is improved by combining phages and antibiotic treatments, opening a useful therapeutic approach that could reduce antibiotic doses and time of administration.
Structure of two purple pigments, catechinopyranocyanidins A and B from the seed-coat of the small red bean, Vigna angularis
Authors: Yoshida Kumi , Nagai Nobukazu , Ichikawa Yoshiki , Goto Miki , Kazuma Kohei , Oyama Kin-ichi , Koga Kazushi , Hashimoto Masaru , Iuchi Satoru , Takaya Yoshiaki , Kondo Tadao 
Published: February 2019

AbstractThe small red bean, Vigna angularis, is primarily used to produce the “an-paste” component of Japanese sweets. Through the manufacturing process, the red seed-coat pigment is transferred to the colorless “an-particles”, imparting a purple color. However, the major pigment in the seed coat has not yet been identified, although it is historically presumed to be an anthocyanin. Here, we report the isolation and structural determination of two hydrophobic purple pigments in the seed coat via instrumental analysis and derivatization. The new pigments, catechinopyranocyanidins A and B, contain a novel pyranoanthocyanidin skeleton condensed with a catechin and cyanidin ring system, and no sugar moieties. Catechinopyranocyanidins A and B are diastereomers with a different configuration at the catechin moiety, and both are purple in color in strongly acidic-to-neutral media. Catechinopyranocyanidins A and B are very stable under dark conditions, but, labile to light and decompose to colorless compounds. Thus, these pigments exhibit quite different chemical properties compared to simple anthocyanidins.
Elevated carbon flux in deep waters of the South China Sea
Authors: Shih Yung-Yen , Lin Hsi-Hsiang , Li Dewang , Hsieh Hsueh-Han , Hung Chin-Chang , Chen Chen-Tung Arthur 
Published: February 2019

AbstractWe measured particulate organic carbon (POC) fluxes from the euphotic zone into the twilight zone and deep waters (>1000 m) that occurred between the shelf and the basin in the South China Sea (SCS) and at the SouthEast Asia Time Series Station (SEATS) using floating sediment trap arrays. Additionally, selected sinking particles were imaged by scanning electron microscope (SEM) to reveal particle morphology and composition. Results showed large variations in POC fluxes with elevated values (32–104 mg-C m−2 d−1) below the euphotic zone and a trend towards lower values in the deep SCS. Vertical POC fluxes measured in deep waters between the shelf and the SCS basin were much higher than those estimated by Martin’s attenuation equation. These elevated POC fluxes in deep waters were attributed to lateral particle transport as opposed to enhanced settling out of the euphotic zone. SEM images of sinking particles at 150 m show abundant marine biogenic detritus, while those in deep waters contained a higher proportion of lithogenic material. A great deal of the spatial variability in POC fluxes across the twilight zone and deep waters of the SCS cannot be represented by current biogeochemical models.
Blood-based analysis of type-2 diabetes mellitus susceptibility genes identifies specific transcript variants with deregulated expression and association with disease risk
Authors: Christodoulou Maria-Ioanna , Avgeris Margaritis , Kokkinopoulou Ioanna , Maratou Eirini , Mitrou Panayota , Kontos Christos K. , Pappas Efthimios , Boutati Eleni , Scorilas Andreas , Fragoulis Emmanuel G. 
Published: February 2019

AbstractDespite significant progress by genome-wide association studies, the ability of genetic variants to conduce to the prediction or prognosis of type-2 diabetes (T2D) is weak. Expression analysis of the corresponding genes may suggest possible links between single-nucleotide polymorphisms and T2D phenotype and/or risk. Herein, we investigated the expression patterns of 24 T2D-susceptibility genes, and their individual transcript variants (tv), in peripheral blood of T2D patients and controls (CTs), applying RNA-seq and real-time qPCR methodologies, and explore possible associations with disease features. Our data revealed the deregulation of certain transcripts in T2D patients. Among them, the down-regulation of CAPN10 tv3 was confirmed as an independent predictor for T2D. In patients, increased expression of CDK5 tv2, CDKN2A tv3 or THADA tv5 correlated positively with serum insulin levels, of CDK5 tv1 positively with % HbA1c levels, while in controls, elevated levels of TSPAN8 were associated positively with the presence of T2D family history. Herein, a T2D-specific expression profile of specific transcripts of disease-susceptibility genes is for the first time described in human peripheral blood. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.
3D-Spatial encoding with permanent magnets for ultra-low field magnetic resonance imaging
Authors: Vogel Michael W. , Guridi Ruben Pellicer , Su Jiasheng , Vegh Viktor , Reutens David C. 
Published: February 2019

AbstractWe describe with a theoretical and numerical analysis the use of small permanent magnets moving along prescribed helical paths for 3D spatial encoding and imaging without sample adjustment in ultra-low field magnetic resonance imaging (ULF-MRI). With our developed method the optimal magnet path and orientation for a given encoding magnet number and instrument architecture can be determined. As a proof-of-concept, we studied simple helical magnet paths and lengths for one and two encoding magnets to evaluate the imaging efficiency for a mechanically operated ULF-MRI instrument with permanent magnets. We demonstrate that a single encoding magnet moving around the sample in a single revolution suffices for the generation of a 3D image by back projection.
Robust and efficient knock-in in embryonic stem cells and early-stage embryos of the common marmoset using the CRISPR-Cas9 system
Authors: Yoshimatsu Sho , Okahara Junko , Sone Takefumi , Takeda Yuta , Nakamura Mari , Sasaki Erika , Kishi Noriyuki , Shiozawa Seiji , Okano Hideyuki 
Published: February 2019

AbstractGenome editing technology greatly facilitates the genetic modification of various cells and animals. The common marmoset (Callithrix jacchus), a small non-human primate which exhibits high reproductive efficiency, is a widely used animal model in biomedical research. Developing genome editing techniques in the common marmoset will further enhance its utility. Here, we report the successful establishment of a knock-in (KI) method for marmoset embryonic stem cells (ESCs), which is based on the CRISPR-Cas9 system. The use of CRISPR-Cas9, mediated by homologous recombination (HR), enhanced the KI efficiency in marmoset ESCs. Furthermore, we succeeded in performing KI in early-stage marmoset embryos. In the course of the experiments, we found that HR in the marmoset ESCs is innately highly efficient. This suggested that the marmoset possesses a repair mechanism for DNA double-strand breaks. The current study will facilitate the generation of genetically modified marmosets and gene function analysis in the marmoset.