bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability
Authors: Hendriks Delilah F. G. , Fredriksson Puigvert Lisa , Messner Simon , Mortiz Wolfgang , Ingelman-Sundberg Magnus 
Published: October 2016

AbstractDrug-induced cholestasis (DIC) is poorly understood and its preclinical prediction is mainly limited to assessing the compound’s potential to inhibit the bile salt export pump (BSEP). Here, we evaluated two 3D spheroid models, one from primary human hepatocytes (PHH) and one from HepaRG cells, for the detection of compounds with cholestatic liability. By repeatedly co-exposing both models to a set of compounds with different mechanisms of hepatotoxicity and a non-toxic concentrated bile acid (BA) mixture for 8 days we observed a selective synergistic toxicity of compounds known to cause cholestatic or mixed cholestatic/hepatocellular toxicity and the BA mixture compared to exposure to the compounds alone, a phenomenon that was more pronounced after extending the exposure time to 14 days. In contrast, no such synergism was observed after both 8 and 14 days of exposure to the BA mixture for compounds that cause non-cholestatic hepatotoxicity. Mechanisms behind the toxicity of the cholestatic compound chlorpromazine were accurately detected in both spheroid models, including intracellular BA accumulation, inhibition of ABCB11 expression and disruption of the F-actin cytoskeleton. Furthermore, the observed synergistic toxicity of chlorpromazine and BA was associated with increased oxidative stress and modulation of death receptor signalling. Combined, our results demonstrate that the hepatic spheroid models presented here can be used to detect and study compounds with cholestatic liability.
Effects of patch contrast and arrangement on benefits of clonal integration in a rhizomatous clonal plant
Authors: Wang Yong-Jian , Shi Xue-Ping , Wu Xiao-Jing , Meng Xue-Feng , Wang Peng-Cheng , Zhou Zhi-Xiang , Luo Fang-Li , Yu Fei-Hai 
Published: October 2016

AbstractThe availabilities of light and soil water resources usually spatially co-vary in natural habitats, and the spatial pattern of such co-variation may affect the benefits of physiological integration between connected ramets of clonal plants. In a greenhouse experiment, we grew connected or disconnected ramet pairs [consisting of a proximal (relatively old) and a distal (relative young) ramet] of a rhizomatous herb Iris japonica in four heterogeneous environments differing in patch arrangement (reciprocal vs. parallel patchiness of light and soil water) and patch contrast (high vs. low contrast of light and water). Biomass of the proximal part, distal part and clonal fragment of I. japonica were all significantly greater in the intact than in the severed treatment, in the parallel than in the reciprocal patchiness treatment and in the high than in the low contrast treatment, but the effect of severing the connection between ramet pairs did not depend on patch arrangement or contrast. Severing the connection decreased number of ramets of the distal part and the clonal fragment in the parallel patchiness arrangement, but not in the reciprocal patchiness arrangement. Therefore, the spatial arrangement of resource patches can alter the effects of clonal integration on asexual reproduction in I. japonica.
mdRNA-Seq analysis of marine microbial communities from the northern Red Sea
Authors: Hou Shengwei , Pfreundt Ulrike , Miller Dan , Berman-Frank Ilana , Hess Wolfgang R. 
Published: October 2016

AbstractMetatranscriptomic differential RNA-Seq (mdRNA-Seq) identifies the suite of active transcriptional start sites at single-nucleotide resolution through enrichment of primary transcript 5′ ends. Here we analyzed the microbial community at 45 m depth at Station A in the northern Gulf of Aqaba, Red Sea, during 500 m deep mixing in February 2012 using mdRNA-Seq and a parallel classical RNA-Seq approach. We identified promoters active in situ for five different pico-planktonic genera (the SAR11 clade of Alphaproteobacteria, Synechococcus of Cyanobacteria, Euryarchaeota, Thaumarchaeota, and Micromonas as an example for picoeukaryotic algae), showing the applicability of this approach to highly diverse microbial communities. 16S rDNA quantification revealed that 24% of the analyzed community were group II marine Euryarchaeota in which we identified a highly abundant non-coding RNA, Tan1, and detected very high expression of genes encoding intrinsically disordered proteins, as well as enzymes for the synthesis of specific B vitamins, extracellular peptidases, carbohydrate-active enzymes, and transport systems. These results highlight previously unknown functions of Euryarchaeota with community-wide relevance. The complementation of metatranscriptomic studies with mdRNA-Seq provides substantial additional information regarding transcriptional start sites, promoter activities, and the identification of non-coding RNAs.
TGF-β induces p53/Smads complex formation in the PAI-1 promoter to activate transcription
Authors: Kawarada Yuki , Inoue Yasumichi , Kawasaki Fumihiro , Fukuura Keishi , Sato Koichi , Tanaka Takahito , Itoh Yuka , Hayashi Hidetoshi 
Published: October 2016

AbstractTransforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription. p53 forms a complex with Smad2/3 in the PAI-1 promoter to recruit histone acetyltransferase CREB-binding protein (CBP) and enhance histone H3 acetylation, resulting in transcriptional activation of the PAI-1 gene. Importantly, p53 is required for TGF-β-induced cytostasis and PAI-1 is involved in the cytostatic activity of TGF-β in several cell lines. Our results suggest that p53 enhances TGF-β-induced cytostatic effects by activating PAI-1 transcription, and the functional switching of TGF-β is partially caused by p53 mutation or p53 inactivation during cancer progression. It is expected that these findings will contribute to optimization of TGF-β-targeting therapies for cancer.
LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL)
Authors: Chen Gang , Yu Dongsheng , Nian Xue , Liu Junyi , Koenig Ronald J. , Xu Bin , Sheng Liang 
Published: October 2016

AbstractNonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding. Loss of SRA in primary hepatocytes or a hepatocyte cell line upregulates, but forced expression of SRA inhibits ATGL expression and free fatty acids (FFA) β-oxidation. SRA inhibits ATGL promoter activity, primarily by inhibiting the otherwise-inductive effects of the transcription factor, forkhead box protein O1 (FoxO1). Our data reveal a novel function of SRA in promoting hepatic steatosis through repression of ATGL expression.
Gas Protection of Two-Dimensional Nanomaterials from High-Energy Impacts
Authors: Xing Tan , Mateti Srikanth , Li Lu Hua , Ma Fengxian , Du Aijun , Gogotsi Yury , Chen Ying 
Published: October 2016

AbstractTwo-dimensional (2D) materials can be produced using ball milling with the help of liquid surfactants or solid exfoliation agents, as ball milling of bulk precursor materials usually produces nanosized particles because of high-energy impacts. Post-milling treatment is thus needed to purify the nanosheets. We show here that nanosheets of graphene, BN, and MoS2 can be produced by ball milling of their bulk crystals in the presence of ammonia or a hydrocarbon ethylene gas and the obtained nanosheets remain flat and maintain their single-crystalline structure with low defects density even after a long period of time; post-milling treatment is not needed. This study does not just demonstrate production of nanosheets using ball milling, but reveals surprising indestructible behaviour of 2D nanomaterials in ammonia or hydrocarbon gas under the high-energy impacts; in other milling atmospheres such as air, nitrogen or argon the same milling treatment produces nanosized particles. A systematic study reveals chemisorption of ammonia and hydrocarbon gases and chemical reactions occurring at defect sites, which heal the defects by saturating the dangling bonds. Density functional theory was used to understand the mechanism of mechanochemical reactions. Ball milling in ammonia or hydrocarbon is promising for mass-production of pure nanosheets.
Independent Long Fingers are not Essential for a Grasping Hand
Authors: Montagnani Federico , Controzzi Marco , Cipriani Christian 
Published: October 2016

AbstractThe human hand is a complex integrated system with motor and sensory components that provides individuals with high functionality and elegant behaviour. In direct connection with the brain, the hand is capable of performing countless actions ranging from fine digit manipulation to the handling of heavy objects. However the question of which movements mostly contribute to the manipulation skills of the hand, and thus should be included in prosthetic hands, is yet to be answered. Building from our previous work, and assuming that a hand with independent long fingers allowed performance comparable to a hand with coupled fingers, here we explored the actual contribution of independent fingers while performing activities of daily living using custom built orthoses. Our findings show that, when an opposable thumb is present, independent long fingers provide a measureable advantage in performing activities of daily living only when precision grasps are involved. In addition, the results suggest that the remarkable grasping skills of the human hand rely more on the independent abduction/adduction of the fingers than on their independent flexion/extension. These findings are of interest to the designers of artificial hands, including biomimetic prostheses and exoskeletons.
Choline and betaine consumption lowers cancer risk: a meta-analysis of epidemiologic studies
Authors: Sun Shanwen , Li Xiao , Ren Anjing , Du Mulong , Du Haina , Shu Yongqian , Zhu Lingjun , Wang Wei 
Published: October 2016

AbstractA number of human and animal in vitro or in vivo studies have investigated the relationship between dietary choline and betaine and cancer risk, suggesting that choline and betaine consumption may be protective for cancer. There are also a few epidemiologic studies exploring this relationship, however, with inconsistent conclusions. The PubMed and Embase were searched, from their inception to March 2016, to identify relevant studies and we brought 11 articles into this meta-analysis eventually. The pooled relative risks (RRs) of cancer for the highest versus the lowest range were 0.82 (95% CI, 0.70 to 0.97) for choline consumption only, 0.86 (95%CI, 0.76 to 0.97) for betaine consumption only and 0.60 (95%CI, 0.40 to 0.90) for choline plus betaine consumption, respectively. Significant protective effect of dietary choline and betaine for cancer was observed when stratified by study design, location, cancer type, publication year, sex and quality score of study. An increment of 100 mg/day of choline plus betaine intake helped reduce cancer incidence by 11% (0.89, 95% CI, 0.87 to 0.92) through a dose-response analysis. To conclude, choline and betaine consumption lowers cancer incidence in this meta-analysis, but further studies are warranted to verify the results.
Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia
Authors: Ohayon Delphine , De Chiara Alessia , Chapuis Nicolas , Candalh Céline , Mocek Julie , Ribeil Jean-Antoine , Haddaoui Lamya , Ifrah Norbert , Hermine Olivier , Bouillaud Frédéric , Frachet Philippe , Bouscary Didier , Witko-Sarsat Véronique 
Published: October 2016

AbstractCytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux.
Regional-specific effect of fluoxetine on rapidly dividing progenitors along the dorsoventral axis of the hippocampus
Authors: Zhou Qi-Gang , Lee Daehoon , Ro Eun Jeoung , Suh Hoonkyo 
Published: October 2016

AbstractHippocampus-dependent cognitive and emotional function appears to be regionally dissociated along the dorsoventral (DV) axis of the hippocampus. Recent observations that adult hippocampal neurogenesis plays a critical role in both cognition and emotion raised an interesting question whether adult neurogenesis within specific subregions of the hippocampus contributes to these distinct functions. We examined the regional-specific and cell type-specific effects of fluoxetine, which requires adult hippocampal neurogenesis to function as an antidepressant, on the proliferation of hippocampal neural stem cells (NSCs). Fluoxetine specifically increased proliferation of NSCs located in the ventral region of the hippocampus while the mitotic index of NSCs in the dorsal portion of the hippocampus remained unaltered. Moreover, within the ventral hippocampus, type II NSC and neuroblast populations specifically responded to fluoxetine, showing increased proliferation; however, proliferation of type I NSCs was unchanged in response to fluoxetine. Activation or inhibition of serotonin receptor 1A (5-HTR1A) recapitulated or abolished the effect of fluoxetine on proliferation of type II NSCs and neuroblast populations in the ventral hippocampus. Our study showed that the effect of fluoxetine on proliferation is dependent upon the type and the position of the NSCs along the DV axis of the hippocampus.
Factor XIII-A transglutaminase deficient mice show signs of metabolically healthy obesity on high fat diet
Authors: Myneni Vamsee D. , Mousa Aisha , Kaartinen Mari T. 
Published: October 2016

AbstractF13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1−/− mice. F13a1−/− and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks. Weight gain, total fat mass and fat pad mass, glucose handling, insulin sensitivity, energy expenditure and, morphological and biochemical analysis of adipose tissue was performed. We show that mice lacking FXIII-A gain weight on obesogenic diet, similarly as wild type mice, but exhibit a number of features of metabolically healthy obesity such as protection from developing diet-induced insulin resistance and hyperinsulinemia. Mice also show normal fasting glucose levels, larger adipocytes, decreased extracellular matrix accumulation and inflammation of adipose tissue, as well as decreased circulating triglycerides. This study reveals that FXIII-A transglutaminase can regulate whole body insulin sensitivity and may have a role in the development of diet-induced metabolic disturbances.
Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status
Authors: Cheng Yang , Lu Feng , Wang Bo , Li Jian , Han Jin-Hee , Ito Daisuke , Kong Deok-Hoon , Jiang Lubin , Wu Jian , Ha Kwon-Soo , Takashima Eizo , Sattabongkot Jetsumon , Cao Jun , Nyunt Myat Htut , Kyaw Myat Phone , Desai Sanjay A. , Miller Louis H. , Tsuboi Takafumi , Han Eun-Taek 
Published: October 2016

AbstractPlasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA), that bound human erythrocytes regardless of Duffy antigen status. PvGAMA was localized at the microneme in the mature schizont-stage parasites. The antibodies against PvGAMA fragments inhibited PvGAMA binding to erythrocytes in a dose-dependent manner. The erythrocyte-specific binding activities of PvGAMA were significantly reduced by chymotrypsin treatment. Thus, PvGAMA may be an adhesion molecule for the invasion of Duffy-positive and -negative human erythrocytes.
Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma
Authors: Sun Wu-Yi , Hu Shan-Shan , Wu Jing-Jing , Huang Qiong , Ma Yang , Wang Qing-Tong , Chen Jing-Yu , Wei Wei 
Published: October 2016

Abstractβ-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that β-arrestin2 level, but not β-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, β-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. β-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that β-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, β-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that β-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low β-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC.
Wall Teichoic Acids Are Involved in the Medium-Induced Loss of Function of the Autolysin CD11 against Clostridium difficile
Authors: Wu Xia , Paskaleva Elena E. , Mehta Krunal K. , Dordick Jonathan S. , Kane Ravi S. 
Published: October 2016

AbstractBacterial lysins are potent antibacterial enzymes with potential applications in the treatment of bacterial infections. Some lysins lose activity in the growth media of target bacteria, and the underlying mechanism remains unclear. Here we use CD11, an autolysin of Clostridium difficile, as a model lysin to demonstrate that the inability of this enzyme to kill C. difficile in growth medium is not associated with inhibition of the enzyme activity by medium, or the modification of the cell wall peptidoglycan. Rather, wall teichoic acids (WTAs) appear to prevent the enzyme from binding to the cells and cleaving the cell wall peptidoglycan. By partially blocking the biosynthetic pathway of WTAs with tunicamycin, cell binding improved and the lytic efficacy of CD11 was significantly enhanced. This is the first report of the mechanism of lysin inactivation in growth medium, and provides insights into understanding the behavior of lysins in complex environments, including the gastrointestinal tract.
Software-defined microwave photonic filter with high reconfigurable resolution
Authors: Wei Wei , Yi Lilin , Jaouën Yves , Hu Weisheng 
Published: October 2016

AbstractMicrowave photonic filters (MPFs) are of great interest in radio frequency systems since they provide prominent flexibility on microwave signal processing. Although filter reconfigurability and tunability have been demonstrated repeatedly, it is still difficult to control the filter shape with very high precision. Thus the MPF application is basically limited to signal selection. Here we present a polarization-insensitive single-passband arbitrary-shaped MPF with ~GHz bandwidth based on stimulated Brillouin scattering (SBS) in optical fibre. For the first time the filter shape, bandwidth and central frequency can all be precisely defined by software with ~MHz resolution. The unprecedented multi-dimensional filter flexibility offers new possibilities to process microwave signals directly in optical domain with high precision thus enhancing the MPF functionality. Nanosecond pulse shaping by implementing precisely defined filters is demonstrated to prove the filter superiority and practicability.