bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Cannabinoid Receptor 2 Blockade during Immunization Heightens Intensity and Breadth of Antigen-specific Antibody Responses in Young and Aged mice
Authors: Dotsey Emmanuel , Ushach Irina , Pone Egest , Nakajima Rie , Jasinskas Algis , Argueta Donovan A. , Dillon Andrea , DiPatrizio Nicholas , Davies Huw , Zlotnik Albert , Crompton Peter D. , Felgner Philip L. 
Published: February 2017

AbstractThe hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation. We have also established that 2-AG levels are upregulated in the serum and in the lymph node of mice during vaccination. We hypothesized that the intrinsic release of eCBs from immune cells during activation by pathogenic antigens mitigate inflammation, but also suppress overall innate and adaptive immune response. Here we demonstrate, for the first time, that transient administration of the cannabinoid receptor 2 antagonist AM630 (10 mg/kg) or inverse agonist JTE907 (3 mg/kg) during immunization heightens the intensity and breadth of antigen-specific immune responses in young and aged mice through the upregulation of immunomodulatory genes in secondary lymphoid tissues.
Molecular Basis of ABHD5 Lipolysis Activation
Authors: Sanders Matthew A. , Zhang Huamei , Mladenovic Ljiljana , Tseng Yan Yuan , Granneman James G. 
Published: February 2017

AbstractAlpha-beta hydrolase domain-containing 5 (ABHD5), the defective gene in human Chanarin-Dorfman syndrome, is a highly conserved regulator of adipose triglyceride lipase (ATGL)-mediated lipolysis that plays important roles in metabolism, tumor progression, viral replication, and skin barrier formation. The structural determinants of ABHD5 lipolysis activation, however, are unknown. We performed comparative evolutionary analysis and structural modeling of ABHD5 and ABHD4, a functionally distinct paralog that diverged from ABHD5 ~500 million years ago, to identify determinants of ABHD5 lipolysis activation. Two highly conserved ABHD5 amino acids (R299 and G328) enabled ABHD4 (ABHD4 N303R/S332G) to activate ATGL in Cos7 cells, brown adipocytes, and artificial lipid droplets. The corresponding ABHD5 mutations (ABHD5 R299N and ABHD5 G328S) selectively disrupted lipolysis without affecting ATGL lipid droplet translocation or ABHD5 interactions with perilipin proteins and ABHD5 ligands, demonstrating that ABHD5 lipase activation could be dissociated from its other functions. Structural modeling placed ABHD5 R299/G328 and R303/G332 from gain-of-function ABHD4 in close proximity on the ABHD protein surface, indicating they form part of a novel functional surface required for lipase activation. These data demonstrate distinct ABHD5 functional properties and provide new insights into the functional evolution of ABHD family members and the structural basis of lipase regulation.
Epigenetic and genetic dissections of UV-induced global gene dysregulation in skin cells through multi-omics analyses
Authors: Shen Yao , Stanislauskas Milda , Li Gen , Zheng Deyou , Liu Liang 
Published: February 2017

AbstractTo elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis. Integration of the multi-omics data revealed that UVR-induced transcriptional dysregulation of a subset of genes was attributable to either genetic mutations or global redistribution of H3K27ac. H3K27ac redistribution further led to the formation of distinctive super enhancers in UV-irradiated cells. Our analysis also identified several new UV target genes, including CYP24A1, GJA5, SLAMF7 and ETV1, which were frequently dysregulated in human squamous cell carcinomas, highlighting their potential as new molecular targets for prevention or treatment of UVR-induced skin cancers. Taken together, our concurrent multi-omics analyses provide new mechanistic insights into the complex molecular networks underlying UV photobiological effects, which have important implications in understanding its impact on skin homeostasis and pathogenesis.
RNA-Seq-based transcriptomic and metabolomic analysis reveal stress responses and programmed cell death induced by acetic acid in Saccharomyces cerevisiae
Authors: Dong Yachen , Hu Jingjin , Fan Linlin , Chen Qihe 
Published: February 2017

AbstractAs a typical harmful inhibitor in cellulosic hydrolyzates, acetic acid not only hinders bioethanol production, but also induces cell death in Saccharomyces cerevisiae. Herein, we conducted both transcriptomic and metabolomic analyses to investigate the global responses under acetic acid stress at different stages. There were 295 up-regulated and 427 down-regulated genes identified at more than two time points during acetic acid treatment (150 mM, pH 3.0). These differentially expressed genes (DEGs) were mainly involved in intracellular homeostasis, central metabolic pathway, transcription regulation, protein folding and stabilization, ubiquitin-dependent protein catabolic process, vesicle-mediated transport, protein synthesis, MAPK signaling pathways, cell cycle, programmed cell death, etc. The interaction network of all identified DEGs was constructed to speculate the potential regulatory genes and dominant pathways in response to acetic acid. The transcriptional changes were confirmed by metabolic profiles and phenotypic analysis. Acetic acid resulted in severe acidification in both cytosol and mitochondria, which was different from the effect of extracellular pH. Additionally, the imbalance of intracellular acetylation was shown to aggravate cell death under this stress. Overall, this work provides a novel and comprehensive understanding of stress responses and programmed cell death induced by acetic acid in yeast.
Possible Involvement of F1F0-ATP synthase and Intracellular ATP in Keratinocyte Differentiation in normal skin and skin lesions
Authors: Xiaoyun Xie , Chaofei Han , Weiqi Zeng , Chen Chen , Lixia Lu , Queping Liu , Cong Peng , Shuang Zhao , Juan Su , Xiang Chen 
Published: February 2017

AbstractThe F1F0-ATP synthase, an enzyme complex, is mainly located on the mitochondrial inner membrane or sometimes cytomembrane to generate or hydrolyze ATP, play a role in cell proliferation. This study focused on the role of F1F0-ATP synthase in keratinocyte differentiation, and its relationship with intracellular and extracellular ATP (InATP and ExATP). The F1F0-ATP synthase β subunit (ATP5B) expression in various skin tissues and confluence-dependent HaCaT differentiation models was detected. ATP5B expression increased with keratinocyte and HaCaT cell differentiation in normal skin, some epidermis hyper-proliferative diseases, squamous cell carcinoma, and the HaCaT cell differentiation model. The impact of InATP and ExATP content on HaCaT differentiation was reflected by the expression of the differentiation marker involucrin. Inhibition of F1F0-ATP synthase blocked HaCaT cell differentiation, which was associated with a decrease of InATP content, but not with changes of ExATP. Our results revealed that F1F0-ATP synthase expression is associated with the process of keratinocyte differentiation which may possibly be related to InATP synthesis.
Development and evaluation of a risk score for type 2 diabetes mellitus among middle-aged Chinese rural population based on the RuralDiab Study
Authors: Zhou Hao , Li Yuqian , Liu Xiaotian , Xu Fei , Li Linlin , Yang Kaili , Qian Xinling , Liu Ruihua , Bie Ronghai , Wang Chongjian 
Published: February 2017

AbstractThe purpose of this study was to establish a simple and effective risk score for type 2 diabetes mellitus (T2DM) in middle-aged rural Chinese. Total of 5453 participants aged 30–59 years from the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study were recruited for establishing the RuralDiab risk score by using logistic regression analysis. The RuralDiab risk score was validated in a prospective study from Henan Province of China, and compared with previous risk scores by using the receiver-operating characteristics cure. Ultimately, sex, age, family history of diabetes, physical activity, waist circumference, history of dyslipidemia, diastolic blood pressure, body mass index were included in the RuralDiab risk score (range from 0 to 36), and the optimal cutoff value was 17 with 67.9% sensitivity and 67.8% specificity. The area under the cures (AUC) of the RuralDiab risk score was 0.723(95%CI: 0.710–0.735) for T2DM in validation population, which was significant higher than the American Diabetes Association score (AUC: 0.636), the Inter99 score (AUC: 0.669), the Oman risk score (AUC: 0.675). The RuralDiab risk score was established and demonstrated an appropriate performance for predicting T2DM in middle-aged Chinese rural population. Further studies for validation should be implemented in different populations.
Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity
Authors: Oeck S. , Al-Refae K. , Riffkin H. , Wiel G. , Handrick R. , Klein D. , Iliakis G. , Jendrossek V. 
Published: February 2017

AbstractThe survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with prominent nuclear access, the phospho-mimicking Akt1-TDSD and the clinically relevant PH-domain mutation Akt1-E17K, accelerated DSB repair and improved survival of irradiated Tramp-C1 murine prostate cancer cells and Akt1-knockout murine embryonic fibroblasts in vitro, the classical constitutively active membrane-targeted myrAkt1 mutant had the opposite effects. Interestingly, DNA-PKcs directly phosphorylated Akt1 at S473 in an in vitro kinase assay but not vice-versa. Pharmacological inhibition of DNA-PKcs or Akt restored radiosensitivity in tumour cells expressing Akt1-E17K or Akt1-TDSD. In conclusion, Akt1-mediated radioresistance depends on its activation state and nuclear localization and is accessible to pharmacologic inhibition.
Fibulin-6 regulates pro-fibrotic TGF-β responses in neonatal mouse ventricular cardiac fibroblasts
Authors: Chowdhury Arpita , Hasselbach Lisa , Echtermeyer Frank , Jyotsana Nidhi , Theilmeier Gregor , Herzog Christine 
Published: February 2017

AbstractFibulin-6, an essential component of extracellular matrix determines the architecture of cellular junctions in tissues undergoing strain. Increased expression and deposition of fibulin-6 facilitates fibroblast migration in response to TGF-β, following myocardial infarction in mouse heart. The underlying mechanism still remains elusive. In conjunction with our previous study, we have now demonstrated that in fibulin-6 knockdown (KD) fibroblasts, not only TGF-β dependent migration, but also stress fiber formation, cellular networking and subsequently fibroblast wound contraction is almost abrogated. SMAD dependent TGF-β pathway shows ~75% decreased translocation of R-SMAD and co-SMAD into the nucleus upon fibulin-6 KD. Consequently, SMAD dependent pro-fibrotic gene expression is considerably down regulated to basal levels both in mRNA and protein. Also, investigating the non-SMAD pathways we observed a constitutive increase in pERK-levels in fibulin-6 KD fibroblast compared to control, but no change was seen in pAKT. Immunoprecipitation studies revealed 60% reduced interaction of TGF-β receptor II and I (TGFRII and I) accompanied by diminished phosphorylation of TGFRI at serin165 in fibulin-6 KD cells. In conclusion, fibulin-6 plays an important role in regulating TGF-β mediated responses, by modulating TGF-β receptor dimerization and activation to further trigger downstream pathways.
Room temperature texturing of austenite/ferrite steel by electropulsing
Authors: Rahnama Alireza , Qin Rongshan 
Published: February 2017

AbstractThe work reports an experimental observation on crystal rotation in a duplex (austenite + ferrite) steel induced by the electropulsing treatment at ambient temperature, while the temperature rising due to ohmic heating in the treatment was negligible. The results demonstrate that electric current pulses are able to dissolve the initial material’s texture that has been formed in prior thermomechanical processing and to produce an alternative texture. The results were explained in terms of the instability of an interface under perturbation during pulsed electromigation.
High-velocity deformation of Al0.3CoCrFeNi high-entropy alloy: Remarkable resistance to shear failure
Authors: Li Z. , Zhao S. , Diao H. , Liaw P. K. , Meyers M. A. 
Published: February 2017

AbstractThe mechanical behavior of a single phase (fcc) Al0.3CoCrFeNi high-entropy alloy (HEA) was studied in the low and high strain-rate regimes. The combination of multiple strengthening mechanisms such as solid solution hardening, forest dislocation hardening, as well as mechanical twinning leads to a high work hardening rate, which is significantly larger than that for Al and is retained in the dynamic regime. The resistance to shear localization was studied by dynamically-loading hat-shaped specimens to induce forced shear localization. However, no adiabatic shear band could be observed. It is therefore proposed that the excellent strain hardening ability gives rise to remarkable resistance to shear localization, which makes this material an excellent candidate for penetration protection applications such as armors.
Identification of the core regulators of the HLA I-peptide binding process
Authors: Zhang Yu-Hang , Xing Zhihao , Liu Chenglin , Wang ShaoPeng , Huang Tao , Cai Yu-Dong , Kong Xiangyin 
Published: February 2017

AbstractDuring the display of peptide/human leukocyte antigen (HLA) -I complex for further immune recognition, the cleaved and transported antigenic peptides have to bind to HLA-I protein and the binding affinity between peptide epitopes and HLA proteins directly influences the immune recognition ability in human beings. Key factors affecting the binding affinity during the generation, selection and presentation processes of HLA-I complex have not yet been fully discovered. In this study, a new method describing the HLA class I-peptide interactions was proposed. Three hundred and forty features of HLA I proteins and peptide sequences were utilized for analysis by four candidate algorithms, screening the optimal classifier. Features derived from the optimal classifier were further selected and systematically analyzed, revealing the core regulators. The results validated the hypothesis that features of HLA I proteins and related peptides simultaneously affect the binding process, though with discrepant redundancy. Besides, the high relative ratio (16/20) of the amino acid composition features suggests the unique role of sequence signatures for the binding processes. Integrating biological, evolutionary and chemical features of both HLA I molecules and peptides, this study may provide a new perspective of the underlying mechanisms of HLA I-mediated immune reactions.
Hepatocyte-secreted extracellular vesicles modify blood metabolome and endothelial function by an arginase-dependent mechanism
Authors: Royo Felix , Moreno Laura , Mleczko Justyna , Palomo Laura , Gonzalez Esperanza , Cabrera Diana , Cogolludo Angel , Vizcaino Francisco Perez , van-Liempd Sebastiaan , Falcon-Perez Juan M. 
Published: February 2017

AbstractHepatocytes release extracellular vesicles (EVs) loaded with signaling molecules and enzymes into the bloodstream. Although the importance of EVs in the intercellular communication is already recognized, the metabolic impact of the enzymes carried by these vesicles is still unclear. We evaluated the global effect of the enzymatic activities of EVs by performing untargeted metabolomic profiling of serum samples after their exposure to EVs. This approach revealed a significant change in the abundance of 94 serum metabolic signals. Our study shows that these vesicles modify the concentration of metabolites of different chemical nature including metabolites related to arginine metabolism, which regulates vascular function. To assess the functional relevance of this finding, we examined the levels of arginase-1 protein and its activity in the hepatic EVs carrying the exosomal markers CD81 and CD63. Remarkably, the arginase activity was also detected in EVs isolated from the serum in vivo, and this vesicular activity significantly increased under liver-damaging conditions. Finally, we demonstrated that EVs secreted by hepatocytes inhibited the acetylcholine-induced relaxation in isolated pulmonary arteries, via an arginase-dependent mechanism. In summary, our study demonstrates that the hepatocyte-released EVs are metabolically active, affecting a number of serum metabolites involved in oxidative stress metabolism and the endothelial function.
Zebrafish tracking using convolutional neural networks
Authors: XU Zhiping , Cheng Xi En 
Published: February 2017

AbstractKeeping identity for a long term after occlusion is still an open problem in the video tracking of zebrafish-like model animals, and accurate animal trajectories are the foundation of behaviour analysis. We utilize the highly accurate object recognition capability of a convolutional neural network (CNN) to distinguish fish of the same congener, even though these animals are indistinguishable to the human eye. We used data augmentation and an iterative CNN training method to optimize the accuracy for our classification task, achieving surprisingly accurate trajectories of zebrafish of different size and age zebrafish groups over different time spans. This work will make further behaviour analysis more reliable.
Interference between variants of peach latent mosaic viroid reveals novel features of its fitness landscape: implications for detection
Authors: Serra Pedro , Bertolini Edson , Martínez M. Carmen , Cambra Mariano , Flores Ricardo 
Published: February 2017

AbstractNatural populations of peach latent mosaic viroid (PLMVd) are complex mixtures of variants. During routine testing, TaqMan rtRT-PCR and RNA gel-blot hybridization produced discordant results with some PLMVd isolates. Analysis of the corresponding populations showed that they were exclusively composed of variants (of class II) with a structural domain different from that of the reference and many other variants (of class I) targeted by the TaqMan rtRT-PCR probe. Bioassays in peach revealed that a representative PLMVd variant of class II replicated without symptoms, generated a progeny with low nucleotide diversity, and, intriguingly, outcompeted a representative symptomatic variant of class I when co-inoculated in equimolecular amounts. A number of informative positions associated with the higher fitness of variants of class II have been identified, and novel sets of primers and probes for universal or specific TaqMan rtRT-PCR detection of PLMVd variants have been designed and tested.
In vitro differentiation of fertile sperm from cryopreserved spermatogonia of the endangered endemic cyprinid honmoroko (Gnathopogon caerulescens)
Authors: Higaki Shogo , Shimada Manami , Kawamoto Kazuaki , Todo Takaaki , Kawasaki Toshihiro , Tooyama Ikuo , Fujioka Yasuhiro , Sakai Noriyoshi , Takada Tatsuyuki 
Published: February 2017

AbstractMany endemic fish species are threatened with extinction. Conservation strategies and the restoration of endemic fish after extinction must therefore be investigated. Although sperm cryopreservation is indispensable for the conservation of endangered fishes, the limited number of mature fish and limited availability (volume and period) of sperm from small endemic fish hinders the optimization and practical use of this material. In this report, we demonstrate the in vitro differentiation of fertile sperm from cryopreserved spermatogonia of juveniles of the endangered small cyprinid honmoroko (Gnathopogon caerulescens), which is endemic to Lake Biwa in Japan. The entire process of spermatogenesis was recapitulated in vitro using cryopreserved spermatogonia of non-spawning adult and juvenile fish. The differentiation of sperm from spermatogonia was captured as a time-lapse video and confirmed by 5-ethynyl-2′-deoxyuridine (EdU) incorporation into sperm. Fertility was demonstrated by artificial insemination. These results suggest that the combination of cryopreservation of spermatogonia and in vitro sperm differentiation will provide a new and promising strategy for the preservation of paternal genetic materials.
Broadband gradient impedance matching using an acoustic metamaterial for ultrasonic transducers
Authors: Li Zheng , Yang Dan-Qing , Liu Shi-Lei , Yu Si-Yuan , Lu Ming-Hui , Zhu Jie , Zhang Shan-Tao , Zhu Ming-Wei , Guo Xia-Sheng , Wu Hao-Dong , Wang Xin-Long , Chen Yan-Feng 
Published: February 2017

AbstractHigh-quality broadband ultrasound transducers yield superior imaging performance in biomedical ultrasonography. However, proper design to perfectly bridge the energy between the active piezoelectric material and the target medium over the operating spectrum is still lacking. Here, we demonstrate a new anisotropic cone-structured acoustic metamaterial matching layer that acts as an inhomogeneous material with gradient acoustic impedance along the ultrasound propagation direction. When sandwiched between the piezoelectric material unit and the target medium, the acoustic metamaterial matching layer provides a broadband window to support extraordinary transmission of ultrasound over a wide frequency range. We fabricated the matching layer by etching the peeled silica optical fibre bundles with hydrofluoric acid solution. The experimental measurement of an ultrasound transducer equipped with this acoustic metamaterial matching layer shows that the corresponding −6 dB bandwidth is able to reach over 100%. This new material fully enables new high-end piezoelectric materials in the construction of high-performance ultrasound transducers and probes, leading to considerably improved resolutions in biomedical ultrasonography and compact harmonic imaging systems.