bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death
Authors: Hartmann Boris M. , Albrecht Randy A. , Zaslavsky Elena , Nudelman German , Pincas Hanna , Marjanovic Nada , Schotsaert Michael , Martínez-Romero Carles , Fenutria Rafael , Ingram Justin P. , Ramos Irene , Fernandez-Sesma Ana , Balachandran Siddharth , García-Sastre Adolfo , Sealfon Stuart C. 
Published: November 2017

AbstractThe risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host–pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death. Only DC infected with seasonal IAV, but not with pandemic IAV, enhance maturation of uninfected DC and T cell proliferation. In vivo, circulating T cell levels are reduced after pandemic, but not seasonal, IAV infection. Using recombinant viruses, we identify the HA genomic segment as the mediator of cell death inhibition. These results show how pandemic influenza viruses subvert the immune response.
Bacteriophage T5 tail tube structure suggests a trigger mechanism for Siphoviridae DNA ejection
Authors: Arnaud Charles-Adrien , Effantin Grégory , Vivès Corinne , Engilberge Sylvain , Bacia Maria , Boulanger Pascale , Girard Eric , Schoehn Guy , Breyton Cécile 
Published: November 2017

AbstractThe vast majority of phages, bacterial viruses, possess a tail ensuring host recognition, cell wall perforation and safe viral DNA transfer from the capsid to the host cytoplasm. Long flexible tails are formed from the tail tube protein (TTP) polymerised as hexameric rings around and stacked along the tape measure protein (TMP). Here, we report the crystal structure of T5 TTP pb6 at 2.2 Å resolution. Pb6 is unusual in forming a trimeric ring, although structure analysis reveals homology with all classical TTPs and related tube proteins of bacterial puncturing devices (type VI secretion system and R-pyocin). Structures of T5 tail tubes before and after interaction with the host receptor were determined by cryo-electron microscopy at 6 Å resolution. Comparison of these two structures reveals that host-binding information is not propagated to the capsid through conformational changes in the tail tube, suggesting a role of the TMP in this information transduction process.
A two-dimensional Fe-doped SnS2 magnetic semiconductor
Authors: Li Bo , Xing Tao , Zhong Mianzeng , Huang Le , Lei Na , Zhang Jun , Li Jingbo , Wei Zhongming 
Published: November 2017

AbstractMagnetic two-dimensional materials have attracted considerable attention for their significant potential application in spintronics. In this study, we present a high-quality Fe-doped SnS2 monolayer exfoliated using a micromechanical cleavage method. Fe atoms were doped at the Sn atom sites, and the Fe contents are ∼2.1%, 1.5%, and 1.1%. The field-effect transistors based on the Fe0.021Sn0.979S2 monolayer show n-type behavior and exhibit high optoelectronic performance. Magnetic measurements show that pure SnS2 is diamagnetic, whereas Fe0.021Sn0.979S2 exhibits ferromagnetic behavior with a perpendicular anisotropy at 2 K and a Curie temperature of ~31 K. Density functional theory calculations show that long-range ferromagnetic ordering in the Fe-doped SnS2 monolayer is energetically stable, and the estimated Curie temperature agrees well with the results of our experiment. The results suggest that Fe-doped SnS2 has significant potential in future nanoelectronic, magnetic, and optoelectronic applications.
Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy
Authors: Zhu Guizhi , Lynn Geoffrey M. , Jacobson Orit , Chen Kai , Liu Yi , Zhang Huimin , Ma Ying , Zhang Fuwu , Tian Rui , Ni Qianqian , Cheng Siyuan , Wang Zhantong , Lu Nan , Yung Bryant C. , Wang Zhe , Lang Lixin , Fu Xiao , Jin Albert , Weiss Ido D. , Vishwasrao Harshad , Niu Gang , Shroff Hari , Klinman Dennis M. , Seder Robert A. , Chen Xiaoyuan 
Published: November 2017

AbstractSubunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.
Initiation of prolyl cis-trans isomerisation in the CDR-H3 loop of an antibody in response to antigen binding
Authors: Shinoda Keiko , Fujitani Hideaki 
Published: November 2017

AbstractProline cis-trans isomerisation is a regulatory mechanism used in a range of biological processes, and is related to various diseases such as Alzheimers disease and cancer. However, the details of the exact molecular mechanism by which it occurs are not known. Using X-ray crystallography, proline isomerisation has been shown to occur following formation of an antigen-antibody complex between the target epiregulin (EPR) and the antibody 9E5, at proline (Pro103), located in the third complementarity-determining region (CDR) of the heavy chain of 9E5. To obtain an accurate description of the pathway involved in cis-trans isomerisation in this system, we performed ten independent long molecular dynamics (MD) simulations starting at a stable transient bound structure obtained from many short binding MD simulations. As a result, we were able to describe the process by which cis-trans isomerisation is initiated, and suggest a catalysis mechanism for cis-trans isomerization in this antigen-antibody system. We found that Asp102, which is immediately adjacent to Pro103, rotates while changing its interacting partner residues in the light chain of 9E5, and at the same time EPR polar residues help to stabilise the intermediate states in the isomerisation process by interacting strongly with Asp102.
Comprehensive statistical inference of the clonal structure of cancer from multiple biopsies
Authors: Liu Jie , Halloran John T. , Bilmes Jeffrey A. , Daza Riza M. , Lee Choli , Mahen Elisabeth M. , Prunkard Donna , Song Chaozhong , Blau Sibel , Dorschner Michael O. , Gadi Vijayakrishna K. , Shendure Jay , Blau C. Anthony , Noble William S. 
Published: November 2017

AbstractA comprehensive characterization of tumor genetic heterogeneity is critical for understanding how cancers evolve and escape treatment. Although many algorithms have been developed for capturing tumor heterogeneity, they are designed for analyzing either a single type of genomic aberration or individual biopsies. Here we present THEMIS (Tumor Heterogeneity Extensible Modeling via an Integrative System), which allows for the joint analysis of different types of genomic aberrations from multiple biopsies taken from the same patient, using a dynamic graphical model. Simulation experiments demonstrate higher accuracy of THEMIS over its ancestor, TITAN. The heterogeneity analysis results from THEMIS are validated with single cell DNA sequencing from a clinical tumor biopsy. When THEMIS is used to analyze tumor heterogeneity among multiple biopsies from the same patient, it helps to reveal the mutation accumulation history, track cancer progression, and identify the mutations related to treatment resistance. We implement our model via an extensible modeling platform, which makes our approach open, reproducible, and easy for others to extend.
Deconvoluting the Photonic and Electronic Response of 2D Materials: The Case of MoS2
Authors: Zhang Kehao , Borys Nicholas J. , Bersch Brian M. , Bhimanapati Ganesh R. , Xu Ke , Wang Baoming , Wang Ke , Labella Michael , Williams Teague A. , Haque Md Amanul. , Barnard Edward S. , Fullerton-Shirey Susan , Schuck P. James , Robinson Joshua A. 
Published: November 2017

AbstractEvaluating and tuning the properties of two-dimensional (2D) materials is a major focus of advancing 2D science and technology. While many claim that the photonic properties of a 2D layer provide evidence that the material is “high quality”, this may not be true for electronic performance. In this work, we deconvolute the photonic and electronic response of synthetic monolayer molybdenum disulfide. We demonstrate that enhanced photoluminescence can be robustly engineered via the proper choice of substrate, where growth of MoS2 on r-plane sapphire can yield >100x enhancement in PL and carrier lifetime due to increased molybdenum-oxygen bonding compared to that of traditionally grown MoS2 on c-plane sapphire. These dramatic enhancements in optical properties are similar to those of super-acid treated MoS2, and suggest that the electronic properties of the MoS2 are also superior. However, a direct comparison of the charge transport properties indicates that the enhanced PL due to increased Mo-O bonding leads to p-type compensation doping, and is accompanied by a 2x degradation in transport properties compared to MoS2 grown on c-plane sapphire. This work provides a foundation for understanding the link between photonic and electronic performance of 2D semiconducting layers, and demonstrates that they are not always correlated.
Network effects on coordination in asymmetric games
Authors: Broere Joris , Buskens Vincent , Weesie Jeroen , Stoof Henk 
Published: November 2017

AbstractNetwork structure can have an important effect on the behavior of players in an iterated 2 × 2 game. We study the effect of network structure on global and local behavior in asymmetric coordination games using best response dynamics. We find that global behavior is highly dependent on network topology. Random (Erdös-Rényi) networks mostly converge to homogeneous behavior, but the higher the clustering in the network the more heterogeneous the behavior becomes. Behavior within the communities of the network is almost exclusively homogeneous. The findings suggest that clustering of networks facilitates self-organization of uniform behavior within clusters, but heterogeneous behavior between clusters. At the local level we find that some nodes are more important in determining the equilibrium behavior than other nodes. Degree centrality is for most networks the main predictor for the behavior and nodes with an even degree have an advantage over nodes with an uneven degree in dictating the behavior. We conclude that the behavior is difficult to predict for (Erdös-Rényi) networks and that the network imposes the behavior as a function of clustering and degree heterogeneity in other networks.
Establishment of a strain of haemophilia-A pigs by xenografting of foetal testicular tissue from neonatally moribund cloned pigs
Authors: Kaneko Hiroyuki , Kikuchi Kazuhiro , Nakai Michiko , Fuchimoto Daiichiro , Suzuki Shunichi , Sembon Shoichiro , Noguchi Junko , Onishi Akira 
Published: November 2017

AbstractGrafting of testicular tissue into immunodeficient mice makes it possible to obtain functional sperm from immature donor animals that cannot be used for reproduction. We have developed a porcine model of human haemophilia A (haemophilia-A pigs) by nuclear transfer cloning from foetal fibroblasts after disruption of the X-linked coagulation factor VIII (F8) gene. Despite having a recessive condition, female F8+/− cloned pigs died of severe bleeding at an early age, as was the case for male F8−/Y cloned pigs, thus making it impossible to obtain progeny. In this study, therefore, we produced sperm from F8−/Y cloned pigs by grafting their foetal testicular tissue into nude mice. Two F8+/− female pigs were generated from oocytes injected with xenogeneic sperm. Unlike the F8+/− cloned pigs, they remained asymptomatic, and delivered five F8−/Y and four F8+/− pigs after being crossed with wild-type boars. The descendant F8−/Y pigs conserved the haemophilia phenotype. Thus, the present F8+/− pigs show resolution of the phenotypic abnormality, and will facilitate production of F8−/Y pigs as founders of a strain of haemophilia-A pigs for the development of new therapeutics for haemophilia A. This strategy will be applicable to other genetically modified pigs.
ATR-FTIR spectral discrimination between normal and tumorous mouse models of lymphoma and melanoma from serum samples
Authors: Ghimire Hemendra , Venkataramani Mahathi , Bian Zhen , Liu Yuan , Perera A. G. Unil 
Published: November 2017

AbstractThis study presents, attenuated total reflection Fourier transforms infrared spectroscopy of dried serum samples in an effort to assess biochemical changes induced by non-Hodgkin’s lymphoma and subcutaneous melanoma. An EL4 mouse model of non-Hodgkin lymphoma and a B16 mouse model of subcutaneous melanoma are used to extract a snapshot of tumor-associated alteration in the serum. The study of both cancer-bearing mouse models in wild types and their corresponding control types, emphasizes the diagnostic potential of this approach as a screening technique for non-Hodgkin lymphoma and melanoma skin cancer. Infrared absorbance values of the different spectral bands, hierarchical clustering and integral values of the component bands by curve fitting, show statistically significant differences (student’s t-test, two-tailed unequal variance p-value < 0.05) between spectra representing healthy and tumorous mouse. This technique may thus be useful for having individualized route maps for rapid evaluation of lymphoma and melanoma status and associated therapeutic modalities.
Coupling of sea level and tidal range changes, with implications for future water levels
Authors: Devlin Adam T. , Jay David A. , Talke Stefan A. , Zaron Edward D. , Pan Jiayi , Lin Hui 
Published: November 2017

AbstractAre perturbations to ocean tides correlated with changing sea-level and climate, and how will this affect high water levels? Here, we survey 152 tide gauges in the Pacific Ocean and South China Sea and statistically evaluate how the sum of the four largest tidal constituents, a proxy for the highest astronomical tide (HAT), changes over seasonal and interannual time scales. We find that the variability in HAT is significantly correlated with sea-level variability; approximately 35% of stations exhibit a greater than ±50 mm tidal change per meter sea-level fluctuation. Focusing on a subset of three stations with long records, probability density function (PDF) analyses of the 95% percentile exceedance of total sea level (TSL) show long-term changes of this high-water metric. At Hong Kong, the increase in tides significantly amplifies the risk caused by sea-level rise. Regions of tidal decrease and/or amplification highlight the non-linear response to sea-level variations, with the potential to amplify or mitigate against the increased flood risk caused by sea-level rise. Overall, our analysis suggests that in many regions, local flood level determinations should consider the joint effects of non-stationary tides and mean sea level (MSL) at multiple time scales.
Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?
Authors: Magalhães Pedro , Pejchinovski Martin , Markoska Katerina , Banasik Miroslaw , Klinger Marian , Švec-Billá Dominika , Rychlík Ivan , Rroji Merita , Restivo Arianna , Capasso Giovambattista , Bob Flaviu , Schiller Adalbert , Ortiz Alberto , Perez-Gomez Maria Vanessa , Cannata Pablo , Sanchez-Niño Maria Dolores , Naumovic Radomir , Brkovic Voin , Polenakovic Momir , Mullen William , Vlahou Antonia , Zürbig Petra , Pape Lars , Ferrario Franco , Denis Colette , Spasovski Goce , Mischak Harald , Schanstra Joost P. 
Published: November 2017

AbstractChronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho = 0.430, P = 0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho = −0.222; −0.137; −0.070 and P = 0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials.
Plant-endophytes interaction influences the secondary metabolism in Echinacea purpurea (L.) Moench: an in vitro model
Authors: Maggini Valentina , De Leo Marinella , Mengoni Alessio , Gallo Eugenia Rosaria , Miceli Elisangela , Reidel Rose Vanessa Bandeira , Biffi Sauro , Pistelli Luisa , Fani Renato , Firenzuoli Fabio , Bogani Patrizia 
Published: November 2017

AbstractThe influence of the interaction(s) between the medicinal plant Echinacea purpurea (L.) Moench and its endophytic communities on the production of alkamides is investigated. To mimic the in vivo conditions, we have set up an infection model of axenic in vitro E. purpurea plants inoculated with a pool of bacterial strains isolated from the E. purpurea stems and leaves. Here we show different alkamide levels between control (not-inoculated) and inoculated plants, suggesting that the alkamide biosynthesis may be modulated by the bacterial infection. Then, we have analysed the branched-chain amino acids (BCCA) decarboxylase gene (GenBank Accession #LT593930; the enzymatic source for the amine moiety formation of the alkamides) expression patterns. The expression profile shows a higher expression level in the inoculated E. purpurea tissues than in the control ones. These results suggest that the plant-endophyte interaction can influence plant secondary metabolism affecting the therapeutic properties of E. purpurea.
Fe4S4 Cubane Type Cluster Immobilized on a Graphene Support: A High Performance H2 Evolution Catalysis in Acidic Water
Authors: Begum Ameerunisha , Sheikh Aasif Hassan , Moula Golam , Sarkar Sabyasachi 
Published: November 2017

AbstractThe development of alternate catalysts that utilize non-precious metal based electrode materials such as the first row transition metal complexes is an important goal for economic fuel cell design. In this direction, a new Fe4S4 cubane type cluster, [PPh4]2[Fe4S4(DMET)4] (1) (DMET = cis-1,2-dicarbomethoxyethylene dithiolate) and its composite with functionalized graphene, (1@graphene) have been synthesized and characterized. The presence of nanocrystalline structures on graphene matrix in TEM and SEM images of 1@graphene indicate that the cluster (1) has been immobilized. The composite, 1@graphene evolves H2 gas from p-toluene sulfonic acid (TsOH) in a mixture of H2O and CH3CN under ambient conditions with a significant turnover number of 3200. 1@graphene electro-catalyzes H2 evolution at Ep, −1.2 V with remarkable throughput, catalytic efficiency and stability in only H2O or in only CH3CN. The Fe4S4 cluster (1) alone electro-catalyzes hydrogen evolution at Ep, −0.75 V from TsOH in CH3CN. The X-ray crystal structure of the Fe4S4 cluster (1) (λmax, CH2Cl2, 823 nm; ε, 2200 mol−1 cm−1) shows that it is dianionic with a cumulative oxidation state of +2.5 for the iron centers and short C-S bond distances (ca., 1.712 Å & 1.727 Å) indicating the presence of sulfur based radicals.
Cdc7-Dbf4-mediated phosphorylation of HSP90-S164 stabilizes HSP90-HCLK2-MRN complex to enhance ATR/ATM signaling that overcomes replication stress in cancer
Authors: Cheng An Ning , Fan Chi-Chen , Lo Yu-Kang , Kuo Cheng-Liang , Wang Hui-Chun , Lien I.-Hsin , Lin Shu-Yu , Chen Chung-Hsing , Jiang Shih Sheng , Chang I.-Shou , Juan Hsueh-Fen , Lyu Ping-Chiang , Lee Alan Yueh-Luen 
Published: November 2017

AbstractCdc7-Dbf4 kinase plays a key role in the initiation of DNA replication and contributes to the replication stress in cancer. The activity of human Cdc7-Dbf4 kinase remains active and acts as an effector of checkpoint under replication stress. However, the downstream targets of Cdc7-Dbf4 contributed to checkpoint regulation and replication stress-support function in cancer are not fully identified. In this work, we showed that aberrant Cdc7-Dbf4 induces DNA lesions that activate ATM/ATR-mediated checkpoint and homologous recombination (HR) DNA repair. Using a phosphoproteome approach, we identified HSP90-S164 as a target of Cdc7-Dbf4 in vitro and in vivo. The phosphorylation of HSP90-S164 by Cdc7-Dbf4 is required for the stability of HSP90-HCLK2-MRN complex and the function of ATM/ATR signaling cascade and HR DNA repair. In clinically, the phosphorylation of HSP90-S164 indeed is increased in oral cancer patients. Our results indicate that aberrant Cdc7-Dbf4 enhances replication stress tolerance by rewiring ATR/ATM mediated HR repair through HSP90-S164 phosphorylation and by promoting recovery from replication stress. We provide a new solution to a subtyping of cancer patients with dominant ATR/HSP90 expression by combining inhibitors of ATR-Chk1, HSP90, or Cdc7 in cancer combination therapy.
QSKL protects against myocardial apoptosis on heart failure via PI3K/Akt-p53 signaling pathway
Authors: Chang Hong , Li Chun , Wang Qiyan , Lu Linghui , Zhang Qian , Zhang Yi , Zhang Na , Wang Yong , Wang Wei 
Published: November 2017

AbstractThe ancient traditional Chinese medicine Qishenkeli (QSKL) is widely used in the treatment of heart failure (HF) in China. Previous studies have shown that QSKL has definite effects on HF. The purpose of this study is to identify the regulation of QSKL on apoptosis and clarify the underlying mechanism. An apoptosis model of H9C2 cells was induced by oxygen-glucose deprivation/recovery (OGD/R). An animal model of HF was induced by ligation of left anterior descending (LAD) coronary artery in rat. We found that QSKL reduced intracellular ROS generation, increased mitochondrial membrane potential and protected H9C2 cells against OGD/R-induced apoptosis. In vivo results showed that QSKL administration could improve cardiac functions, decrease fibrotic area, infarct size and apoptotic rate in HF model. QSKL regulated the expressions of key apoptotic molecules, including increasing Bcl-2/Bax ratio, reducing the expressions of P53, Bax and Cleaved-caspase-3. Interestingly, QSKL also regulated the phosphorylated expressions of PI3K and Akt without significantly affecting PTEN. Taken together, the protective and anti-apoptotic effects of QSKL could be mediated partly through modulating the PI3K/Akt-P53 apoptotic pathway.