bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis
Authors: Le Chevalier Fabien , Cascioferro Alessandro , Frigui Wafa , Pawlik Alexandre , Boritsch Eva C. , Bottai Daria , Majlessi Laleh , Herrmann Jean Louis , Brosch Roland 
Published: November 2015

AbstractMycobacterium tuberculosis, the agent of human tuberculosis has developed different virulence mechanisms and virulence-associated tools during its evolution to survive and multiply inside the host. Based on previous reports and by analogy with other bacteria, phospholipases C (PLC) of M. tuberculosis were thought to be among these tools. To get deeper insights into the function of PLCs, we investigated their putative involvement in the intracellular lifestyle of M. tuberculosis, with emphasis on phagosomal rupture and virulence, thereby re-visiting a research theme of longstanding interest. Through the construction and use of an M. tuberculosis H37Rv PLC-null mutant (ΔPLC) and control strains, we found that PLCs of M. tuberculosis were not required for induction of phagosomal rupture and only showed marginal, if any, impact on virulence of M. tuberculosis in the cellular and mouse infection models used in this study. In contrast, we found that PLC-encoding genes were strongly upregulated under phosphate starvation and that PLC-proficient M. tuberculosis strains survived better than ΔPLC mutants under conditions where phosphatidylcholine served as sole phosphate source, opening new perspectives for studies on the role of PLCs in the lifecycle of M. tuberculosis.
Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma
Authors: Yu Diana , Kahen Elliot , Cubitt Christopher L. , McGuire Jeremy , Kreahling Jenny , Lee Jae , Altiok Soner , Lynch Conor C. , Sullivan Daniel M. , Reed Damon R. 
Published: November 2015

AbstractSystemic therapy has improved osteosarcoma event-free and overall survival, but 30–50% of patients originally diagnosed will have progressive or recurrent disease, which is difficult to cure. Osteosarcoma has a complex karyotype, with loss of p53 in the vast majority of cases and an absence of recurrent, targetable pathways. In this study, we explored 54 agents that are clinically approved for other oncologic indications, agents in active clinical development and others with promising preclinical data in osteosarcoma at clinically achievable concentrations in 5 osteosarcoma cell lines. We found significant single-agent activity of multiple agents and tested 10 drugs in all permutations of two-drug combinations to define synergistic combinations by Chou and Talalay analysis. We then evaluated order of addition to choose the combinations that may be best to translate to the clinic. We conclude that the repurposing of chemotherapeutics in osteosarcoma by using an in vitro system may define novel drug combinations with significant in vivo activity. In particular, combinations of proteasome inhibitors with histone deacetylase inhibitors and ixabepilone and MK1775 demonstrated excellent activity in our assays.
Polymorphisms near the IFNL3 Gene Associated with HCV RNA Spontaneous Clearance and Hepatocellular Carcinoma Risk
Authors: Lee Mei-Hsuan , Yang Hwai-I , Lu Sheng-Nan , Lin Yu-Ju , Jen Chin-Lan , Wong Kang-Hsuan , Chan Soa-Yu , Chen Liang-Chun , Wang Li-Yu , L’Italien Gilbert , Yuan Yong , Chen Chien-Jen 
Published: November 2015

AbstractThe aims of this study were to investigate associations between single nucleotide polymorphisms (SNPs) near the genes IFNL2, IFNL3 and IFNL4 and spontaneous clearance of hepatitis C virus (HCV) and to evaluate variants for their risk of hepatocellular carcinoma (HCC) among subjects in whom spontaneous HCV RNA clearance did not occur. In the first study, 889 untreated anti-HCV-seropositive patients without HCC symptoms were followed from 1991 to 2005. The spontaneous HCV clearance rate was found to be 33.1%. The TT variant of rs8099917 near IFNL3 was associated with increased spontaneous HCV RNA clearance, with an adjusted odds ratio (95% CI) of 2.78 (1.43–5.39), as was the newly-identified TT/TT dinucleotide variant rs368234815 near IFNL4 (adjusted odds ratio 2.68, 95% CI: 1.42–5.05). In the second study, associations between SNPs and HCC risk were examined in 483 HCC cases with detectable HCV RNA and 516 controls. In participants with HCV genotype 1, unfavorable genotypes for HCV clearance near IFNL3were associated with increased HCC risk, the adjusted odds ratio (95% CI) for rs12979860 and rs8099917 being 1.73 (1.00–2.99) and 1.84 (1.02–3.33), respectively. Host characteristics should be considered to identify high-risk patients to prioritize the use of new antiviral agents and intensive screening.
Phenotypic and genomic comparisons of highly vancomycin-resistant Staphylococcus aureus strains developed from multiple clinical MRSA strains by in vitro mutagenesis
Authors: Ishii Kenichi , Tabuchi Fumiaki , Matsuo Miki , Tatsuno Keita , Sato Tomoaki , Okazaki Mitsuhiro , Hamamoto Hiroshi , Matsumoto Yasuhiko , Kaito Chikara , Aoyagi Tetsuji , Hiramatsu Keiichi , Kaku Mitsuo , Moriya Kyoji , Sekimizu Kazuhisa 
Published: November 2015

AbstractThe development of vancomycin (VCM) resistance in Staphylococcus aureus threatens global health. Studies of the VCM-resistance mechanism and alternative therapeutic strategies are urgently needed. We mutagenized S. aureus laboratory strains and methicillin-resistant S. aureus (MRSA) with ethyl methanesulfonate and isolated mutants that exhibited high resistance to VCM (minimum inhibitory concentration = 32 μg/ml). These VCM-resistant strains were sensitive to linezolid and rifampicin and partly to arbekacin and daptomycin. Beta-lactams had synergistic effects with VCM against these mutants. VCM-resistant strains exhibited a 2-fold increase in the cell wall thickness. Several genes were commonly mutated among the highly VCM-resistant mutants. These findings suggest that MRSA has a potential to develop high VCM resistance with cell wall thickening by the accumulation of mutations.
Body visual discontinuity affects feeling of ownership and skin conductance responses
Authors: Tieri Gaetano , Tidoni Emmanuele , Pavone Enea Francesco , Aglioti Salvatore Maria 
Published: November 2015

AbstractWhen we look at our hands we are immediately aware that they belong to us and we rarely doubt about the integrity, continuity and sense of ownership of our bodies. Here we explored whether the mere manipulation of the visual appearance of a virtual limb could influence the subjective feeling of ownership and the physiological responses (Skin Conductance Responses, SCRs) associated to a threatening stimulus approaching the virtual hand. Participants observed in first person perspective a virtual body having the right hand-forearm (i) connected by a normal wrist (Full-Limb) or a thin rigid wire connection (Wire) or (ii) disconnected because of a missing wrist (m-Wrist) or a missing wrist plus a plexiglass panel positioned between the hand and the forearm (Plexiglass). While the analysis of subjective ratings revealed that only the observation of natural full connected virtual limb elicited high levels of ownership, high amplitudes of SCRs were found also during observation of the non-natural, rigid wire connection condition. This result suggests that the conscious embodiment of an artificial limb requires a natural looking visual body appearance while implicit reactivity to threat may require physical body continuity, even non-naturally looking, that allows the implementation of protective reactions to threat.
Nanomechanical characterization of nanostructured bainitic steel: Peak Force Microscopy and Nanoindentation with AFM
Authors: Morales-Rivas Lucia , González-Orive Alejandro , Garcia-Mateo Carlos , Hernández-Creus Alberto , Caballero Francisca G. , Vázquez Luis 
Published: November 2015

AbstractThe full understanding of the deformation mechanisms in nanostructured bainite requires the local characterization of its mechanical properties, which are expected to change from one phase, bainitic ferrite, to another, austenite. This study becomes a challenging process due to the bainitic nanostructured nature and high Young’s modulus. In this work, we have carried out such study by means of the combination of AFM-based techniques, such as nanoindentation and Peak Force Quantitative Nanomechanical Mapping (PF-QNM) measurements. We have addressed critically the limits and advantages of these techniques and been able to measure some elastoplastic parameters of both phases. Specifically, we have analyzed by PF-QNM two nanostructured bainitic steels, with a finer and a coarser structure and found that both phases have a similar Young’s modulus.
Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E
Authors: Ni Yinhua , Nagashimada Mayumi , Zhuge Fen , Zhan Lili , Nagata Naoto , Tsutsui Akemi , Nakanuma Yasuni , Kaneko Shuichi , Ota Tsuguhito 
Published: November 2015

AbstractHepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4+ and CD8+ T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH.
Bacterial diversity is strongly associated with historical penguin activity in an Antarctic lake sediment profile
Authors: Zhu Renbin , Shi Yu , Ma Dawei , Wang Can , Xu Hua , Chu Haiyan 
Published: November 2015

AbstractCurrent penguin activity in Antarctica affects the geochemistry of sediments and their microbial communities; the effects of historical penguin activity are less well understood. Here, bacterial diversity in ornithogenic sediment was investigated using high-throughput pyrosequencing. The relative abundances of dominant phyla were controlled by the amount of historical penguin guano deposition. Significant positive correlations were found between both the bacterial richness and diversity and the relative penguin number (p < 0.01); this indicated that historical penguin activity drove the vertical distribution of the bacterial communities. The lowest relative abundances of individual phyla corresponded to lowest number of penguin population at 1,800–2,300 yr BP during a drier and colder period; the opposite was observed during a moister and warmer climate (1,400–1,800 yr BP). This study shows that changes in the climate over millennia affected penguin populations and the outcomes of these changes affect the sediment bacterial community today.
An Insight into Recombination with Enterovirus Species C and Nucleotide G-480 Reversion from the Viewpoint of Neurovirulence of Vaccine-Derived Polioviruses
Authors: Zhang Yong , Yan Dongmei , Zhu Shuangli , Nishimura Yorihiro , Ye Xufang , Wang Dongyan , Jorba Jaume , Zhu Hui , An Hongqiu , Shimizu Hiroyuki , Kew Olen , Xu Wenbo 
Published: November 2015

AbstractA poliomyelitis outbreak caused by type 1 circulating vaccine-derived polioviruses (cVDPVs) was identified in China in 2004. Six independent cVDPVs (eight isolates) could be grouped into a single cluster with pathways of divergence different from a single cVDPV progenitor, which circulated and evolved into both a highly neurovirulent lineage and a less neurovirulent lineage. They were as neurovirulent as the wild type 1 Mahoney strain, recombination was absent and their nucleotide 480-G was identical to that of the Sabin strain. The Guizhou/China cVDPV strains shared 4 amino acid replacements in the NAg sites: 3 located at the BC loop, which may underlie the aberrant results of the ELISA intratypic differentiation (ITD) test. The complete ORF tree diverged into two main branches from a common ancestral infection estimated to have occurred in about mid-September 2003, nine months before the appearance of the VDPV case, which indicated recently evolved VDPV. Further, recombination with species C enteroviruses may indicate the presence and density of these enteroviruses in the population and prolonged virus circulation in the community. The aforementioned cVDPVs has important implications in the global initiative to eradicate polio: high quality surveillance permitted earliest detection and response.
Abnormal pancreatic enzymes and their prognostic role after acute paraquat poisoning
Authors: Li Yi , Wang Meng , Gao Yanxia , Yang Wen , Xu Qun , Eddleston Michael , Li Li , Yu Xuezhong 
Published: November 2015

AbstractIngestion of paraquat causes multi-organ failure. Prognosis is best estimated through measurement of blood paraquat concentrations but this facility is not available in most hospitals. We studied the prognostic significance of abnormal pancreatic enzymes for survival. Patients with acute paraquat poisoning were recruited. An extensive series of blood tests including serum amylase were serially checked. Patients were sorted according to their serum amylase activity (normal [<220 U/L], mildly elevated [220 to 660 U/L], elevated [>660 U/L]) and survival compared between groups. 177 patients were enrolled to the study, of whom 67 died and 110 survived. 122 (70.62%), 27 (15.25%) and 25 (14.13%) patients were in the normal, mildly elevated and elevated amylase activity groups, respectively. The case fatality in the elevated group was 100% compared to 17% in the normal group (P < 0.001). We found four independent factors for paraquat death prediction: amylase, PaCO2, leukocyte number, and neutrophil percentage. Models using pancreatic enzyme activity showed good prediction power. We have found that abnormal pancreatic enzymes are useful prognostic marker of death after acute paraquat poisoning. Including serum amylase activity into a prognostic model provides a good prognostication.
Compatibility between mitochondrial and nuclear genomes correlates with the quantitative trait of lifespan in Caenorhabditis elegans
Authors: Zhu Zuobin , Lu Qing , Zeng Fangfang , Wang Junjing , Huang Shi 
Published: November 2015

AbstractMutations in mitochondrial genome have epistatic effects on organisms depending on the nuclear background, but a role for the compatibility of mitochondrial-nuclear genomes (mit-n) in the quantitative nature of a complex trait remains unexplored. We studied a panel of recombinant inbred advanced intercrossed lines (RIAILs) of C. elegans that were established from a cross between the N2 and HW strains. We determined the HW nuclear genome content and the mitochondrial type (HW or N2) of each RIAIL strain. We found that the degree of mit-n compatibility was correlated with the lifespans but not the foraging behaviors of RIAILs. Several known aging-associated QTLs individually showed no relationship with mitotypes but collectively a weak trend consistent with a role in mit-n compatibility. By association mapping, we identified 293 SNPs that showed linkage with lifespan and a relationship with mitotypes consistent with a role in mit-n compatibility. We further found an association between mit-n compatibility and several functional characteristics of mitochondria as well as the expressions of genes involved in the respiratory oxidation pathway. The results provide the first evidence implicating mit-n compatibility in the quantitative nature of a complex trait and may be informative to certain evolutionary puzzles on hybrids.
Fluidic Grooves on Doped-Ice Surface as Size-Tunable Channels
Authors: Inagawa Arinori , Harada Makoto , Okada Tetsuo 
Published: November 2015

AbstractWe propose a new principle for fabrication of size-tunable fluidic nano- and microchannels with a ubiquitous green material, water. Grooves filled with a solution are spontaneously formed on the surface of ice when an appropriate dopant is incorporated. Sucrose doping allows the development of grooves with lengths of 300 μm along the boundaries of ice crystal grains. This paper focuses on controlling the size of the liquid-filled groove and reveals its applicability to size-selective differentiation of nano- and micromaterials. The width of this groove can be varied in a range of 200 nm to 4 μm by adjusting the working temperature of the frozen platform. The channel dimension is reproducible as long as the same frozen condition is employed. We demonstrate the size-selective entrapment of particles as well as the state evaluation of DNA by controlling the physical interference of the ice wall with the electrophoretic migration of particles.
Resistive interchange mode destabilized by helically trapped energetic ions and its effects on energetic ions and bulk plasma in a helical plasma
Authors: Du X.D. , Toi K. , Ohdachi S. , Osakabe M. , Ido T. , Tanaka K. , Yokoyama M. , Yoshinuma M. , Ogawa K. , Watanabe K.Y. , Akiyama T. , Isobe M. , Nagaoka K. , Ozaki T. , Sakakibara S. , Seki R. , Shimizu A. , Suzuki Y. , Tsuchiya H. 
Published: November 2015

Abstract
A resistive interchange mode of the

structure (

,

: poloidal and toroidal mode numbers, respectively) with a bursting character and rapid frequency chirping in the range less than 10 kHz is observed for the first time in the edge region of the net current-free, low beta LHD (Large Helical Device) plasmas during high power injection of perpendicular neutral beams. The mode resonates with the precession motion of helically trapped energetic ions (EPs), following the resonant condition. The radial mode structure is recognized to be similar to that of the pressure-driven resistive interchange mode, of which radial displacement eigenfunction quite localizes around the mode rational surface, and evolves into an odd-type (or island-type) during the late of frequency chirping phase. This beam driven mode is excited when the beta value of helically trapped EPs exceeds a certain threshold. This instability is thought to be a new branch of resistive interchange mode destabilized by the trapped energetic ions. The radial transport, i.e. redistribution and losses, of helically trapped energetic ions induced by the mode transiently generates significant radial electric field near the plasma peripheral region. The large shear of thus generated radial electric field is thought to contribute to the observed suppression of micro-turbulence and transient increases of the temperature of fully ionized carbon impurity ions and electron density, suggesting improvement of bulk plasma confinement.
Interaction of deuterium plasma with sputter-deposited tungsten nitride films
Authors: Gao L. , Jacob W. , Meisl G. , Schwarz-Selinger T. , Höschen T. , von Toussaint U. , Dürbeck T. 
Published: November 2015

Abstract
Magnetron-sputtered tungsten nitride (WN
x
) films were used as a model system to study the behaviour of re-deposited WN
x
layers which could form in fusion devices with tungsten (W) wall during nitrogen seeding. The interaction of such WN
x
layers with deuterium (D) plasmas was investigated in dedicated laboratory experiments. D retention and N removal due to D plasma exposure (D flux: 9.9  ×  1019 D m−2 s−1, ion energy 215 eV) at different temperatures were measured with ion beam analysis (IBA). Low-energy argon sputtering followed by IBA was applied to resolve the D distribution in the top-most surface of WN
x
with significantly improved depth resolution compared with the standard D depth profiling method by nuclear reaction analysis. Experimentally determined thicknesses for the penetration of D in WN
x
were compared with the penetration depth for D calculated in SDTrimSP simulations. Results show that D is only retained within the ion penetration range for samples exposed at 300 K. In contrast to the 300 K case, D diffuses beyond the implantation depth in a sample exposed at 600 K. However, the D penetration depth is much lower than in pure W at comparable conditions. The total amount of retained D in WN
x
at 600 K is by 50% lower than for implantation at 300 K with the same D fluence. Nitrogen is removed only within the D ion range.
Characterisation of the L-mode scrape off layer in MAST: decay lengths
Authors: Militello F. , Garzotti L. , Harrison J. , Omotani J.T. , Scannell R. , Allan S. , Kirk A. , Lupelli I. , Thornton A.J. 
Published: November 2015

Abstract
This work presents a detailed characterisation of the MAST Scrape Off Layer in L-mode. Scans in line averaged density, plasma current and toroidal magnetic field were performed. A comprehensive and integrated study of the SOL was allowed by the use of a wide range of diagnostics. In agreement with previous results, an increase of the line averaged density induced a broadening of the midplane density profile. This increase was not correlated with divertor detachment, as confirmed by the systematic increase of the target ion flux and decrease of the

emission. Also, no clear correlation is found with the density of the neutral particles at the wall. At comparable density levels, discharges with higher current did not show broadening. Outer target ion saturation current and heat flux decay lengths were measured and compared with midplane data. For the saturation current, the upstream projections of the target values, based on diffusive models, did not match the midplane measurements, neither in amplitude nor in trend, while agreement was found for the heat fluxes, suggesting a different perpendicular transport mechanism for the two channels. Furthermore, the value of the target heat flux decay length was quite insensitive to changes in the thermodynamic conditions, in agreement with recent scaling laws. In all the cases studied, sawtooth oscillations were present but they simply rescaled self-similarly the target profiles. The separatrix conditions changed significantly during a sawtooth cycle, but the target heat flux decay length and divertor spreading factor remained nearly constant, indicating that these quantities are rather insensitive to the upstream thermodynamic state of the SOL.