bluuebunny/crossref_metadata_2025_split huggingface dataset:
The determinant of periodicity in Mycoplasma pneumoniae incidence: an insight from mathematical modelling
Authors: Omori Ryosuke , Nakata Yukihiko , Tessmer Heidi L. , Suzuki Satowa , Shibayama Keigo 
Published: September 2015

AbstractUntil the early 1990s, incidences of Mycoplasma pneumoniae (MP) infection showed three to five year epidemic cycles in multiple countries, however, the mechanism for the MP epidemic cycle has not been understood. Here, we investigate the determinant of periodicity in MP incidence by employing a mathematical model describing MP transmission dynamics. Three candidates for the determinant of periodicity were evaluated: school-term forcing, minor variance in the duration of immunity and epidemiological interference between MP serotypes. We find that minor variation in the duration of immunity at the population level must be considered essential for the MP epidemic cycle because the MP cyclic incidence pattern did not replicate without it. Minor variation, in this case, is a less dispersed distribution for the duration of immunity than an exponential distribution. Various lengths of epidemic cycles, including cycles typically found in nature, e.g. three to five year cycles, were also observed when there was minor variance in the duration of immunity. The cyclic incidence pattern is robust even if there is epidemiological interference due to cross-immune protection, which is observed in the epidemiological data as negative correlation between epidemics per MP serotype.
Expression of IL-37 contributes to the immunosuppressive property of human CD4+CD25+ regulatory T cells
Authors: Shuai Xu , Wei-min Li , Tong Ya-lin , Dong Ning , Sheng Zhi-yong , Yao Yong-ming 
Published: September 2015

AbstractInterleukin-37 (IL-37) possesses the function of down-regulate systemic and local inflammation. It is unknown whether IL-37 is expressed in human regulatory T cells (Tregs) and its role in modulating the immune response of Tregs. In the present study, cell surface molecules and secretory cytokines were analyzed in order to determine the function of IL-37 in regulating inhibitory effect of human CD4+CD25+Tregs. Meanwhile, the effects of IL-37 on T cell differentiation and proliferation as co-culture of CD4+CD25+Treg/CD4+CD25−T cell were also investigated. It was showed that IL-37 was expressed in cytoplasm of CD4+CD25+Tregs and the levels of IL-37 were gradually elevated with the enhanced activity of CD4+CD25+Tregs. Secretory cytokines such as transforming growth factor (TGF)-β and interleukin (IL)-10 and expressions of cell surface molecules, including forkhead/winged helix transcription factor p3 (FOXP3) and cytotoxic T-lymphocyte associated antigen (CTLA)-4, were significantly decreased when IL-37 gene was silenced by siRNA. Furthermore, down-regulation of IL-37 expression in human CD4+CD25+Tregs obviously promoted proliferation of co-cultured T cell and differentiation, together with observably enhancement of IL-2 formation. These results demonstrated that IL-37 might manifest as a critical protein involving in immunosuppression of human CD4+CD25+Tregs.
Activated WNT signaling in postnatal SOX2-positive dental stem cells can drive odontoma formation
Authors: Xavier Guilherme M. , Patist Amanda L. , Healy Chris , Pagrut Ankita , Carreno Gabriela , Sharpe Paul T. , Pedro Martinez-Barbera Juan , Thavaraj Selvam , Cobourne Martyn T. , Andoniadou Cynthia L. 
Published: September 2015

AbstractIn common with most mammals, humans form only two dentitions during their lifetime. Occasionally, supernumerary teeth develop in addition to the normal complement. Odontoma represent a small group of malformations containing calcified dental tissues of both epithelial and mesenchymal origin, with varying levels of organization, including tooth-like structures. The specific cell type responsible for the induction of odontoma, which retains the capacity to re-initiate de novo tooth development in postnatal tissues, is not known. Here we demonstrate that aberrant activation of WNT signaling by expression of a non-degradable form of β-catenin specifically in SOX2-positive postnatal dental epithelial stem cells is sufficient to generate odontoma containing multiple tooth-like structures complete with all dental tissue layers. Genetic lineage-tracing confirms that odontoma form in a similar manner to normal teeth, derived from both the mutation-sustaining epithelial stem cells and adjacent mesenchymal tissues. Activation of the WNT pathway in embryonic SOX2-positive progenitors results in ectopic expression of secreted signals that promote odontogenesis throughout the oral cavity. Significantly, the inductive potential of epithelial dental stem cells is retained in postnatal tissues and up-regulation of WNT signaling specifically in these cells is sufficient to promote generation and growth of ectopic malformations faithfully resembling human odontoma.
Leveraging long read sequencing from a single individual to provide a comprehensive resource for benchmarking variant calling methods
Authors: Mu John C. , Tootoonchi Afshar Pegah , Mohiyuddin Marghoob , Chen Xi , Li Jian , Bani Asadi Narges , Gerstein Mark B. , Wong Wing H. , Lam Hugo Y. K. 
Published: September 2015

AbstractA high-confidence, comprehensive human variant set is critical in assessing accuracy of sequencing algorithms, which are crucial in precision medicine based on high-throughput sequencing. Although recent works have attempted to provide such a resource, they still do not encompass all major types of variants including structural variants (SVs). Thus, we leveraged the massive high-quality Sanger sequences from the HuRef genome to construct by far the most comprehensive gold set of a single individual, which was cross validated with deep Illumina sequencing, population datasets and well-established algorithms. It was a necessary effort to completely reanalyze the HuRef genome as its previously published variants were mostly reported five years ago, suffering from compatibility, organization and accuracy issues that prevent their direct use in benchmarking. Our extensive analysis and validation resulted in a gold set with high specificity and sensitivity. In contrast to the current gold sets of the NA12878 or HS1011 genomes, our gold set is the first that includes small variants, deletion SVs and insertion SVs up to a hundred thousand base-pairs. We demonstrate the utility of our HuRef gold set to benchmark several published SV detection tools.
O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling
Authors: Shi Jianhua , Gu Jin-hua , Dai Chun-ling , Gu Jianlan , Jin Xiaoxia , Sun Jianming , Iqbal Khalid , Liu Fei , Gong Cheng-Xin 
Published: September 2015

AbstractApoptosis plays an important role in neural development and neurological disorders. In this study, we found that O-GlcNAcylation, a unique protein posttranslational modification with O-linked β-N-acetylglucosamine (GlcNAc), promoted apoptosis through attenuating phosphorylation/activation of AKT and Bad. By using co-immunoprecipitation and mutagenesis techniques, we identified O-GlcNAc modification at both Thr308 and Ser473 of AKT. O-GlcNAcylation-induced apoptosis was attenuated by over-expression of AKT. We also found a dynamic elevation of protein O-GlcNAcylation during the first four hours of cerebral ischemia, followed by continuous decline after middle cerebral artery occlusion (MCAO) in the mouse brain. The elevation of O-GlcNAcylation coincided with activation of cell apoptosis. Finally, we found a negative correlation between AKT phosphorylation and O-GlcNAcylation in ischemic brain tissue. These results indicate that cerebral ischemia induces a rapid increase of O-GlcNAcylation that promotes apoptosis through down-regulation of AKT activity. These findings provide a novel mechanism through which O-GlcNAcylation regulates ischemia-induced neuronal apoptosis through AKT signaling.
Ag@Au core-shell dendrites: a stable, reusable and sensitive surface enhanced Raman scattering substrate
Authors: Jun Yin Hong , Yang Chen Zhao , Mei Zhao Yong , Yang Lv Ming , An Shi Chun , Long Wu Zheng , Zhang Xin , Liu Luo , Li Wang Ming , Jun Xu Hai 
Published: September 2015

AbstractSurface enhanced Raman scattering (SERS) substrate based on fabricated Ag@Au core-shell dendrite was achieved. Ag dendrites were grown on Si wafer by the hydrothermal corrosion method and Au nanofilm on the surface of Ag dendritic nanostructure was then fabricated by chemical reduction. With the help of sodium borohydride in water, Au surface absorbates such as thiophene, adenine, rhodamine, small anions (Br– and I–) and a polymer (PVP, poly(N-vinylpyrrolidone)) can be completely and rapidly removed. After four repeatable experiments, the substrate SERS function did not decrease at all, indicating that the Ag@Au dendrite should be of great significance to SERS application because it can save much resource. Six-month-duration stability tests showed that the Ag@Au core-shell dendrite substrate is much more stable than the Ag dendrite substrates. We have also experimented on fast detection of Cd2+ at 10−8  M concentration by decorating single-stranded DNA containing adenine and guanine bases on the surface of this Ag@Au dendrite. Finite-difference time-domain simulations were carried out to investigate the influence of Au nanolayer on Ag dendrites, which showed that the local electric fields and enhancement factor are hardly affected when a 4 nm Au nanolayer is coated on Ag dendrite surface.
Recombinant human endostatin enhances the radioresponse in esophageal squamous cell carcinoma by normalizing tumor vasculature and reducing hypoxia
Authors: Zhu Hongcheng , Yang Xi , Ding Yuqiong , Liu Jia , Lu Jing , Zhan Liangliang , Qin Qin , Zhang Hao , Chen Xiaochen , Yang Yuehua , Yang Yan , Liu Zheming , Yang Meiling , Zhou Xifa , Cheng Hongyan , Sun Xinchen 
Published: September 2015

AbstractThe aim of this study was to investigate the effect of recombinant human endostatin (rh-Endo) in combination with radiation therapy (RT) on esophageal squamous cell carcinoma (ESCC) and explore the potential mechanisms. ECA109-bearing nude mice were administered RT and/or rh-Endo treatment. Tumor volume, survival, hypoxia and vascular parameters were recorded during the treatment schedule and follow-up as measures of treatment response. ESCC cell lines (ECA109 and TE13) and human umbilical vein endothelial cells (HUVECs) were developed to investigate the outcomes and toxicities of rh-Endo and RT in vitro. Hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were also evaluated. In vivo studies of ECA109-bearing xenografts showed that rh-Endo improved the radioresponse, with normalization of tumor vasculature and a reduction in hypoxia. In vitro studies showed that rh-Endo did not radiosensitize ESCC cell lines but did affect endothelial cells with a time- and dose-dependent manner. Studies of the molecular mechanism indicated that the improved radioresponse might be due to crosstalk between cancer cells and endothelial cells involving HIF and VEGF expression. Our data suggest that rh-Endo may be a potential anti-angiogenic agent in ESCC especially when combined with RT. The improved radioresponse arises from normalization of tumor vasculature and a reduction in hypoxia.
Universal electronic structure of polar oxide hetero-interfaces
Authors: Treske Uwe , Heming Nadine , Knupfer Martin , Büchner Bernd , Gennaro Emiliano Di , Khare Amit , Di Uccio Umberto Scotti , Granozio Fabio Miletto , Krause Stefan , Koitzsch Andreas 
Published: September 2015

AbstractThe electronic properties of NdGaO3/SrTiO3, LaGaO3/SrTiO3 and LaAlO3/SrTiO3 interfaces, all showing an insulator-to-metal transition as a function of the overlayer-thickness, are addressed in a comparative study based on x-ray absorption, x-ray photoemission and resonant photoemission spectroscopy. The nature of the charge carriers, their concentration and spatial distribution as well as the interface band alignments and the overall interface band diagrams are studied and quantitatively evaluated. The behavior of the three analyzed heterostructures is found to be remarkably similar. The valence band edge of all the three overlayers aligns to that of bulk SrTiO3. The near-interface SrTiO3 layer is affected, at increasing overlayer thickness, by the building-up of a confining potential. This potential bends both the valence and the conduction band downwards. The latter one crossing the Fermi energy in the proximity of the interface and determines the formation of an interfacial band offset growing as a function of thickness. Quite remarkably, but in agreement with previous reports for LaAlO3/SrTiO3, no electric field is detected inside any of the polar overlayers. The essential phenomenology emerging from our findings is discussed on the base of different alternative scenarios regarding the origin of interface carriers and their interaction with an intense photon beam.
Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis
Authors: Chen Guohai , Tzekov Radouil , Li Wensheng , Jiang Fangzheng , Mao Sihong , Tong Yuhua 
Published: September 2015

AbstractThe purpose of this study is to investigate whether the Y402H polymorphism (rs1061170, a T-to-C transition at amino acid position 402) in the complement factor H (CFH) gene have a pharmacogenetics effect on the anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). We performed a meta-analysis using databases including PubMed and EMBASE to find relevant studies. 13 published association studies were selected for this meta-analysis, including 2704 patients. For the CFH Y402H polymorphism, anti-VEGF treatment was much less effective in AMD patients with the CFH CC genotype (CC versus TT: odds ratio (OR) = 55, 95% confidence interval (CI), 0.31 to 0.95, P = 0.03; CC versus CT: OR = 0.60, 95% CI, 0.40 to 0.91, P = 0.02; and CC versus CT + TT: OR = 0.59, 95% CI, 0.38 to 0.90, P = 0.02, respectively). In subgroup analysis, CFH Y402H polymorphism was more likely to be a predictor of response for Caucasians (CC versus CT+TT: OR = 0.63, 95% CI, 0.42 to 0.95, P = 0.03). In conclusion, pharmacogenetics of CFH Y402H polymorphism may play a role in response to anti-VEGF treatment for neovascular AMD, especially for Caucasians.
Gender difference in advanced HIV disease and late presentation according to European consensus definitions
Authors: Jiang Hongbo , Yin Jieyun , Fan Yunzhou , Liu Jianhua , Zhang Zhixia , Liu Li , Nie Shaofa 
Published: September 2015

AbstractEffectiveness of highly active antiretroviral therapy is limited for a large proportion of individuals living with HIV presenting for medical care at an advanced stage. Controversial results of gender differences in risk of late HIV diagnosis were reported among existing literatures. Therefore, we conducted this meta-analysis to synthesize a summary of gender differences in risk of advanced HIV disease (AHD) and late presentation (LP) according to European consensus definitions. Totally, 32 studies were included based on predetermined selection criteria. The pooled adjusted odds ratios of males presenting with AHD and LP compared with females were 1.73 (95% confidence interval [CI], 1.59–1.89) and 1.38 (95% CI, 1.18–1.62) with significant heterogeneity observed (I2 = 78.50% and I2 = 85.60%, respectively). Subgroup analysis revealed that time lag, study location, number of patients, proportion of females, study design, number of adjusted variables might be potential source of heterogeneity. Sensitivity analysis showed robustness of the results. No publication bias was observed in studies on AHD or LP. The current meta-analysis indicated that males are at higher risk of AHD or LP compared with females. More attention should be paid to males to make sure early testing, diagnosis and treatment and ultimately improve individual and population health.
Competition between diagonal and off-diagonal coupling gives rise to charge-transfer states in polymeric solar cells
Authors: Yao Yao , Zhou Nengji , Prior Javier , Zhao Yang 
Published: September 2015

AbstractIt has long been a puzzle on what drives charge separation in artificial polymeric solar cells as a consensus has yet to emerge among rivaling theories based upon electronic localization and delocalization pictures. Here we propose an alternative using the two-bath spin-boson model with simultaneous diagonal and off-diagonal coupling: the critical phase, which is born out of the competition of the two coupling types and is neither localized nor delocalized. The decoherence-free feature of the critical phase also helps explain sustained coherence of the charge-transfer state. Exploiting Hamiltonian symmetries in an enhanced algorithm of density-matrix renormalization group, we map out boundaries of the critical phase to a precision previously unattainable and determine the bath spectral densities inducive to the existence of the charge-transfer state.
Structural Mechanism for Regulation of Bcl-2 protein Noxa by phosphorylation
Authors: Karim Christine B. , Michel Espinoza-Fonseca L. , James Zachary M. , Hanse Eric A. , Gaynes Jeffrey S. , Thomas David D. , Kelekar Ameeta 
Published: September 2015

AbstractWe showed previously that phosphorylation of Noxa, a 54-residue Bcl-2 protein, at serine 13 (Ser13) inhibited its ability to promote apoptosis through interactions with canonical binding partner, Mcl-1. Using EPR spectroscopy, molecular dynamics (MD) simulations and binding assays, we offer evidence that a structural alteration caused by phosphorylation partially masks Noxa’s BH3 domain, inhibiting the Noxa-Mcl-1 interaction. EPR of unphosphorylated Noxa, with spin-labeled amino acid TOAC incorporated within the BH3 domain, revealed equilibrium between ordered and dynamically disordered states. Mcl-1 further restricted the ordered component for non-phosphorylated Noxa, but left the pSer13 Noxa profile unchanged. Microsecond MD simulations indicated that the BH3 domain of unphosphorylated Noxa is housed within a flexible loop connecting two antiparallel β-sheets, flanked by disordered N- and C-termini and Ser13 phosphorylation creates a network of salt-bridges that facilitate the interaction between the N-terminus and the BH3 domain. EPR showed that a spin label inserted near the N-terminus was weakly immobilized in unphosphorylated Noxa, consistent with a solvent-exposed helix/loop, but strongly constrained in pSer13 Noxa, indicating a more ordered peptide backbone, as predicted by MD simulations. Together these studies reveal a novel mechanism by which phosphorylation of a distal serine inhibits a pro-apoptotic BH3 domain and promotes cell survival.
Reporter pathway analysis from transcriptome data: Metabolite-centric versus Reaction-centric approach
Authors: Çakır Tunahan 
Published: September 2015

AbstractA systems-based investigation of the effect of perturbations on metabolic machinery is crucial to elucidate the mechanism behind perturbations. One way to investigate the perturbation-induced changes within the cell metabolism is to focus on pathway-level effects. In this study, three different perturbation types (genetic, environmental and disease-based) are analyzed to compute a list of reporter pathways, metabolic pathways which are significantly affected from a perturbation. The most common omics data type, transcriptome, is used as an input to the bioinformatic analysis. The pathways are scored by two alternative approaches: by averaging the changes in the expression levels of the genes controlling the associated reactions (reaction-centric) and by averaging the changes in the associated metabolites which were scored based on the associated genes (metabolite-centric). The analysis reveals the superiority of the novel metabolite-centric approach over the commonly used reaction-centric approach since it is based on metabolites which better represent the cross-talk among different pathways, enabling a more global and realistic cataloguing of network-wide perturbation effects.
A generalized target theory and its applications
Authors: Zhao Lei , Mi Dong , Hu Bei , Sun Yeqing 
Published: September 2015

AbstractDifferent radiobiological models have been proposed to estimate the cell-killing effects, which are very important in radiotherapy and radiation risk assessment. However, most applied models have their own scopes of application. In this work, by generalizing the relationship between “hit” and “survival” in traditional target theory with Yager negation operator in Fuzzy mathematics, we propose a generalized target model of radiation-induced cell inactivation that takes into account both cellular repair effects and indirect effects of radiation. The simulation results of the model and the rethinking of “the number of targets in a cell” and “the number of hits per target” suggest that it is only necessary to investigate the generalized single-hit single-target (GSHST) in the present theoretical frame. Analysis shows that the GSHST model can be reduced to the linear quadratic model and multitarget model in the low-dose and high-dose regions, respectively. The fitting results show that the GSHST model agrees well with the usual experimental observations. In addition, the present model can be used to effectively predict cellular repair capacity, radiosensitivity, target size, especially the biologically effective dose for the treatment planning in clinical applications.
A peptide factor secreted by Staphylococcus pseudintermedius exhibits properties of both bacteriocins and virulence factors
Authors: Wladyka Benedykt , Piejko Marcin , Bzowska Monika , Pieta Piotr , Krzysik Monika , Mazurek Łukasz , Guevara-Lora Ibeth , Bukowski Michał , Sabat Artur J. , Friedrich Alexander W. , Bonar Emilia , Międzobrodzki Jacek , Dubin Adam , Mak Paweł 
Published: September 2015

AbstractStaphylococcus pseudintermedius is a common commensal bacterium colonizing the skin and mucosal surfaces of household animals. However, it has recently emerged as a dangerous opportunistic pathogen, comparable to S. aureus for humans. The epidemiological situation is further complicated by the increasing number of methicillin-resistant S. pseudintermedius infections and evidence of gene transmission driving antibiotic resistance between staphylococci colonizing human and zoonotic hosts. In the present study, we describe a unique peptide, BacSp222, that possesses features characteristic of both bacteriocins and virulence factors. BacSp222 is secreted in high quantities by S. pseudintermedius strain 222 isolated from dog skin lesions. This linear, fifty-amino-acid highly cationic peptide is plasmid-encoded and does not exhibit significant sequence similarities to any other known peptides or proteins. BacSp222 kills gram-positive bacteria (at doses ranging from 0.1 to several micromol/l) but also demonstrates significant cytotoxic activities towards eukaryotic cells at slightly higher concentrations. Moreover, at nanomolar concentrations, the peptide also possesses modulatory properties, efficiently enhancing interferon gamma-induced nitric oxide release in murine macrophage-like cell lines. BacSp222 appears to be one of the first examples of multifunctional peptides that breaks the convention of splitting bacteriocins and virulence factors into two unrelated groups.