bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine
Authors: Theiler James , Yoon Hyejin , Yusim Karina , Picker Louis J. , Fruh Klaus , Korber Bette 
Published: October 2016

AbstractEpigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Epigraph vaccine antigens are functionally similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster and in restricted cases, provides a mathematically optimal solution. Epigraph furthermore has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches and to apply the code to both aligned and unaligned input sequences. Epigraph was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).
Silver Nanowire-IZO-Conducting Polymer Hybrids for Flexible and Transparent Conductive Electrodes for Organic Light-Emitting Diodes
Authors: Yun Ho Jun , Kim Se Jung , Hwang Ju Hyun , Shim Yong Sub , Jung Sun-Gyu , Park Young Wook , Ju Byeong-Kwon 
Published: October 2016

AbstractSolution-processed silver nanowire (AgNW) has been considered as a promising material for next-generation flexible transparent conductive electrodes. However, despite the advantages of AgNWs, some of their intrinsic drawbacks, such as large surface roughness and poor interconnection between wires, limit their practical application in organic light-emitting diodes (OLEDs). Herein, we report a high-performance AgNW-based hybrid electrode composed of indium-doped zinc oxide (IZO) and poly (3,4-ethylenediowythiophene):poly(styrenesulfonate) [PEDOT:PSS]. The IZO layer protects the underlying AgNWs from oxidation and corrosion and tightly fuses the wires together and to the substrate. The PEDOT:PSS effectively reduces surface roughness and increases the hybrid films’ transmittance. The fabricated electrodes exhibited a low sheet resistance of 5.9 Ωsq−1 with high transmittance of 86% at 550 nm. The optical, electrical, and mechanical properties of the AgNW-based hybrid films were investigated in detail to determine the structure-property relations, and whether optical or electrical properties could be controlled with variation in each layer’s thickness to satisfy different requirements for different applications. Flexible OLEDs (f-OLEDs) were successfully fabricated on the hybrid electrodes to prove their applicability; their performance was even better than those on commercial indium doped tin oxide (ITO) electrodes.
Extracting quantitative information from single-molecule super-resolution imaging data with LAMA – LocAlization Microscopy Analyzer
Authors: Malkusch Sebastian , Heilemann Mike 
Published: October 2016

AbstractSuper-resolution fluorescence microscopy revolutionizes cell biology research and provides novel insights on how proteins are organized at the nanoscale and in the cellular context. In order to extract a maximum of information, specialized tools for image analysis are necessary. Here, we introduce the LocAlization Microscopy Analyzer (LAMA), a comprehensive software tool that extracts quantitative information from single-molecule super-resolution imaging data. LAMA allows characterizing cellular structures by their size, shape, intensity, distribution, as well as the degree of colocalization with other structures. LAMA is freely available, platform-independent and designed to provide direct access to individual analysis of super-resolution data.
Rhein reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal fibrosis in mice
Authors: Zhang Qin , Yin Shasha , Liu Lin , Liu Zhihong , Cao Wangsen 
Published: October 2016

AbstractRenal fibrosis is the hallmark of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications. Rhein, a plant-derived anthraquinone, displays strong anti-fibrosis properties, but its protective mode of action remains incompletely understood. Here we explore the mechanism of Rhein anti-renal fibrosis by investigating its regulation of Klotho, a known renal anti-fibrotic protein whose suppression after renal injury reportedly involves aberrant DNA methylation. We report that Rhein is an impressive up-regulator of Klotho and it markedly reversed Klotho down-regulation in unilateral ureteral occlusion-induced fibrotic kidney. Further examinations revealed that Klotho loss in fibrotic kidney is associated with Klotho promoter hypermethylation due to aberrant methyltransferase 1 and 3a expressions. However, Rhein significantly corrected all these epigenetic alterations and subsequently alleviated pro-fibrotic protein expression and renal fibrosis, whereas Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Rhein, suggesting that Rhein epigenetic reversal of Klotho loss represents a critical mode of action that confers Rhein’s anti- renal fibrotic functions. Altogether our studies uncover a novel hypomethylating character of Rhein in preventing Klotho loss and renal fibrosis, and demonstrate the efficacy of Klotho-targeted epigenetic intervention in potential treatment of renal fibrosis-associated kidney diseases.
Dietary resources shape the adaptive changes of cyanide detoxification function in giant panda (Ailuropoda melanoleuca)
Authors: Huang He , Yie Shangmian , Liu Yuliang , Wang Chengdong , Cai Zhigang , Zhang Wenping , Lan Jingchao , Huang Xiangming , Luo Li , Cai Kailai , Hou Rong , Zhang Zhihe 
Published: October 2016

AbstractThe functional adaptive changes in cyanide detoxification in giant panda appear to be response to dietary transition from typical carnivore to herbivorous bear. We tested the absorption of cyanide contained in bamboo/bamboo shoots with a feeding trial in 20 adult giant pandas. We determined total cyanide content in bamboo shoots and giant panda’s feces, levels of urinary thiocyanate and tissue rhodanese activity using color reactions with a spectrophotometer. Rhodanese expression in liver and kidney at transcription and translation levels were measured using real-time RT-PCR and immunohistochemistry, respectively. We compared differences of rhodanese activity and gene expressions among giant panda, rabbit (herbivore) and cat (carnivore), and between newborn and adult giant pandas. Bamboo shoots contained 3.2 mg/kg of cyanide and giant pandas absorbed more than 65% of cyanide. However, approximately 80% of absorbed cyanide was metabolized to less toxic thiocyanate that was discharged in urine. Rhodanese expression and activity in liver and kidney of giant panda were significantly higher than in cat, but lower than in rabbit (all P < 0.05). Levels in adult pandas were higher than that in newborn cub. Phylogenetic analysis of both nucleotide and amino acid sequences of the rhodanese gene supported a closer relationship of giant panda with carnivores than with herbivores.
Effects of histone acetylation on superoxide dismutase 1 gene expression in the pathogenesis of senile cataract
Authors: Rong Xianfang , Qiu Xiaodi , Jiang Yongxiang , Li Dan , Xu Jie , Zhang Yinglei , Lu Yi 
Published: October 2016

AbstractHistone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types—nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)—using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly. Both H3 and H4 were deacetylated at −600 bp of the SOD1 promoter of cataract lenses, and hypoacetylated at −1500, −1200, and −900 bp. In hypoacetylated histones, the hypoacetylation pattern differed among the cataracts. In vitro, anacardic acid (AA) significantly reduced H3 and H4 acetylation at the SOD1 promoter, decreased protein expression, and induced cataract formation in rabbits. AA also inhibited HLEC viability and increased cell apoptosis. In contrast, trichostatin A (TSA) was able to efficaciously stop AA’s effects on both rabbit lenses and HLECs. Decreased histone acetylation at the SOD1 promoter is associated with declined SOD1 expression in senile cataracts. Histone acetylation plays an essential role in the regulation of SOD1 expression and in the pathogenesis of senile cataracts.
Pioglitazone Ameliorates Smooth Muscle Cell Proliferation in Cuff-Induced Neointimal Formation by Both Adiponectin-Dependent and -Independent Pathways
Authors: Kubota Tetsuya , Kubota Naoto , Sato Hiroyuki , Inoue Mariko , Kumagai Hiroki , Iwamura Tomokatsu , Takamoto Iseki , Kobayashi Tsuneo , Moroi Masao , Terauchi Yasuo , Tobe Kazuyuki , Ueki Kohjiro , Kadowaki Takashi 
Published: October 2016

AbstractThe aim of this study is to elucidate to what degree adiponectin is involved in TZD-mediated amelioration of neointimal formation. We investigated the effect of 3- or 8-weeks’ pioglitazone on cuff-induced neointimal formation in adiponectin-deficient (APN-KO) and wild-type (WT) mice. Pioglitazone for 3 weeks reduced neointimal formation in the WT mice with upregulation of the plasma adiponectin levels, but failed to reduce neointimal formation in the APN-KO mice, suggesting that pioglitazone suppressed neointimal formation by adiponectin-dependent mechanisms. Pioglitazone for 3 weeks suppressed vascular smooth muscle cell (VSMC) proliferation and increased AdipoR2 expression in the WT mice. In vitro, globular adiponectin activated AMPK through both AdipoR1 and AdipoR2, resulting in the inhibition of VSMC proliferation. Interestingly, 8-weeks’ pioglitazone was reduced neointimal formation in APN-KO mice to degree similar to that seen in the WT mice, suggesting that pioglitazone can also suppress neointimal formation via a mechanism independent of adiponectin. Pioglitazone for 8 weeks completely abrogated the increased VSMC proliferation, along with a reduction of cyclin B1 and cyclin D1 expressions and cardiovascular risk profile in the APN-KO mice. In vitro, pioglitazone suppressed these expressions, leading to inhibition of VSMC proliferation. Pioglitazone suppresses neointimal formation via both adiponectin-dependent and adiponectin-independent mechanisms.
Bone marrow mesenchymal stem cells attenuate 2,5-hexanedione-induced neuronal apoptosis through a NGF/AKT-dependent pathway
Authors: Wang Qingshan , Sun Guohua , Gao Chenxue , Feng Lina , Zhang Yan , Hao Jie , Zuo Enjun , Zhang Cong , Li Shuangyue , Piao Fengyuan 
Published: October 2016

AbstractGrowing evidence suggests that the increased neuronal apoptosis is involved inn-hexane-induced neuropathy. We have recently reported that bone marrow-mesenchymal stem cells-derived conditioned medium (BMSC-CM) attenuated 2,5-hexanedione (HD, the active metabolite ofn-hexane)-induced apoptosis in PC12 cells. Here, we explored the anti-apoptotic efficacy of BMSCin vivo. HD-treated rats received BMSC by tail vein injection 5 weeks after HD intoxication. We found that in grafted rats, BMSC significantly attenuated HD-induced neuronal apoptosis in the spinal cord, which was associated with elevation of nerve growth factor (NGF). Neutralization of NGF in BMSC-CM blocked the protection against HD-induced apoptosis in VSC4.1 cells, suggesting that NGF is essential for BMSC-afforded anti-apoptosis. Mechanistically, we found that the decreased activation of Akt induced by HD was significantly recovered in the spinal cord by BMSC and in VSC4.1 cells by BMSC-CM in a TrkA-dependent manner, leading to dissociation of Bad/Bcl-xL complex in mitochondria and release of anti-apoptotic Bcl-xL. The importance of Akt was further corroborated by showing the reduced anti-apoptotic potency of BMSC in HD-intoxicated VSC4.1 cells in the presence of Akt inhibitor, MK-2206. Thus, our findings show that BMSC attenuated HD-induced neuronal apoptosisin vivothrough a NGF/Akt-dependent manner, providing a novel solution againstn-hexane-induced neurotoxicity.
A novel exopolysaccharide elicitor from endophytic fungus Gilmaniella sp. AL12 on volatile oils accumulation in Atractylodes lancea
Authors: Chen Fei , Ren Cheng-Gang , Zhou Tong , Wei Yu-Jia , Dai Chuan-Chao 
Published: October 2016

AbstractEndophytes and plants can establish specific long-term symbiosis through the accumulation of secondary metabolites. Previous studies have shown that the endophytic fungus Gilmaniella sp. AL12 can stimulate Atractylodes lancea to produce volatile oils. The purpose of this report is to investigate key factors involved in the stimulation of A. lancea by AL12 and reveal the mechanism. We identified the active component from AL12 as an extracellular mannan with a polymerization degree of 26–42. Differential membrane proteomics of A. lancea was performed by 2D electrophoresis. The results showed that there were significant differences in the expression of 83 proteins. Based on these results, we conclude that AL12 secreted mannan contributes to the antagonistic balance seen in interactions between AL12 and A. lancea. One portion of the mannan was degraded to mannose for hexokinase activation, promoting photosynthesis and energy metabolism, with a potential metabolic fluxes flowing towards terpenoid biosynthesis. The other portion of the mannan directly enhanced autoimmunity of A. lancea through G protein-mediated signal transduction and the mannan-binding lectin pathway. Volatile oil accumulation was ultimately promoted in subsequent defense reactions. This study provides a new perspective on the regulation of secondary metabolites by endophytic fungal elicitors in medicinal plants.
Erosion protection conferred by whole human saliva, dialysed saliva, and artificial saliva
Authors: Baumann T. , Kozik J. , Lussi A. , Carvalho T. S. 
Published: October 2016

AbstractDuring dental erosion, tooth minerals are dissolved, leading to a softening of the surface and consequently to irreversible surface loss. Components from human saliva form a pellicle on the tooth surface, providing some protection against erosion. To assess the effect of different components and compositions of saliva on the protective potential of the pellicle against enamel erosion, we prepared four different kinds of saliva: human whole stimulated saliva (HS), artificial saliva containing only ions (AS), human saliva dialysed against artificial saliva, containing salivary proteins and ions (HS/AS), and human saliva dialysed against deionised water, containing only salivary proteins but no ions (HS/DW). Enamel specimens underwent four cycles of immersion in either HS, AS, HS/AS, HS/DW, or a humid chamber (Ctrl), followed by erosion with citric acid. During the cycling process, the surface hardness and the calcium released from the surface of the specimens were measured. The different kinds of saliva provided different levels of protection, HS/DW exhibiting significantly better protection than all the other groups (p < 0.0001). Different components of saliva, therefore, have different effects on the protective properties of the pellicle and the right proportions of these components in saliva are critical for the ability to form a protective pellicle.
The Prognostic Value of PLR in Lung Cancer, a Meta-analysis Based on Results from a Large Consecutive Cohort
Authors: Ding Nan , Pang ZhaoFei , Shen Hongchang , Ni Yang , Du Jiajun , Liu Qi 
Published: October 2016

AbstractRecently, many studies have been conducted to explore prognostic value of platelet to lymphocyte ratio (PLR) for patients with lung cancer, while the results remain controversial. We collected pretreatment, clinicopathological and follow-up data of 1388 lung cancer patients receiving surgery between 2006 and 2011 in our hospital, and reviewed relevant articles from Embase, Pubmed, Web of science databases, then performed a meta-analysis to clarify the relationship between PLR and prognosis of lung cancer patients. Finally, 11 articles with our study were included, results indicated elevated PLR was negatively related to overall survival (HR = 1.33, 95% CI: 1.10–1.62), but not related to progress-free survival (HR = 1.21, 95% CI: 0.97–1.49). Subgroup analysis suggested high PLR was correlated with poor survival in non-small cell lung cancer (HR = 1.43, 95% CI: 1.14–1.78), but not in small cell lung cancer (HR = 1.10, 95% CI: 0.76–1.58). Besides, for patients treated by chemotherapy or radiotherapy (HR = 1.66, 95% CI: 1.15–2.38) and patients in late stage (HR = 1.41, 95% CI: 1.19–1.68), PLR had significantly prognostic value. Additionally, the result was significant for patients when cut-off value of PLR was between 150 and 200 (HR = 1.47, 95% CI: 1.18–1.82). In Conclusion, this meta-analysis revealed that elevated PLR was associated with poor prognosis in lung cancer.
Deep sequencing of 10,000 human genomes
Authors: Telenti Amalio , Pierce Levi C. T. , Biggs William H. , di Iulio Julia , Wong Emily H. M. , Fabani Martin M. , Kirkness Ewen F. , Moustafa Ahmed , Shah Naisha , Xie Chao , Brewerton Suzanne C. , Bulsara Nadeem , Garner Chad , Metzker Gary , Sandoval Efren , Perkins Brad A. , Och Franz J. , Turpaz Yaron , Venter J. Craig 
Published: October 2016

Significance
Large-scale initiatives toward personalized medicine are driving a massive expansion in the number of human genomes being sequenced. Therefore, there is an urgent need to define quality standards for clinical use. This includes deep coverage and sequencing accuracy of an individual’s genome. Our work represents the largest effort to date in sequencing human genomes at deep coverage with these new standards. This study identifies over 150 million human variants, a majority of them rare and unknown. Moreover, these data identify sites in the genome that are highly intolerant to variation—possibly essential for life or health. We conclude that high-coverage genome sequencing provides accurate detail on human variation for discovery and clinical applications.
Estimating stellar wind parameters from low-resolution magnetograms
Authors: Jardine M. , Vidotto A. A. , See V. 
Published: October 2016

Abstract
Stellar winds govern the angular momentum evolution of solar-like stars throughout their main-sequence lifetime. The efficiency of this process depends on the geometry of the star's magnetic field. There has been a rapid increase recently in the number of stars for which this geometry can be determined through spectropolarimetry. We present a computationally efficient method to determine the 3D geometry of the stellar wind and to estimate the mass-loss rate and angular momentum loss rate based on these observations. Using solar magnetograms as examples, we quantify the extent to which the values obtained are affected by the limited spatial resolution of stellar observations. We find that for a typical stellar surface resolution of 20o–30o, predicted wind speeds are within 5 per cent of the value at full resolution. Mass-loss rates and angular momentum loss rates are within 5–20 per cent. In contrast, the predicted X-ray emission measures can be underestimated by one-to-two orders of magnitude, and their rotational modulations by 10–20 per cent.
Isoflurane Anesthesia Has Long-term Consequences on Motor and Behavioral Development in Infant Rhesus Macaques
Authors: Coleman Kristine , Robertson Nicola D. , Dissen Gregory A. , Neuringer Martha D. , Martin L. Drew , Cuzon Carlson Verginia C. , Kroenke Christopher , Fair Damien , Brambrink Ansgar M. 
Published: October 2016

Abstract

Background
Experimental evidence correlates anesthetic exposure during early development with neuronal and glial injury and death, as well as behavioral and cognitive impairments, in young animals. Several, although not all, retrospective human studies of neurocognitive and behavioral disorders after childhood exposure to anesthesia suggest a similar association. Few studies have specifically investigated the effects of infant anesthesia exposure on subsequent neurobehavioral development. Using a highly translational nonhuman primate model, the authors investigated the potential dose-dependent effects of anesthesia across the first year of development.

Methods
The authors examined the effects of single or multiple early postnatal isoflurane exposures on subsequent behavioral development in 24 socially reared rhesus macaques. Infants were exposed to 5 h of isoflurane anesthesia once, three times (ISO-3), or not at all (control). The authors assessed reflex development and anxiety using standardized tests. At approximately 1 yr, infants (n = 23) were weaned and housed indoors with 5 to 6 other subjects. The authors recorded their response to this move and reassessed anxiety.

Results
Compared to controls, animals exposed to repeated isoflurane (ISO-3) presented with motor reflex deficits at 1 month (median [range]: ISO-3 = 2 [1 to 5] vs. control = 5 [3 to 7]; P < 0.005) and responded to their new social environment with increased anxiety (median [range]: ISO-3 = 0.4 bouts/min [0.2 to 0.6]; control = 0.25 bouts/min [0.1 to 0.3]; P = 0.05) and affiliative/appeasement behavior (median [range]: ISO-3 = 0.1 [0 to 0.2]; control = 0 bouts/min [0 to 0.1]; P < 0.01) at 12 months. There were no statistically significant behavioral alterations after single isoflurane exposure.

Conclusions
Neonatal exposure to isoflurane, particularly when repeated, has long-term behavioral consequences affecting both motor and socioemotional aspects of behavior.
The role of epigenetics in osteoarthritis: current perspective
Authors: Ramos Yolande F.M. , Meulenbelt Ingrid 
Published: October 2016

Purpose of review
The purpose of this review is to provide an update of recent advances in the established role of different layers of epigenetic control mechanism that are used by joint cells to ensure tissue homeostasis and cope with changing microenvironment (e.g. ageing or disease).

Recent findings
New studies have further strengthened the evidence that joint tissue cells highly dependent on epigenetic control mechanisms, such as methylation at CpG-sites, noncoding RNAs and histone modifications to assure phenotypic plasticity and respective tissue homeostasis. Advancements towards high-dimensional molecular profiles and functional follow-up studies have started to uncover the complexity of these interacting networks of control. These studies highlight that in time loosening of epigenetic control increase the propensity of joint tissues to engage an osteoarthritis disease phenotype.

Summary
Identification of changes in epigenetically regulated control mechanisms in joint tissues has provided novel insight into underlying mechanism of ongoing osteoarthritis disease pathophysiology. Such insight is crucial to enable development of evidence-based therapeutic options.