bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress kinases, endoplasmic reticulum stress, and Alzheimer’s disease related markers in peripheral blood mononuclear cells from subjects with increased body weight
Authors: Lei Ting , Yu Lugang , Qin Liqiang , Xu Baohui , Zhou Lingmei , Cheng Jinbo , Zhou Hui , Pang Xing , Wan Zhongxiao 
Published: August 2016

AbstractWe aimed to characterize endoplasmic reticulum stress, inflammation, and Alzheimer’s disease (AD) related markers in peripheral blood mononuclear cells (PBMCs) from males with varied BMI; and to explore whether high glucose and fatty acids (FFAs) might be critical factors for inducing metabolic alterations in PBMCs under obese condition. Approximately 45 middle-aged men were enrolled with varied BMI. At the protein expression level, compared to the lean, the phosphorylation of AMPK, and p-Akt at serine 473 were significantly reduced from the overweight (OW) and/or obese (OB); while the protein expression of p-JNK, cleaved caspase 3, CHOP and p-eIF2α were elevated from the OW and/or OB. At the mRNA expression level, ER stress markers (i.e. GRP78, CHOP and XBP-1), inflammatory markers (i.e.TLR2, TLR4 and CCR2) and AD markers (i.e. APP, PS1 and PS2) were significantly higher in PBMCs from OB compared to lean. In cultured PBMCs, high glucose and FFAs induced GRP78, CHOP and XBP-1 mRNA, and high glucose also induced APP, PS1 and PS2 mRNA. In conclusion, altered markers including AMPK, ER stress and AD related makers under obese condition could be easily obtained from PBMCs. These markers might provide new mechanistic links between obesity and other metabolic complications including AD.
Implementation and Quality Control of Lung Cancer EGFR Genetic Testing by MALDI-TOF Mass Spectrometry in Taiwan Clinical Practice
Authors: Su Kang-Yi , Kao Jau-Tsuen , Ho Bing-Ching , Chen Hsuan-Yu , Chang Gee-Cheng , Ho Chao-Chi , Yu Sung-Liang 
Published: August 2016

AbstractMolecular diagnostics in cancer pharmacogenomics is indispensable for making targeted therapy decisions especially in lung cancer. For routine clinical practice, the flexible testing platform and implemented quality system are important for failure rate and turnaround time (TAT) reduction. We established and validated the multiplex EGFR testing by MALDI-TOF MS according to ISO15189 regulation and CLIA recommendation in Taiwan. Totally 8,147 cases from Aug-2011 to Jul-2015 were assayed and statistical characteristics were reported. The intra-run precision of EGFR mutation frequency was CV 2.15% (L858R) and 2.77% (T790M); the inter-run precision was CV 3.50% (L858R) and 2.84% (T790M). Accuracy tests by consensus reference biomaterials showed 100% consistence with datasheet (public database). Both analytical sensitivity and specificity were 100% while taking Sanger sequencing as the gold-standard method for comparison. EGFR mutation frequency of peripheral blood mononuclear cell for reference range determination was 0.002 ± 0.016% (95% CI: 0.000–0.036) (L858R) and 0.292 ± 0.289% (95% CI: 0.000–0.871) (T790M). The average TAT was 4.5 working days and the failure rate was less than 0.1%. In conclusion, this study provides a comprehensive report of lung cancer EGFR mutation detection from platform establishment, method validation to clinical routine practice. It may be a reference model for molecular diagnostics in cancer pharmacogenomics.
Specific detection of interferon regulatory factor 5 (IRF5): A case of antibody inequality
Authors: Li Dan , De Saurav , Li Dan , Song Su , Matta Bharati , Barnes Betsy J. 
Published: August 2016

AbstractInterferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors. IRF5 was first identified and characterized as a transcriptional regulator of type I interferon expression after virus infection. In addition to its critical role(s) in the regulation and development of host immunity, subsequent studies revealed important roles for IRF5 in autoimmunity, cancer, obesity, pain, cardiovascular disease and metabolism. Based on these important disease-related findings, a large number of commercial antibodies have become available to study the expression and function of IRF5. Here we validate a number of these antibodies for the detection of IRF5 by immunoblot, flow cytometry and immunofluorescence or immunohistochemistry using well-established positive and negative controls. Somewhat surprising, the majority of commercial antibodies tested were unable to specifically recognize human or mouse IRF5. We present data on antibodies that do specifically recognize human or mouse IRF5 in a particular application. These findings reiterate the importance of proper controls and molecular weight standards for the analysis of protein expression. Given that dysregulated IRF5 expression has been implicated in the pathogenesis of numerous diseases, including autoimmune and cancer, results indicate that caution should be used in the evaluation and interpretation of IRF5 expression analysis.
Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke
Authors: Vahid-Ansari F , Lagace D C , Albert P R 
Published: August 2016

AbstractPost-stroke depression (PSD) is a common outcome following stroke that is associated with poor recovery. To develop a preclinical model of PSD, we targeted a key node of the depression–anxiety circuitry by inducing a unilateral ischemic lesion to the medial prefrontal cortex (mPFC) stroke. Microinjection of male C57/BL6 mice with endothelin-1 (ET-1, 1600 pmol) induced a small (1 mm3) stroke consistently localized within the left mPFC. Compared with sham control mice, the stroke mice displayed a robust behavioral phenotype in four validated tests of anxiety including the elevated plus maze, light–dark, open-field and novelty-suppressed feeding tests. In addition, the stroke mice displayed depression-like behaviors in both the forced swim and tail suspension test. In contrast, there was no effect on locomotor activity or sensorimotor function in the horizontal ladder, or cylinder and home cage activity tests, indicating a silent stroke due to the absence of motor abnormalities. When re-tested at 6 weeks post stroke, the stroke mice retained both anxiety and depression phenotypes. Surprisingly, at 6 weeks post stroke the lesion site was infiltrated by neurons, suggesting that the ET-1-induced neuronal loss in the mPFC was reversible over time, but was insufficient to promote behavioral recovery. In summary, unilateral ischemic lesion of the mPFC results in a pronounced and persistent anxiety and depression phenotype with no evident sensorimotor deficits. This precise lesion of the depression circuitry provides a reproducible model to study adaptive cellular changes and preclinical efficacy of novel interventions to alleviate PSD symptoms.
Shakespearean allusion and the detective fiction of Georgette Heyer
Authors: Hopkins Lisa 
Published: August 2016

AbstractThis essay argues that Shakespearean allusion is a recurrent and important factor in the detective novels of Georgette Heyer. Though the master text for Heyer is Hamlet, a variety of Shakespeare plays are referred to, and mention of them functions in multiple ways. Quotations from Shakespeare reveal truths about the characters and comment on their situations and personalities. They also afford points of entry for people previously unacquainted to talk to each other, and finally they have effects in terms of genre, since their presence can, with equal facility, tend towards comic relief (in line with a tradition in golden-age crime fiction of using Macbeth in particular to comic effect) or work to add gravitas and resonance. The use of Shakespearean allusion is thus central to Heyer’s technique. This article is published as part of a collection to commemorate the 400th anniversary of William Shakespeare’s death.
The Rothschild report (1971) and the purpose of government-funded R&D—a personal account
Authors: Parker Miles 
Published: August 2016

AbstractIn 1971, (Lord) Victor Rothschild, reported to Government on “The Organisation and Management of Government R&D” and how government could become (in his words) a customer for research contracted from the Research Councils and other sources. Rothschild’s thinking implied that management of R&D by “customer” Departments would bring an understanding of research outputs. He proposed the transfer of applied science funds from Research Councils to Government Departments, providing each with a Chief Scientist as proxy customer for research to be commissioned on a “customer/contractor” basis. The Government largely adopted his proposals in 1972 and implemented them in 1974. The Rothschild reforms and the upheavals they brought were controversial at the time, though now in some instances, reversed and otherwise either forgotten or buried in unconscious assumptions. However, the Rothschild framework still underpins important assumptions about Departmental relationships with the science community, which in my view adversely affected the access of Government to expert advice. From the viewpoint of a participant in Government R&D management through this period, I explore the immediate response and the post-1980 history of the Rothschild reforms, discuss the way in which research commissioning became such a heavy task as to impede analysis and advice delivery, and consider alternative approaches, such as the “science broker” model. This article is published as part of a collection on scientific advice to governments.
High-frequency oscillations in human and monkey neocortex during the wake–sleep cycle
Authors: Le Van Quyen Michel , Muller Lyle E. , Telenczuk Bartosz , Halgren Eric , Cash Sydney , Hatsopoulos Nicholas G. , Dehghani Nima , Destexhe Alain 
Published: August 2016

Significance
We show in humans that in comparison to excitatory cells, inhibitory neurons have a stronger spiking activity during γ oscillations in the wake–sleep cycle. During β-oscillations in monkey neocortex, inhibitory cells show more active firing. Unlike excitatory cells, inhibitory cells show correlations during slow-wave sleep fast oscillations over several millimeters in the neocortex. During both wake and sleep, β- and γ-waves systematically propagate with a dominant trajectory across the array with similar velocities. These findings suggest that inhibition-driven β- and γ-oscillations may contribute to the reactivation of information during sleep through orchestrating highly coherent spiking activity patterns.
Classification of topological phonons in linear mechanical metamaterials
Authors: Süsstrunk Roman , Huber Sebastian D. 
Published: August 2016

Significance
A mechanical metamaterial is an engineered material that is characterized by properties that go beyond the properties of its microscopic building blocks. Specifically, in topological metamaterials, one makes use of surface or boundary modes that are stable against imperfections or environmental influences and hence constitute reliable building blocks for various applications. In our work, we provide a classification scheme of possible topological metamaterials and an extensive number of examples illustrating this scheme. Our classification can serve as an important blueprint for many future applications that target such stable boundary modes for engineering purposes.
Charge-induced nematicity in FeSe
Authors: Massat Pierre , Farina Donato , Paul Indranil , Karlsson Sandra , Strobel Pierre , Toulemonde Pierre , Méasson Marie-Aude , Cazayous Maximilien , Sacuto Alain , Kasahara Shigeru , Shibauchi Takasada , Matsuda Yuji , Gallais Yann 
Published: August 2016

Significance
Anisotropic electron liquids are ubiquitous in many correlated electron systems. Among them, electron nematics, which break rotation but not translation symmetry, are believed to play a key role in the physics of both cuprates and iron-based superconductors (Fe SC). However the study of electron nematicity has been hampered by the lack of an adequate probe of its associated fluctuations and susceptibility, making it difficult to track its origin. Here, using polarization-resolved Raman scattering, we report the detection of critical nematic fluctuations in the charge channel in the Fe SC compound FeSe. The strong enhancement of the associated nematic susceptibility allows us to link the appearance of nematicity to a symmetry-breaking distortion of the Fermi surface.
Distinct cellular properties of oncogenic KIT receptor tyrosine kinase mutants enable alternative courses of cancer cell inhibition
Authors: Shi Xiarong , Sousa Leiliane P. , Mandel-Bausch Elizabeth M. , Tome Francisco , Reshetnyak Andrey V. , Hadari Yaron , Schlessinger Joseph , Lax Irit 
Published: August 2016

Significance
A common practice in modern clinics is to identify a match between a mutated oncogenic protein that functions as a “driver” of a particular cancer with a known or new cancer drug from available targeted therapies. To understand mechanisms underlying the differential clinical impact of various targeted therapies on cancers driven by the receptor tyrosine kinase KIT, we analyzed a variety of biochemical and cellular properties of the most common KIT somatic mutations identified in human cancers. Surprisingly, each of the six major KIT oncogenic mutants exhibits distinct properties and responds differently to targeted therapies. These experiments show that detailed biochemical and cellular analyses of oncogenic mutations are required to optimize precision medicine for cancer treatment.
Which bulges are favoured by barred S0 galaxies?
Authors: Barway Sudhanshu , Saha Kanak , Vaghmare Kaustubh , Kembhavi Ajit K. 
Published: August 2016

Abstract
S0 galaxies are known to host classical bulges with a broad range of size and mass, while some such S0s are barred and some not. The origin of the bars has remained a long-standing problem – what made bar formation possible in certain S0s? By analysing a large sample of S0s with classical bulges observed by the Spitzer Space Telescope, we find that most of our barred S0s host comparatively low-mass classical bulges, typically with bulge-to-total ratio less than 0.5, whereas S0s with more massive classical bulges than these do not host any bar. Furthermore, we find that amongst the barred S0s, there is a trend for the longer and massive bars to be associated with comparatively bigger and massive classical bulges – possibly suggesting bar growth being facilitated by these classical bulges. In addition, we find that the bulge effective radius is always less than the bar effective radius – indicating an interesting synergy between the host classical bulge and bars being maintained while bar growth occurred in these S0s.
Near-infrared spectroscopy of faint discrete X-ray point sources constituting the Galactic ridge X-ray emission
Authors: Morihana Kumiko , Tsujimoto Masahiro , Dubath Pierre , Yoshida Tessei , Suzuki Kensuke , Ebisawa Ken 
Published: August 2016

Abstract
The Galactic Ridge X-ray Emission (GRXE) is an apparently extended X-ray emission along the Galactic plane. The X-ray spectrum is characterized by a hard continuum with a strong Fe K emission feature in the 6–7 keV band. A substantial fraction (∼80%) of the GRXE in the Fe band was resolved into point sources by deep Chandra imaging observations; thus GRXE is mostly composed of dim Galactic X-ray point sources, at least in this energy band. To investigate the populations of these dim X-ray point sources, we carried out near-infrared (NIR) follow-up spectroscopic observations in two deep Chandra fields located in the Galactic plane at (l, b) = (0 $_{.}^{\circ}$1, −1 $_{.}^{\circ}$4) and (28 $_{.}^{\circ}$5, 0 $_{.}^{\circ}$0) using NTT/SofI and Subaru/MOIRCS. We obtained well-exposed NIR spectra from 65 objects and found that there are three main classes of Galactic sources based on the X-ray color and NIR spectral features: those having (A) hard X-ray spectra and NIR emission features such as H i (Brγ), He i, and He ii (2 objects), (B) soft X-ray spectra and NIR absorption features such as H i, Na i, Ca i, and CO (46 objects), and (C) hard X-ray spectra and NIR absorption features such as H i, Na i, Ca i, and CO (17 objects). From these features, we argue that class A sources are cataclysmic variables (CVs), and class B sources are late-type stars with enhanced coronal activity, which is in agreement with current knowledge. Class C sources possibly belong to a new group of objects, which has been poorly studied so far. We argue that the candidate sources for class C are the binary systems hosting white dwarfs and late-type companions with very low accretion rates. It is likely that this newly recognized class of sources contribute to a non-negligible fraction of the GRXE, especially in the Fe K band.
Superoutburst of CR Bootis: Estimation of mass ratio of a typical AM CVn star by stage A superhumps
Authors: Isogai Keisuke , Kato Taichi , Ohshima Tomohito , Kasai Kiyoshi , Oksanen Arto , Masumoto Kazunari , Fukushima Daiki , Maeda Kazuki , Kawabata Miho , Matsuda Risa , Kojiguchi Naoto , Sugiura Yuki , Takeda Nao , Matsumoto Katsura , Itoh Hiroshi , Pavlenko Elena P. , Antonyuk Kirill , Antonyuk Oksana , Pit Nikolai , Sosnovskij Aleksei , Baklanov Alex , Babina Julia , Sklyanov Aleksandr , Kiyota Seiichiro , Hambsch Franz-Josef , Littlefield Colin , Maeda Yutaka , Cook Lewis M. , Masi Gianluca , Dubovsky Pavol A. , Novák Rudolf , Dvorak Shawn , Imada Akira , Nogami Daisaku 
Published: August 2016

AbstractWe report on two superoutbursts of the AM CVn-type object CR Boo in 2014 April–March and 2015 May–June. A precursor outburst accompanied both of these superoutbursts. During the rising branch of the main superoutburst in 2014, we detected growing superhumps (stage A superhumps) whose period was 0.017669(24) d. Assuming that this period reflects the dynamical precession rate at the radius of the 3:1 resonance, we could estimate the mass ratio (q = M2/M1) of 0.101(4) by using the stage A superhump period and the orbital period of 0.0170290(6) d. This mass ratio is consistent with that expected from the theoretical evolutionary model of AM CVn-type objects. The detection of precursor outbursts and stage A superhumps is the second case in AM CVn-type objects. There are two interpretations of the outbursts of AM CVn-type objects. One is a dwarf nova (DN) outbursts analogy, which suggets that the outbursts are caused by thermal and tidal instabilities. Another is the VY Scl-type variation, which suggests that the outbursts are caused by the variation of the mass-transfer rate of the secondary.This detection of the superhump variations strongly supports the former interpretation.
Telling plant species apart with DNA: from barcodes to genomes
Authors: Hollingsworth Peter M. , Li De-Zhu , van der Bank Michelle , Twyford Alex D. 
Published: August 2016

Land plants underpin a multitude of ecosystem functions, support human livelihoods and represent a critically important component of terrestrial biodiversity—yet many tens of thousands of species await discovery, and plant identification remains a substantial challenge, especially where material is juvenile, fragmented or processed. In this opinion article, we tackle two main topics. Firstly, we provide a short summary of the strengths and limitations of plant DNA barcoding for addressing these issues. Secondly, we discuss options for enhancing current plant barcodes, focusing on increasing discriminatory power via either gene capture of nuclear markers or genome skimming. The former has the advantage of establishing a defined set of target loci maximizing efficiency of sequencing effort, data storage and analysis. The challenge is developing a probe set for large numbers of nuclear markers that works over sufficient phylogenetic breadth. Genome skimming has the advantage of using existing protocols and being backward compatible with existing barcodes; and the depth of sequence coverage can be increased as sequencing costs fall. Its non-targeted nature does, however, present a major informatics challenge for upscaling to large sample sets.This article is part of the themed issue ‘From DNA barcodes to biomes’.
PathScore: a web tool for identifying altered pathways in cancer data
Authors: Gaffney Stephen G. , Townsend Jeffrey P. 
Published: August 2016

ABSTRACTSummaryPathScorequantifies the level of enrichment of somatic mutations within curated pathways, applying a novel approach that identifies pathways enriched across patients. The application provides several user-friendly, interactive graphic interfaces for data exploration, including tools for comparing pathway effect sizes, significance, gene-set overlap and enrichment differences between projects.Availability and ImplementationWeb application available atpathscore.publichealth.yale.edu. Site implemented in Python and MySQL, with all major browsers supported. Source code available at github.com/sggaffney/pathscore with a GPLv3 license.Contactstephen.gaffney@yale.eduSupplementary InformationAdditional documentation can be found athttp://pathscore.publichealth.yale.edu/faq.
Evolutionary thrift: mycobacteria repurpose plasmid diversity during adaptation of type VII secretion systems
Authors: Mortimer Tatum D. , Weber Alexandra M. , Pepperell Caitlin S. 
Published: August 2016

AbstractMycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS. Plasmid-borne ESX were described recently, and we found evidence that the initial duplication and divergence of ESX systems occurred on plasmids and was driven by selection for advantageous mutations. Plasmid conjugation has been linked to T7SS and type IV secretion systems (T4SS) in mycobacteria, and we discovered that T7SS and T4SS genes evolved in concert on the plasmids. We hypothesize that differentiation of plasmid ESX helps to prevent conjugation among cells harboring incompatible plasmids. Plasmid ESX appear to have been repurposed following migration to the chromosome, and there is evidence of positive selection driving further differentiation of chromosomal ESX. We hypothesize that ESX loci were initially stabilized on the chromosome by mediating their own transfer. These results emphasize the diverse adaptive paths underlying evolution of novelty, which in this case involved plasmid duplications, selection for advantageous mutations in the mobile and core genomes, migration of the loci between plasmids and chromosomes, and lateral transfer among chromosomes. We discuss further implications for the choice of model organism to study ESX functions inMycobacterium tuberculosis.