bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic synaptic insulin resistance after traumatic brain injury abolishes insulin protection from amyloid beta and tau oligomer-induced synaptic dysfunction
Authors: Franklin Whitney , Krishnan Balaji , Taglialatela Giulio 
Published: June 2019

AbstractTraumatic brain injury (TBI) is a risk factor for Alzheimer’s disease (AD), although the mechanisms contributing to this increased risk are unknown. Insulin resistance is an additional risk factor for AD whereby decreased insulin signaling increases synaptic sensitivity to amyloid beta (Aβ) and tau. Considering this, we used rats that underwent a lateral fluid percussion injury at acute and chronic time-points to investigate whether decreased insulin responsiveness in TBI animals is playing a role in synaptic vulnerability to AD pathology. We detected acute and chronic decreases in insulin responsiveness in isolated hippocampal synaptosomes after TBI. In addition to assessing both Aβ and tau binding on synaptosomes, we performed electrophysiology to assess the dysfunctional impact of Aβ and tau oligomers as well as the protective effect of insulin. While we saw no difference in binding or degree of LTP inhibition by either Aβ or tau oligomers between sham and TBI animals, we found that insulin treatment was able to block oligomer-induced LTP inhibition in sham but not in TBI animals. Since insulin treatment has been discussed as a therapy for AD, this gives valuable insight into therapeutic implications of treating AD patients based on one’s history of associated risk factors.
Transcriptomic analysis of resistant and susceptible banana corms in response to infection by Fusarium oxysporum f. sp. cubense tropical race 4
Authors: Zhang Lei , Cenci Alberto , Rouard Mathieu , Zhang Dong , Wang Yunyue , Tang Weihua , Zheng Si-Jun 
Published: June 2019

AbstractFusarium wilt disease, caused by Fusarium oxysporum f. sp. cubense, especially by tropical race 4 (Foc TR4), is threatening the global banana industry. Musa acuminata Pahang, a wild diploid banana that displays strong resistance to Foc TR4, holds great potential to understand the underlying resistance mechanisms. Microscopic examination reports that, in a wounding inoculation system, the Foc TR4 infection processes in roots of Pahang (resistant) and a triploid cultivar Brazilian (susceptible) were similar by 7 days post inoculation (dpi), but significant differences were observed in corms of both genotypes at 14 dpi. We compare transcriptomic responses in the corms of Pahang and Brazilian, and show that Pahang exhibited constitutive defense responses before Foc TR4 infection and inducible defense responses prior to Brazilian at the initial Foc TR4 infection stage. Most key enzymatic genes in the phenylalanine metabolism pathway were up-regulated in Brazilian, suggesting that lignin and phytotoxin may be triggered during later stages of Foc TR4 infection. This study unravels a few potential resistance candidate genes whose expression patterns were assessed by RT-qPCR assay and improves our understanding the defense mechanisms of Pahang response to Foc TR4.
Genome-Wide DNA from Degraded Petrous Bones and the Assessment of Sex and Probable Geographic Origins of Forensic Cases
Authors: Gaudio Daniel , Fernandes Daniel M. , Schmidt Ryan , Cheronet Olivia , Mazzarelli Debora , Mattia Mirko , O’Keeffe Tadhg , Feeney Robin N. M. , Cattaneo Cristina , Pinhasi Ron 
Published: June 2019

AbstractThe acquisition of biological information and assessment of the most probable geographic origin of unidentified individuals for obtaining positive identification is central in forensic sciences. Identification based on forensic DNA, however, varies greatly in relation to degradation of DNA. Our primary aim is to assess the applicability of a petrous bone sampling method in combination with Next Generation Sequencing to evaluate the quality and quantity of DNA in taphonomically degraded petrous bones from forensic and cemetery cases. A related aim is to analyse the genomic data to obtain the molecular sex of each individual, and their most probable geographic origin. Six of seven subjects were previously identified and used for comparison with the results. To analyse their probable geographic origin, samples were genotyped for the 627.719 SNP positions. Results show that the inner ear cochlear region of the petrous bone provides good percentages of endogenous DNA (14.61–66.89%), even in the case of burnt bodies. All comparisons between forensic records and genetic results agree (sex) and are compatible (geographic origin). The application of the proposed methodology may be a powerful tool for use in forensic scenarios, ranging from missing persons to unidentified migrants who perish when crossing borders.
Automated detection of the HER2 gene amplification status in Fluorescence in situ hybridization images for the diagnostics of cancer tissues
Authors: Zakrzewski Falk , de Back Walter , Weigert Martin , Wenke Torsten , Zeugner Silke , Mantey Robert , Sperling Christian , Friedrich Katrin , Roeder Ingo , Aust Daniela , Baretton Gustavo , Hönscheid Pia 
Published: June 2019

AbstractThe human epidermal growth factor receptor 2 (HER2) gene amplification status is a crucial marker for evaluating clinical therapies of breast or gastric cancer. We propose a deep learning-based pipeline for the detection, localization and classification of interphase nuclei depending on their HER2 gene amplification state in Fluorescence in situ hybridization (FISH) images. Our pipeline combines two RetinaNet-based object localization networks which are trained (1) to detect and classify interphase nuclei into distinct classes normal, low-grade and high-grade and (2) to detect and classify FISH signals into distinct classes HER2 or centromere of chromosome 17 (CEN17). By independently classifying each nucleus twice, the two-step pipeline provides both robustness and interpretability for the automated detection of the HER2 amplification status. The accuracy of our deep learning-based pipeline is on par with that of three pathologists and a set of 57 validation images containing several hundreds of nuclei are accurately classified. The automatic pipeline is a first step towards assisting pathologists in evaluating the HER2 status of tumors using FISH images, for analyzing FISH images in retrospective studies, and for optimizing the documentation of each tumor sample by automatically annotating and reporting of the HER2 gene amplification specificities.
First report of community dynamics of arbuscular mycorrhizal fungi in radiocesium degradation lands after the Fukushima-Daiichi Nuclear disaster in Japan
Authors: Higo Masao , Kang Dong-Jin , Isobe Katsunori 
Published: June 2019

AbstractArbuscular mycorrhizal fungi (AMF) can be beneficial for improving restoration of radioactive-cesium (137Cs)-contaminated soils through soil remediation. However, there has been no information on species diversity and the composition of AMF communities in137Cs-contaminated soil after the Fukushima-Daiichi Nuclear Power Plant (NPP) disaster. We examined the community dynamics of indigenous AMF colonizing roots of napiergrass (Pennisetum purpureum) in two different137Cs-contaminated land-use fields (grassland and paddy field) by an Illumina MiSeq sequencing investigation within a 30-km radius around the Fukushima-Daiichi NPP in 2013 (sampling year 1) and 2014 (sampling year 2). We found nine AMF families, including Glomeraceae, Gigasporaceae, Paraglomeraceae, Claroideoglomeraceae, Acaulosporaceae, Archeosporaceae, Ambisporaceae, Diversisporaceae and uncultured Glomeromycotina in roots. Glomeraceae was the most abundant in both grassland and paddy field, followed by Paraglomeraceae. The diversity of AMF in grassland and paddy field was higher in 2014 than in 2013. Furthermore, the AMF community structure was impacted by sampling year and land-use type. The AMF community structures colonizing napiergrass roots were also significantly impacted by land-use type and year throughout the 2-year investigation. To our knowledge, our results are the first report to reveal the community dynamics of indigenous AMF in the137Cs-contaminated fields around NPP.
Gene expression profiles during subclinical Mycobacterium avium subspecies paratuberculosis infection in sheep can predict disease outcome
Authors: Purdie Auriol C. , Plain Karren M. , Begg Douglas J. , de Silva Kumudika , Whittington Richard J. 
Published: June 2019

AbstractParatuberculosis in ruminants is caused by infection withMycobacterium aviumsubspeciesparatuberculosis(MAP) however exposure does not predetermine progression to clinical disease. The pathogenesis incorporates a subclinical phase during which MAP is capable of evading host immune responses through adaptation of host cellular immune mechanisms. Presented are results of transcriptomic analysis of Merino sheep experimentally exposed to MAP and repeatedly sampled over the subclinical phase, identifying genes consistently changed over time in comparison to unexposed controls and associated with different disease outcomes. MAP exposed sheep were classified as diseased 45% (n = 9) or resilient 55% (n = 11). Significant gene expression changes were identified in the white blood cells of paucibacillary (n = 116), multibacillary (n = 98) and resilient cohorts (n = 53) compared to controls. Members of several gene families were differentially regulated, including S100 calcium binding, lysozyme function, MHC class I and class II, T cell receptor and transcription factors. The microarray findings were validated by qPCR. These differentially regulated genes are presented as putative biomarkers of MAP exposure, or of the specified disease or resilience outcomes. Further,in silicofunctional analysis of genes suggests that experimental MAP exposure in Merino sheep results in adaptations to cellular growth, proliferation and lipid metabolism.
Incidence, predictors, and prognosis of premature discontinuation or switch of prasugrel or ticagrelor: the ATLANTIS - SWITCH study
Authors: Winter Max-Paul , von Lewinski Dirk , Wallner Markus , Prüller Florian , Kolesnik Ewald , Hengstenberg Christian , Siller-Matula Jolanta M. 
Published: June 2019

AbstractAim of the present study was to investigate the frequency and predictors of premature discontinuation or switch of ADP receptor blockers and its association with serious adverse events. For this purpose 571 consecutive ACS patients receiving ticagrelor (n = 258, 45%) or prasugrel (n = 313, 55%) undergoing PCI were enrolled in this prospective, observational, multicenter ATLANTIS-SWITCH substudy. Predictors of premature discontinuation or switch of antiplatelet therapy and their association with major adverse cardiovascular events and TIMI bleeding events were evaluated. Premature stop/switch was found in 72 (12.6%) patients: 34 (5.9%) stopped and 38 (6.7%) switched the ADP blocker. Ticagrelor treated patients were significantly more likely to stop/switch therapy as compared to prasugrel (15.9% vs. 9.2%, p = 0.016). We identified 4 independent predictors for stop/switch of ADP blocker: major surgery, need for oral anticoagulation (OAC), TIMI major bleeding and drug intolerance. TIMI major bleeding was a driver of stop/switch actions and occurred in 4.3% vs 0.2% in patients with vs without stop/switch (p = 0.001). The majority of stop/switch actions (75%) were physicians driven decisions. Importantly, stop/switch of therapy was not associated with increased risk of MACE (p = 0.936). In conclusion premature switch/stop of ADP blockers appears to be safe when mainly driven by physician’s decision and clinical indication.
Relationship between ETS Transcription Factor ETV1 and TGF-β-regulated SMAD Proteins in Prostate Cancer
Authors: Oh Sangphil , Shin Sook , Song Hoogeun , Grande Joseph P. , Janknecht Ralf 
Published: June 2019

AbstractThe ETS transcription factor ETV1 is frequently overexpressed in aggressive prostate cancer, which is one underlying cause of this disease. Accordingly, transgenic mice that prostate-specifically overexpress ETV1 develop prostatic intraepithelial neoplasia. However, progression to the adenocarcinoma stage is stifled in these mice, suggesting that inhibitory pathways possibly preclude ETV1 from exerting its full oncogenic potential. Here we provide evidence that TGF-β/SMAD signaling represents such an inhibitory pathway. First, we discovered that ETV1 forms complexes with SMAD4. Second, SMAD2, SMAD3 and SMAD4 overexpression impaired ETV1’s ability to stimulate gene transcription. Third, TGF-β1 inhibited ETV1-induced invasion by benign RWPE-1 prostate cells. Fourth, increased expression of SMAD3 and SMAD4 was observable in prostates of ETV1 transgenic mice. Conversely, we found that ETV1 may enhance TGF-β signaling in PC3 prostate cancer cells, revealing a different facet of the ETV1/TGF-β interplay. Altogether, these data provide more insights into the regulation and action of ETV1 and additionally suggest that TGF-β/SMAD signaling exerts its tumor suppressive activity, at least in part, by curtailing the oncogenic potential of ETV1 in prostatic lesions.
Hair Cortisol Measurement by an Automated Method
Authors: Gonzalez Diego , Jacobsen Dario , Ibar Carolina , Pavan Carlos , Monti José , Fernandez Machulsky Nahuel , Balbi Ayelen , Fritzler Analy , Jamardo Juan , Repetto Esteban M. , Berg Gabriela , Fabre Bibiana 
Published: June 2019

AbstractWe present the development of the first procedure for hair cortisol measurement through an automated method. Hair samples were obtained from 286 individuals. After cortisol extraction, samples were measured in a Siemens Immulite 2000 (Gwynedd, UK) automated chemoluminiscent immunoassay analyzer. Normal reference values were obtained from hair cortisol levels measured in 213 healthy individuals with low levels of stress. Hair cortisol concentration median was 55 pg/mg hair (2.5–97.5 percentile (40–128)) in healthy individuals with low levels of stress and 250 pg/mg hair (range 182–520) in stressed individuals. No significant differences were observed in hair cortisol levels between subjects with and without dye (40 (40–107) and 40 (40–155) pg/mg hair, respectively; p = 0.128). The novel procedure presented here shows an adequate analytical performance.
Influence of Initial Residual Stress on Growth and Pattern Creation for a Layered Aorta
Authors: Du Yangkun , Lü Chaofeng , Destrade Michel , Chen Weiqiu 
Published: June 2019

AbstractResidual stress is ubiquitous and indispensable in most biological and artificial materials, where it sustains and optimizes many biological and functional mechanisms. The theory of volume growth, starting from a stress-free initial state, is widely used to explain the creation and evolution of growth-induced residual stress and the resulting changes in shape, and to model how growing bio-tissues such as arteries and solid tumors develop a strategy of pattern creation according to geometrical and material parameters. This modelling provides promising avenues for designing and directing some appropriate morphology of a given tissue or organ and achieve some targeted biomedical function. In this paper, we rely on a modified, augmented theory to reveal how we can obtain growth-induced residual stress and pattern evolution of a layered artery by starting from an existing, non-zero initial residual stress state. We use experimentally determined residual stress distributions of aged bi-layered human aortas and quantify their influence by a magnitude factor. Our results show that initial residual stress has a more significant impact on residual stress accumulation and the subsequent evolution of patterns than geometry and material parameters. Additionally, we provide an essential explanation for growth-induced patterns driven by differential growth coupled to an initial residual stress. Finally, we show that initial residual stress is a readily available way to control growth-induced pattern creation for tissues and thus may provide a promising inspiration for biomedical engineering.
Characterization of mouse ocular response to a 35-day spaceflight mission: Evidence of blood-retinal barrier disruption and ocular adaptations
Authors: Mao Xiao W. , Nishiyama Nina C. , Byrum Stephanie D. , Stanbouly Seta , Jones Tamako , Drew Alyson , Sridharan Vijayalakshmi , Boerma Marjan , Tackett Alan J. , Zawieja David , Willey Jeffrey S. , Delp Michael , Pecaut Michael J. 
Published: June 2019

AbstractThe health risks associated with spaceflight-induced ocular structural and functional damage has become a recent concern for NASA. The goal of the present study was to characterize the effects of spaceflight and reentry to 1 g on the structure and integrity of the retina and blood-retinal barrier (BRB) in the eye. To investigate possible mechanisms, changes in protein expression profiles were examined in mouse ocular tissue after spaceflight. Ten week old male C57BL/6 mice were launched to the International Space Station (ISS) on Space-X 12 at the Kennedy Space Center (KSC) on August, 2017. After a 35-day mission, mice were returned to Earth alive. Within 38 +/− 4 hours of splashdown, mice were euthanized and ocular tissues were collected for analysis. Ground control (GC) and vivarium control mice were maintained on Earth in flight hardware or normal vivarium cages respectively. Repeated intraocular pressure (IOP) measurements were performed before the flight launch and re-measured before the mice were euthanized after splashdown. IOP was significantly lower in post-flight measurements compared to that of pre-flight (14.4–19.3 mmHg vs 16.3–20.3 mmHg) (p < 0.05) for the left eye. Flight group had significant apoptosis in the retina and retinal vascular endothelial cells compared to control groups (p < 0.05). Immunohistochemical analysis of the retina revealed that an increased expression of aquaporin-4 (AQP-4) in the flight mice compared to controls gave strong indication of disturbance of BRB integrity. There were also a significant increase in the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1) and a decrease in the expression of the BRB-related tight junction protein, Zonula occludens-1 (ZO-1). Proteomic analysis showed that many key proteins and pathways responsible for cell death, cell cycle, immune response, mitochondrial function and metabolic stress were significantly altered in the flight mice compared to ground control animals. These data indicate a complex cellular response that may alter retina structure and BRB integrity following long-term spaceflight.
Heterogenising study samples across testing time improves reproducibility of behavioural data
Authors: Bodden Carina , von Kortzfleisch Vanessa Tabea , Karwinkel Fabian , Kaiser Sylvia , Sachser Norbert , Richter S. Helene 
Published: June 2019

AbstractThe ongoing debate on the reproducibility crisis in the life sciences highlights the need for a rethinking of current methodologies. Since the trend towards ever more standardised experiments is at risk of causing highly idiosyncratic results, an alternative approach has been suggested to improve the robustness of findings, particularly from animal experiments. This concept, referred to as “systematic heterogenisation”, postulates increased external validity and hence, improved reproducibility by introducing variation systematically into a single experiment. However, the implementation of this concept in practice requires the identification of suitable heterogenisation factors. Here we show that the time of day at which experiments are conducted has a significant impact on the reproducibility of behavioural differences between two mouse strains, C57BL/6J and DBA/2N. Specifically, we found remarkably varying strain effects on anxiety, exploration, and learning, depending on the testing time, i.e. morning, noon or afternoon. In a follow-up simulation approach, we demonstrate that the systematic inclusion of two different testing times significantly improved reproducibility between replicate experiments. Our results emphasise the potential of time as an effective and easy-to-handle heterogenisation factor for single-laboratory studies. Its systematic variation likely improves reproducibility of research findings and hence contributes to a fundamental issue of experimental design and conduct in laboratory animal science.
A novel endogenous selection marker for the diatom Phaeodactylum tricornutum based on a unique mutation in phytoene desaturase 1
Authors: Taparia Yogesh , Zarka Aliza , Leu Stefan , Zarivach Raz , Boussiba Sammy , Khozin-Goldberg Inna 
Published: June 2019

AbstractPhaeodactylum tricornutumis a well-developed model diatom for both marine ecology and microalgal biotechnology, which has been enabled by the sequenced genome and the availability of gene delivery tools, such as biolistic transformation andE.coli-mediated conjugation. Till now, these tools have mainly relied on two selectable markers of bacterial origin which confer resistance to antibiotics Zeocin and nourseothricin. An alternative cost-effective and preferably endogenous selectable marker would facilitate gene stacking efforts through successive transformation or conjugation. We performed UV-mutagenesis ofP.tricornutumto obtain mutations in the phytoene desaturase (PDS) gene, conferring resistance to the bleaching herbicide norflurazon. Two mutants displaying high tolerance to norflurazon and carrying unique mutations in PtPDS1 (PHATRDRAFT_45735) were selected. These mutants revealed novel point mutations at a conserved residue Gly290 to Ser/Arg. Homology-based structural modeling of mutated PDS1, over a resolved crystallographic model of rice PDS1 complexed with norflurazon, suggests steric hindrance by bulkier residue substitution may confer herbicide resistance. We report the characterization of PtPDS1 mutants and the development of the first endogenous selectable marker in diatoms suitable for industrial strain development, with the added benefit of biocontainment. The plasmid carrying the mutated PDS1 as a selection marker and eGFP as a reporter was created. An optimized biolistic transformation system is reported which allowed the isolation of positive transgenic events at the rate of 96.7%. Additionally, the ease ofin vivoUV-mutagenesis may be employed as a strategy to create PDS-norflurazon-based selectable markers for other diatoms.
Broadband Optical Cavity Mode Measurements at Hz-Level Precision With a Comb-Based VIPA Spectrometer
Authors: Kowzan Grzegorz , Charczun Dominik , Cygan Agata , Trawiński Ryszard S. , Lisak Daniel , Masłowski Piotr 
Published: June 2019

AbstractOptical frequency comb spectrometers open up new avenues of investigation into molecular structure and dynamics thanks to their accuracy, sensitivity and broadband, high-speed operation. We combine broadband direct frequency comb spectroscopy with a dispersive spectrometer providing single-spectrum acquisition time of a few tens of milliseconds and high spectral resolution. We interleave a few tens of such comb-resolved spectra to obtain profiles of 14-kHz wide cavity resonances and determine their positions with precision of a few hertz. To the best of our knowledge, these are the most precise and highest resolution spectral measurements performed with a broadband spectrometer, either comb-based or non-comb-based. This result pushes the limits of broadband comb-based spectroscopy to Hz-level regime. As a demonstration of these capabilities, we perform simultaneous cavity-enhanced measurements of molecular absorption and dispersion, deriving the gas spectra from cavity mode widths and positions. Such approach is particularly important for gas metrology and was made possible by the Hz-level resolution of the system. The presented method should be especially applicable to monitoring of chemical kinetics in, for example, plasma discharges or measurements of narrow resonances in cold atoms and molecules.