bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic actions of FGF2 and bone marrow transplantation mitigate radiation-induced intestinal injury
Authors: Kim Byoung Hyuck , Jung Hee-Won , Seo Seok Hyun , Shin Hyemi , Kwon Jeanny , Suh Jae Myoung 
Published: March 2018

AbstractUnwanted radiological or nuclear exposure remains a public health risk for which effective therapeutic countermeasures are lacking. Here, we evaluated the efficacy of fibroblast growth factor-2 (FGF2) in treating radiation-induced gastrointestinal syndrome (RIGS) incurred by lethal whole-body irradiation (WBI) when administered in conjunction with bone marrow transplantation (BMT). In vitro experiments indicated FGF2 treatment increased proliferation, reduced apoptosis, and upregulated AKT–GSK3β/β–catenin signaling in irradiated IEC-6 cells. We next established and analyzed mice cohorts consisting of sham irradiation (Group Sh); 12 Gy WBI (Group A); WBI with BMT (Group B); WBI with FGF2 treatment (Group F); and WBI with BMT and FGF2 treatment (Group BF). At 2 weeks post-irradiation, Group BF showed a dramatic increase in survival over all other groups. Intestinal epithelium of Group BF, but not Group B or F, showed augmented proliferation, decreased apoptosis, and preserved crypt numbers and morphology. Furthermore, Group BF maintained intestinal barrier function with minimal inflammatory disturbances in a manner comparable to Group Sh. In accordance, transcriptomic analyses showed significant upregulation of intestinal barrier and stem cell markers in Group BF relative to Groups A and B. Taken together, parenteral FGF2 synergizes with BMT to confer potent mitigation against RIGS.
Hypoxia-Induced Matrix Metalloproteinase-13 Expression in Exosomes from Nasopharyngeal Carcinoma Enhances Metastases
Authors: Shan Ying , You Bo , Shi Si , Shi Wei , Zhang Zhenxin , Zhang Qicheng , Gu Miao , Chen Jing , Bao Lili , Liu Dong , You Yiwen 
Published: March 2018

AbstractExosomes are nano-vesicles secreted by tumor cells. Exosomes can transfer complex biological information and induce a diverse signaling response in a wide array of pathological conditions, such as hypoxia. Hypoxia is associated with aggressive phenotypes and poor outcomes in nasopharyngeal carcinoma (NPC) patients. Here, we analyzed the role of exosomes from hypoxic NPC cells in enhancing the metastases of normoxic cells in a hypoxia-induced factor-1α (HIF-1α)-dependent manner. HIF-1α rapidly accumulates and trans-activates hundreds of genes, such as matrix metalloproteinases (MMPs). We found that MMP-13 was over-expressed in exosomes and cells under hypoxic conditions. HIF-1α depletion in hypoxic CNE2 cells led to decreased MMP-13 levels in exosomes and significantly reduced cell migration and invasion. Moreover, exosomal MMP-13 significantly up-regulated Vimentin expression while decreasing E-cadherin levels in CNE2 cells in vitro and in vivo. Furthermore, MMP-13 levels were closely associated with HIF-1α expression (r = 0.679, P < 0.001), lymph node metastasis, clinical stage (all P < 0.05) and poor prognosis in NPC patients (P < 0.01). In conclusion, our findings suggest that the hypoxic exosomes were loaded with MMP-13, which could enhance migration and invasiveness and induce microenvironment changes to promote NPC aggressiveness.
Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
Authors: George Julie , Walter Vonn , Peifer Martin , Alexandrov Ludmil B. , Seidel Danila , Leenders Frauke , Maas Lukas , Müller Christian , Dahmen Ilona , Delhomme Tiffany M. , Ardin Maude , Leblay Noemie , Byrnes Graham , Sun Ruping , De Reynies Aurélien , McLeer-Florin Anne , Bosco Graziella , Malchers Florian , Menon Roopika , Altmüller Janine , Becker Christian , Nürnberg Peter , Achter Viktor , Lang Ulrich , Schneider Peter M. , Bogus Magdalena , Soloway Matthew G. , Wilkerson Matthew D. , Cun Yupeng , McKay James D. , Moro-Sibilot Denis , Brambilla Christian G. , Lantuejoul Sylvie , Lemaitre Nicolas , Soltermann Alex , Weder Walter , Tischler Verena , Brustugun Odd Terje , Lund-Iversen Marius , Helland Åslaug , Solberg Steinar , Ansén Sascha , Wright Gavin , Solomon Benjamin , Roz Luca , Pastorino Ugo , Petersen Iver , Clement Joachim H. , Sänger Jörg , Wolf Jürgen , Vingron Martin , Zander Thomas , Perner Sven , Travis William D. , Haas Stefan A. , Olivier Magali , Foll Matthieu , Büttner Reinhard , Hayes David Neil , Brambilla Elisabeth , Fernandez-Cuesta Lynnette , Thomas Roman K. 
Published: March 2018

AbstractPulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: “type I LCNECs” with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/NOTCHhigh, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.
Desmosomal cadherin association with Tctex-1 and cortactin-Arp2/3 drives perijunctional actin polymerization to promote keratinocyte delamination
Authors: Nekrasova Oxana , Harmon Robert M. , Broussard Joshua A. , Koetsier Jennifer L. , Godsel Lisa M. , Fitz Gillian N. , Gardel Margaret L. , Green Kathleen J. 
Published: March 2018

AbstractThe epidermis is a multi-layered epithelium that serves as a barrier against water loss and environmental insults. Its morphogenesis occurs through a tightly regulated program of biochemical and architectural changes during which basal cells commit to differentiate and move towards the skin’s surface. Here, we reveal an unexpected role for the vertebrate cadherin desmoglein 1 (Dsg1) in remodeling the actin cytoskeleton to promote the transit of basal cells into the suprabasal layer through a process of delamination, one mechanism of epidermal stratification. Actin remodeling requires the interaction of Dsg1 with the dynein light chain, Tctex-1 and the actin scaffolding protein, cortactin. We demonstrate that Tctex-1 ensures the correct membrane compartmentalization of Dsg1-containing desmosomes, allowing cortactin/Arp2/3-dependent perijunctional actin polymerization and decreasing tension at E-cadherin junctions to promote keratinocyte delamination. Moreover, Dsg1 is sufficient to enable simple epithelial cells to exit a monolayer to form a second layer, highlighting its morphogenetic potential.
Author Correction: Energy use and life cycle greenhouse gas emissions of drones for commercial package delivery
Authors: Stolaroff Joshuah K. , Samaras Constantine , O’Neill Emma R. , Lubers Alia , Mitchell Alexandra S. , Ceperley Daniel 
Published: March 2018

In the original version of this Article, the first sentence of the sixth paragraph of the “Comparing emissions” section, the Results originally incorrectly read as ‘In the base case, delivery of a small (0.5 kg) package with the small quadrotor drone has lower impacts than delivery by diesel truck, ranging from a 59% reduction in GHGs in California, to a 17% reduction in Missouri’. The correct version states ‘54%’ instead of ‘59%’ and ‘23%’ instead of ‘17%’.The fourth sentence of the same paragraph originally incorrectly read as ‘In the base case, delivery of a medium-sized (8 kg) package has 17% lower GHGs than delivery by truck in California, is about equivalent to delivery trucks for the U.S. average electricity mix, but has 77% higher GHGs than truck delivery in Missouri, which has a carbon-intensive electricity grid’. The correct version states ‘In the base case, delivery of a medium-sized (8 kg) package has 9% lower GHGs than delivery by truck in California, is about 24% higher than delivery trucks for the U.S. average electricity mix, and has 50% higher GHGs than truck delivery in Missouri, which has a carbon-intensive electricity grid.The last sentence of the seventh paragraph of the same section originally incorrectly read as ‘Because of the importance of electricity used to power the octocopter, charging with low-carbon electricity of 200 g GHG/kWh can reduce delivered package GHGs by 34% compared to diesel trucks’. The correct version states ‘37%’ instead of ‘34%’.These errors have been corrected in both the PDF and HTML versions of the Article.
Structural change as a key component for agricultural non-CO2 mitigation efforts
Authors: Frank Stefan , Beach Robert , Havlík Petr , Valin Hugo , Herrero Mario , Mosnier Aline , Hasegawa Tomoko , Creason Jared , Ragnauth Shaun , Obersteiner Michael 
Published: March 2018

AbstractAgriculture is the single largest source of anthropogenic non-carbon dioxide (non-CO2) emissions. Reaching the climate target of the Paris Agreement will require significant emission reductions across sectors by 2030 and continued efforts thereafter. Here we show that the economic potential of non-CO2 emissions reductions from agriculture is up to four times as high as previously estimated. In fact, we find that agriculture could achieve already at a carbon price of 25 $/tCO2eq non-CO2 reductions of around 1 GtCO2eq/year by 2030 mainly through the adoption of technical and structural mitigation options. At 100 $/tCO2eq agriculture could even provide non-CO2 reductions of 2.6 GtCO2eq/year in 2050 including demand side efforts. Immediate action to favor the widespread adoption of technical options in developed countries together with productivity increases through structural changes in developing countries is needed to move agriculture on track with a 2 °C climate stabilization pathway.
Molecular typing of Mycobacterium kansasii using pulsed-field gel electrophoresis and a newly designed variable-number tandem repeat analysis
Authors: Bakuła Zofia , Brzostek Anna , Borówka Paulina , Żaczek Anna , Szulc-Kiełbik Izabela , Podpora Agata , Parniewski Paweł , Strapagiel Dominik , Dziadek Jarosław , Proboszcz Małgorzata , Bielecki Jacek , van Ingen Jakko , Jagielski Tomasz 
Published: March 2018

AbstractMolecular epidemiological studies of Mycobacterium kansasii are hampered by the lack of highly-discriminatory genotyping modalities. The purpose of this study was to design a new, high-resolution fingerprinting method for M. kansasii. Complete genome sequence of the M. kansasii ATCC 12478 reference strain was searched for satellite-like repetitive DNA elements comprising tandem repeats. A total of 24 variable-number tandem repeat (VNTR) loci were identified with potential discriminatory capacity. Of these, 17 were used to study polymorphism among 67 M. kansasii strains representing six subtypes (I-VI). The results of VNTR typing were compared with those of pulsed-field gel electrophoresis (PFGE) with AsnI digestion. Six VNTRs i.e. (VNTR 1, 2, 8, 14, 20 and 23) allow to differentiate analyzed strains with the same discriminatory capacities as use of a 17-loci panel. VNTR typing and PFGE in conjunction revealed 45 distinct patterns, including 11 clusters with 33 isolates and 34 unique patterns. The Hunter-Gaston’s discriminatory index was 0.95 and 0.66 for PFGE and VNTR typing respectively, and 0.97 for the two methods combined. In conclusion, this study delivers a new typing scheme, based on VNTR polymorphism, and recommends it as a first-line test prior to PFGE analysis in a two-step typing strategy for M. kansasii.
Large sub-clonal variation in Phytophthora infestans from recent severe late blight epidemics in India
Authors: Dey Tanmoy , Saville Amanda , Myers Kevin , Tewari Susanta , Cooke David E. L. , Tripathy Sucheta , Fry William E. , Ristaino Jean B. , Guha Roy Sanjoy 
Published: March 2018

AbstractThe population structure of the Phytophthora infestans populations that caused the recent 2013–14 late blight epidemic in eastern India (EI) and northeastern India (NEI) was examined. The data provide new baseline information for populations of P. infestans in India. A migrant European 13_A2 genotype was responsible for the 2013–14 epidemic, replacing the existing populations. Mutations have generated substantial sub-clonal variation with 24 multi-locus genotypes (MLGs) found, of which 19 were unique variants not yet reported elsewhere globally. Samples from West Bengal were the most diverse and grouped alongside MLGs found in Europe, the UK and from neighbouring Bangladesh but were not linked directly to most samples from south India. The pathogen population was broadly more aggressive on potato than on tomato and resistant to the fungicide metalaxyl. Pathogen population diversity was higher in regions around the international borders with Bangladesh and Nepal. Overall, the multiple shared MLGs suggested genetic contributions from UK and Europe in addition to a sub-structure based on the geographical location within India. Our data indicate the need for improved phytosanitary procedures and continuous surveillance to prevent the further introduction of aggressive lineages of P. infestans into the country.
Effects of Phytase Transgenic Maize on the Physiological and Biochemical Responses and the Gut Microflora Functional Diversity of Ostrinia furnacalis
Authors: Xu Xiao Hui , Guo Yinghui , Sun Hongwei , Li Fan , Yang Shuke , Gao Rui , Lu Xingbo 
Published: March 2018

AbstractTransgenic maize hybrids that express the Aspergillus niger phyA2 gene could significantly improve phosphorus bioavailability to poultry and livestock. However, little information has been reported about the effects of phytase transgenic maize on the Asian corn borer (ACB), Ostrinia furnacalis (Guenée). This study provides valuable information about the physiological, biochemical and gut microflora functional diversity changes of ACBs fed phytase transgenic maize. The weights, survival rates, in vivo protein contents, activities of two detoxification enzymes and three antioxidant enzymes of ACBs fed phytase transgenic maize exhibited no significant differences to those fed non-transgenic maize. Functional diversities of the gut microflora communities of ACBs were not affected by different fodder treatments, but significant differences were observed between different generations of ACBs. Our study provides useful information about the biochemical responses and gut microflora community functional diversities of ACBs fed phytase transgenic maize firstly and the results will help to assess the potential effects of phytase transgenic maize on other target and non-target arthropods in the future.
Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer
Authors: Harder Nathalie , Athelogou Maria , Hessel Harald , Brieu Nicolas , Yigitsoy Mehmet , Zimmermann Johannes , Baatz Martin , Buchner Alexander , Stief Christian G. , Kirchner Thomas , Binnig Gerd , Schmidt Günter , Huss Ralf 
Published: March 2018

AbstractTissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low- and intermediate-risk prostate cancer patients (Gleason scores 6–7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach.
Finite Dimension: A Mathematical Tool to Analise Glycans
Authors: Alonso J. M. , Arroyuelo A. , Garay P. G. , Martin O. A. , Vila J. A. 
Published: March 2018

AbstractThere is a need to develop widely applicable tools to understand glycan organization, diversity and structure. We present a graph-theoretical study of a large sample of glycans in terms of finite dimension, a new metric which is an adaptation to finite sets of the classical Hausdorff “fractal” dimension. Every glycan in the sample is encoded, via finite dimension, as a point of Glycan Space, a new notion introduced in this paper. Two major outcomes were found: (a) the existence of universal bounds that restrict the universe of possible glycans and show, for instance, that the graphs of glycans are a very special type of chemical graph, and (b) how Glycan Space is related to biological domains associated to the analysed glycans. In addition, we discuss briefly how this encoding may help to improve search in glycan databases.
Author Correction: Myeloperoxidase is not a good biomarker for preeclampsia prediction
Authors: Rocha-Penha L. , Bettiol H. , Barbieri M. A. , Cardoso V. C. , Cavalli R. C. , Sandrim V. C. 
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
The Boring Billion, a slingshot for Complex Life on Earth
Authors: Mukherjee Indrani , Large Ross R. , Corkrey Ross , Danyushevsky Leonid V. 
Published: March 2018

AbstractThe period 1800 to 800 Ma (“Boring Billion”) is believed to mark a delay in the evolution of complex life, primarily due to low levels of oxygen in the atmosphere. Earlier studies highlight the remarkably flat C, Cr isotopes and low trace element trends during the so-called stasis, caused by prolonged nutrient, climatic, atmospheric and tectonic stability. In contrast, we suggest a first-order variability of bio-essential trace element availability in the oceans by combining systematic sampling of the Proterozoic rock record with sensitive geochemical analyses of marine pyrite by LA-ICP-MS technique. We also recall that several critical biological evolutionary events, such as the appearance of eukaryotes, origin of multicellularity & sexual reproduction, and the first major diversification of eukaryotes (crown group) occurred during this period. Therefore, it appears possible that the period of low nutrient trace elements (1800–1400 Ma) caused evolutionary pressures which became an essential trigger for promoting biological innovations in the eukaryotic domain. Later periods of stress-free conditions, with relatively high nutrient trace element concentration, facilitated diversification. We propose that the “Boring Billion” was a period of sequential stepwise evolution and diversification of complex eukaryotes, triggering evolutionary pathways that made possible the later rise of micro-metazoans and their macroscopic counterparts.
In tendons, differing physiological requirements lead to functionally distinct nanostructures
Authors: Quigley Andrew S. , Bancelin Stéphane , Deska-Gauthier Dylan , Légaré François , Kreplak Laurent , Veres Samuel P. 
Published: March 2018

AbstractThe collagen-based tissues of animals are hierarchical structures: even tendon, the simplest collagenous tissue, has seven to eight levels of hierarchy. Tailoring tissue structure to match physiological function can occur at many different levels. We wanted to know if the control of tissue architecture to achieve function extends down to the nanoscale level of the individual, cable-like collagen fibrils. Using tendons from young adult bovine forelimbs, we performed stress-strain experiments on single collagen fibrils extracted from tendons with positional function, and tendons with energy storing function. Collagen fibrils from the two tendon types, which have known differences in intermolecular crosslinking, showed numerous differences in their responses to elongation. Unlike those from positional tendons, fibrils from energy storing tendons showed high strain stiffening and resistance to disruption in both molecular packing and conformation, helping to explain how these high stress tissues withstand millions of loading cycles with little reparative remodeling. Functional differences in load-bearing tissues are accompanied by important differences in nanoscale collagen fibril structure.
Size Exclusion Chromatography Method for Purification of Nicotinamide Mononucleotide (NMN) from Bacterial Cells
Authors: Marinescu George Cătălin , Popescu Roua-Gabriela , Dinischiotu Anca 
Published: March 2018

AbstractOver 12% of the world’s health resources are spent on treating diabetes, as high blood glucose is the third cause of mortality worldwide. Insulin resistance is the basis of the most common form of diabetes: type 2 diabetes. Recent animal studies report successful attempts at reversing type 2 diabetes by the administering of the NAD+precursor nicotinamide mononucleotide (NMN). However, the current high price of this molecule urges for more efficient and cost-effective production methods. This work proposes a method for purifying NMN by Size Exclusion Chromatography (SEC) on silica with a covalently attached coating of poly(2-hydroxyethyl aspartamide) (PolyHEA) stationary phase using an isocratic elution with a denaturing mobile phase (50 mM formic acid) from a complex molecular mixture such as a fermentation broth. The eluted peaks were identified by UV-Vis analysis and confirmed with ESI+ mass spectrometry and a HPLC reversed-phase method. The proposed SEC method is simple, patent-free, directly applicable for industrial production with a minimum scale up effort. The need for multiple chromatographic steps is eliminated and the lysate filtration and clarification steps are simplified. Substantial reduction in NMN production costs and increased purity of NMN to the level suitable for usage in humans are expected.