bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response
Authors: Fermaintt Charles S. , Sano Kanae , Liu Zhida , Ishii Nozomi , Seino Junichi , Dobbs Nicole , Suzuki Tadashi , Fu Yang-Xin , Lehrman Mark A. , Matsuo Ichiro , Yan Nan 
Published: May 2019

AbstractGlycans from microbial pathogens are well known pathogen-associated molecular patterns that are recognized by the host immunity; however, little is known about whether and how mammalian self-glycans activate the host immune response, especially in the context of autoimmune disease. Using biochemical fractionation and two-dimensional HPLC, we identify an abundant and bioactive free glycan, the Manβ1-4GlcNAc disaccharide in TREX1-associated autoimmune diseases. We report that both monosaccharide residues and the β1-4 linkage are critical for bioactivity of this disaccharide. We also show that Manβ1-4GlcNAc is produced by oligosaccharyltransferase hydrolysis of lipid-linked oligosaccharides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes. Furthermore, synthetic Manβ1-4GlcNAc disaccharide stimulates a broad immune response in vitro, which is in part dependent on the STING-TBK1 pathway, and enhances antibody response in vivo. Together, our data identify Manβ1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases.
Publisher Correction: High mitogenic stimulation arrests angiogenesis
Authors: Pontes-Quero Samuel , Fernández-Chacón Macarena , Luo Wen , Lunella Federica Francesca , Casquero-Garcia Verónica , Garcia-Gonzalez Irene , Hermoso Ana , Rocha Susana F. , Bansal Mayank , Benedito Rui 
Published: May 2019

The original version of this Article contained errors in Fig. 8. In panel a, the labels ‘VEGF’, ‘Notch’, ‘p21’, and ‘P-ERK’ were inadvertently omitted. This has been corrected in the PDF and HTML versions of the Article.
Publisher Correction: Tear resistance of soft collagenous tissues
Authors: Bircher Kevin , Zündel Manuel , Pensalfini Marco , Ehret Alexander E. , Mazza Edoardo 
Published: May 2019

The original version of this Article contained errors in the ‘Computational material models’ section of the Methods in which some values were displayed with incorrect units. As a result of this, a number of changes have been made to both the PDF and the HTML versions of the Article. A full description of these changes is available online and can be accessed via a link at the top of the Article.
Epidermal Growth Factor Stimulates Transforming Growth Factor-Beta Receptor Type II Expression In Corneal Epithelial Cells
Authors: Shu Daisy Y. , Hutcheon Audrey E. K. , Zieske James D. , Guo Xiaoqing 
Published: May 2019

AbstractWe previously demonstrated that inhibition of epidermal growth factor receptor (EGFR) slowed corneal epithelial migration. Here we examine the effect of EGF on transforming growth factor-beta receptor II (TGF-βRII) in a corneal wound-healing model and primary human corneal epithelial cells (pHCE). Corneal debridement wounds were made and allowed to heal ± Tyrphostin AG1478 (EGFR inhibitor), and assayed for EGFR activation and EGFR and TGF-βRII localization. Primary HCE were treated with EGF ± U0126 (MEK inhibitor) and assayed for TGF-βRII expression. EGFR activation was maximal 15 minutes after wounding and localized in the migrating epithelial cells. TGF-βRII localization was also observed in the migrating epithelium and was reduced when EGFR was blocked. When pHCE were treated with EGF for 6 hours, the cells produced enhanced levels of TGF-βRII, which was blocked by U0126. Downstream signaling pathways of MEK (p38MAPKand ERK1/2MAPK) were then examined, and TGF-β1 and EGF were found to have differential effects on the phosphorylation of p38 and ERK1/2, with TGF-β1 upregulating p-p38 but not pERK1/2 and EGF upregulating pERK1/2 but not p-p38. Taken together, these data indicate that EGF stimulates TGF-βRII through ERK1/2 and EGFR signaling, suggesting interplay between EGF- and TGF-β-signaling pathways during corneal wound repair.
Rapid nondestructive measurement of bacterial cultures with 3D interferometric imaging
Authors: Larimer Curtis , Brann Michelle R. , Powell Joshua D. , Marshall Matthew J. , Suter Jonathan D. , Addleman R. Shane 
Published: May 2019

AbstractThe agar culture plate has played a crucial role in bacteriology since the origins of the discipline and is a staple bioanalytical method for efforts ranging from research to standard clinical diagnostic tests. However, plating, inoculating, and waiting for microbes to develop colonies that are visible is time-consuming. In this work, we demonstrate white-light interferometry (WLI) as a practical tool for accelerated and improved measurement of bacterial cultures. High resolution WLI surface profile imaging was used for nondestructive characterization and counting of bacterial colonies on agar before they became visible to the naked eye. The three-dimensional (3D) morphology of Gram-negative (Pseudomonas fluorescens) and Gram-positive (Bacillus thuringiensis) bacterial species were monitored with WLI over time by collecting surface profiles of colonies on agar plates with high vertical resolution (3–5 nanometers) and large field of view (3–5 mm). This unique combination of sensitive vertical resolution and large field of view uniquely provided by WLI enables measurement of colony morphologies and nondestructive monitoring of hundreds of microcolonies. Individual bacteria were imaged within the first few hours after plating and colonies were accurately counted with results comparing favorably to counts made by traditional methods that require much longer wait times. Nondestructive imaging was used to track single cells multiplying into small colonies and the volume changes over time in these colonies were used to measure their growth rates. Based on the results herein, bioimaging with WLI was demonstrated as a novel rapid bacterial culture assay with several advantageous capabilities. Fast nondestructive counting of colony-forming units in a culture and simultaneous measurement of bacterial growth rates and colony morphology with this method may be beneficial in research and clinical applications where current methods are either too slow or are destructive.
Female-specific decreases in alcohol binge-like drinking resulting from GABAA receptor delta-subunit knockdown in the VTA
Authors: Darnieder L. M. , Melón L. C. , Do T. , Walton N. L. , Miczek K. A. , Maguire J. L. 
Published: May 2019

AbstractBinge drinking is short-term drinking that achieves blood alcohol levels of 0.08 g/dl or above. It exhibits well-established sex differences in GABAergic inhibitory neurotransmission, including extrasynaptic δ subunit-containing GABAA receptors (δ-GABAARs) that mediate tonic inhibition, or synaptic γ2-containing GABAARs which underlie fast, synaptic, phasic inhibition have been implicated in sex differences in binge drinking. Ovarian hormones regulate δ-GABAARs, further implicating these receptors in potential sex differences. Here, we explored the contribution of extrasynaptic δ-GABAARs to male and female binge-like drinking in a critical area of mesolimbic circuitry—the ventral tegmental area (VTA). Quantitative PCR revealed higher Gabrd transcript levels and larger tonic currents in the VTA of females compared to males. In contrast, male and female Gabrg2 transcript levels and measures of phasic inhibition were equivalent. Intra-VTA infusion of AAV-Cre-GFP in floxed Gabrd mice downregulated δ-GABAARs and decreased binge-like drinking in females. There was no significant difference in either male or female mice after GABAAR γ2 subunit reduction in the VTA following AAV-Cre-GFP infusion in floxed Gabrg2 mice. Collectively, these findings suggest sex differences and GABAAR subunit specificity in alcohol intake.
A novel anti Candida albicans drug screening system based on high-throughput microfluidic chips
Authors: Qiang Le , Guo Jing , Han Yingkuan , Jiang Jianfeng , Su Xiaowen , Liu Hong , Qi Qingguo , Han Lin 
Published: May 2019

AbstractDue to the antibacterial resistance crisis, developing new antibacterials is of particular interest. In this study, we combined the antifungal drug amphotericin B with 50,520 different small molecule compounds obtained from the Chinese National Compound Library in an attempt to improve its efficacy against Candida albicans persister cells. To systematically study the antifungal effect of each compound, we utilized custom-designed high-throughput microfluidic chips. Our microfluidic chips contained microchannels ranging from 3 µm to 5 µm in width to allow Candida albicans cells to line up one-by-one to facilitate fluorescence-microscope viewing. After screening, we were left with 10 small molecule compounds that improved the antifungal effects of amphotericin B more than 30% against Candida albicans persister cells.
Long-range depth imaging using a single-photon detector array and non-local data fusion
Authors: Chan Susan , Halimi Abderrahim , Zhu Feng , Gyongy Istvan , Henderson Robert K. , Bowman Richard , McLaughlin Stephen , Buller Gerald S. , Leach Jonathan 
Published: May 2019

AbstractThe ability to measure and record high-resolution depth images at long stand-off distances is important for a wide range of applications, including connected and automotive vehicles, defense and security, and agriculture and mining. In LIDAR (light detection and ranging) applications, single-photon sensitive detection is an emerging approach, offering high sensitivity to light and picosecond temporal resolution, and consequently excellent surface-to-surface resolution. The use of large format CMOS (complementary metal-oxide semiconductor) single-photon detector arrays provides high spatial resolution and allows the timing information to be acquired simultaneously across many pixels. In this work, we combine state-of-the-art single-photon detector array technology with non-local data fusion to generate high resolution three-dimensional depth information of long-range targets. The system is based on a visible pulsed illumination system at a wavelength of 670 nm and a 240 × 320 array sensor, achieving sub-centimeter precision in all three spatial dimensions at a distance of 150 meters. The non-local data fusion combines information from an optical image with sparse sampling of the single-photon array data, providing accurate depth information at low signature regions of the target.
Efficacy of Recombinant Human BMP2 and PDGF-BB in Orofacial Bone Regeneration: A Systematic Review and Meta-analysis
Authors: Li Feifei , Yu Fanyuan , Liao Xueyang , Wu Chenzhou , Wang Yitian , Li Chunjie , Lou Feng , Li Boer , Yin Bei , Wang Chenglin , Ye Ling 
Published: May 2019

AbstractWith the rapid development of tissue engineering therapies, there is a growing interest in the application of recombinant human growth factors (rhGFs) to regenerate human orofacial bones. However, despite reports of their ability to promote orofacial bone regeneration in animal experiments, their benefits in human clinical treatments remain unclear. Furthermore, the appropriate concentrations or indications of a specific rhGF remain ambiguous. Therefore it is essential to collect data from diverse clinical trials to evaluate their effects more precisely. Here we reviewed randomized clinical trials (RCT) that focused on the utilization of rhGFs in orofacial bone regeneration. Data from included studies were extracted, pooled and then quantitatively analyzed according to a pre-established protocol. Our results indicate that all current concentrations of rhBMP-2 produces insufficient effect on promoting either tooth extraction socket healing, sinus augmentation or reconstruction of alveolar clefts. However, 0.3 mg/ml rhPDGF-BB promotes the healing of tooth extraction sockets, though the effect does not reach a level of statistical significance. Summarily, we recommend concentrations of 0.3 mg/ml rhPDGF-BB only for the healing of tooth extraction sockets.
Contrasting methane emissions from upstream and downstream rivers and their associated subtropical reservoir in eastern China
Authors: Yang Le 
Published: May 2019

AbstractSubtropical reservoirs are an important source of atmospheric methane (CH4). This study investigated the spatiotemporal variability of bubble and diffusive CH4 emissions from a subtropical reservoir, including its upstream and downstream rivers, in eastern China. There was no obvious seasonal variation in CH4 emissions from the main reservoir, which increased slightly from the first half year to the next half year. In the upstream river, CH4 emissions were low from February to June and fluctuated widely from July to January due to bubble activity. In the downstream river, CH4 emissions were lowest in February, which was possibly influenced by the low streamflow rate from the reservoir (275 m3 s−1) and a short period of mixing. There was spatial variability in CH4 emissions, where fluxes were highest from the upstream river (3.65 ± 3.24 mg CH4 m−2 h−1) and lowest from the main reservoir (0.082 ± 0.061 mg CH4 m−2 h−1), and emissions from the downstream river were 0.49 ± 0.20 mg CH4 m−2 h−1. Inflow rivers are hot spots in bubble CH4 emissions that should be examined using field-sampling strategies. This study will improve the accuracy of current and future estimations of CH4 emissions from hydroelectric systems and will help guide mitigation strategies for greenhouse gas emissions.
Neoplastic Transformation of Human Mesenchymal Stromal Cells Mediated via LIN28B
Authors: Vishnubalaji Radhakrishnan , Elango Ramesh , Al-Toub Mashael , Manikandan Muthurangan , Al-Rikabi Ammar , Harkness Linda , Ditzel Nicholas , Atteya Muhammad , Hamam Rimi , Alfayez Musaad , Aldahmash Abdullah , Kassem Moustapha , Alajez Nehad M. 
Published: May 2019

AbstractBone marrow stromal (Mesenchymal) stem cells (MSCs) are multipotent bone cells capable of differentiating into mesoderm-type cells, such as osteoblasts and adipocytes. Existing evidence suggests that transformation of MSCs gives rise to sarcoma. In order to identify the molecular mechanism leading to spontaneous transformation of human bone marrow MSCs (hBMSCs), we performed comprehensive microRNA (miRNA) and mRNA profiling in the transformed hBMSC-Tum line compared to the parental clone. As a result, we identified multiple dysregulated molecular networks associated with the hBMSC transformed phenotype. LIN28B was upregulated 177.0-fold in hBMSC-Tum, which was associated with marked reduction in LET-7 expression and upregulated expression of its target HMGA2. Targeted depletion of LIN28B or exogenous expression of LET-7b suppressed hBMSC-Tum proliferation, colony formation, and migration. On the other hand, forced expression of LIN28B promoted malignant transformation of parental hBMSC cells as shown by enhanced in vitro colony formation, doxorubicin resistance, and in vivo tumor formation in immunocompromised mice. Analysis of LIN28B and HMGA2 expression levels in cohorts from The Cancer Genome Atlas sarcoma dataset revealed a strong inverse-relationship between elevated expression and overall survival (OS) in 260 patients (p = 0.005) and disease-free survival (DFS) in 231 patients (p = 0.02), suggesting LIN28B and HMGA2 are important regulators of sarcoma biology. Our results highlight an important role for the LIN28B/LET-7 axis in human sarcoma pathogenesis and suggest that the therapeutic targeting of LIN28B may be relevant for patients with sarcoma.
The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activity
Authors: Pinneh Elizabeth C. , Mina John G. , Stark Michael J. R. , Lindell Stephen D. , Luemmen Peter , Knight Marc R. , Steel Patrick G. , Denny Paul W. 
Published: May 2019

AbstractResistance to 157 different herbicides and 88% of known sites of action has been observed, with many weeds resistant to two or more modes. Coupled with tighter environmental regulation, this demonstrates the need to identify new modes of action and novel herbicides. The plant sphingolipid biosynthetic enzyme, inositol phosphorylceramide synthase (IPCS), has been identified as a novel, putative herbicide target. The non-mammalian nature of this enzyme offers the potential of discovering plant specific inhibitory compounds with minimal impact on animals and humans, perhaps leading to the development of new non-toxic herbicides. The best characterised and most highly expressed isoform of the enzyme in the model-dicot Arabidopsis, AtIPCS2, was formatted into a yeast-based assay which was then utilized to screen a proprietary library of over 11,000 compounds provided by Bayer AG. Hits from this screen were validated in a secondary in vitro enzyme assay. These studies led to the identification of a potent inhibitor that showed selectivity for AtIPCS2 over the yeast orthologue, and activity against Arabidopsis seedlings. This work highlighted the use of a yeast-based screening assay to discover herbicidal compounds and the status of the plant IPCS as a novel herbicidal target.
The diguanylate cyclase AdrA regulates flagellar biosynthesis in Pseudomonas fluorescens F113 through SadB
Authors: Muriel Candela , Blanco-Romero Esther , Trampari Eleftheria , Arrebola Eva , Durán David , Redondo-Nieto Miguel , Malone Jacob G. , Martín Marta , Rivilla Rafael 
Published: May 2019

AbstractFlagellum mediated motility is an essential trait for rhizosphere colonization by pseudomonads. Flagella synthesis is a complex and energetically expensive process that is tightly regulated. In Pseudomonas fluorescens, the regulatory cascade starts with the master regulatory protein FleQ that is in turn regulated by environmental signals through the Gac/Rsm and SadB pathways, which converge in the sigma factor AlgU. AlgU is required for the expression of amrZ, encoding a FleQ repressor. AmrZ itself has been shown to modulate c-di-GMP levels through the control of many genes encoding enzymes implicated in c-di-GMP turnover. This cyclic nucleotide regulates flagellar function and besides, the master regulator of the flagellar synthesis signaling pathway, FleQ, has been shown to bind c-di-GMP. Here we show that AdrA, a diguanylate cyclase regulated by AmrZ participates in this signaling pathway. Epistasis analysis has shown that AdrA acts upstream of SadB, linking SadB with environmental signaling. We also show that SadB binds c-di-GMP with higher affinity than FleQ and propose that c-di-GMP produced by AdrA modulates flagella synthesis through SadB.
The Effects of Switching Non-Spatial Attention During Conversational Turn Taking
Authors: Lin Gaven , Carlile Simon 
Published: May 2019

AbstractThis study examined the effect of a change in target voice on word recall during a multi-talker conversation. Two experiments were conducted using matrix sentences to assess the cost of a single endogenous switch in non-spatial attention. Performance in a yes-no recognition task was significantly worse when a target voice changed compared to when it remained the same after a turn-taking gap. We observed a decrease in target hit rate and sensitivity, and an increase in masker confusion errors following a change in voice. These results highlight the cognitive demands of not only engaging attention on a new talker, but also of disengaging attention from a previous target voice. This shows that exposure to a voice can have a biasing effect on attention that persists well after a turn-taking gap. A second experiment showed that there was no change in switching performance using different talker combinations. This demonstrates that switching costs were consistent and did not depend on the degree of acoustic differences in target voice characteristics.
Induced androgenetic development in rainbow trout and transcriptome analysis of irradiated eggs
Authors: Ocalewicz Konrad , Gurgul Artur , Pawlina-Tyszko Klaudia , Szmatoła Tomasz , Jasielczuk Igor , Bugno-Poniewierska Monika , Dobosz Stefan 
Published: May 2019

AbstractIonizing radiation is administered to damage nuclear genome in fish eggs during induced androgenesis. In this study, we examined whether 350 Gy of X-ray applied to damage chromosomes in the rainbow trout eggs affects maternal RNA. Shortly after irradiation, we did not find any symptoms of RNA degradation in the treated eggs. Significant (p < 0.01) differences between non-irradiated and irradiated eggs concerned only a few transcripts including increased expression of immediate early response 2 (IER2) and early growth response 1 (EGR1) genes observed in the irradiated eggs. Both genes belong to the group of “immediate early genes” that respond quickly to the diverse extracellular stimuli. Elevated expression of these genes was accompanied by decreased level of ssa-miR-10b-5p and ssa-miR-21b-5p (p < 0.05), for which IER2 and EGR1 are target genes. The level of RNA in the fertilized irradiated eggs was highly significantly lower than in the non-irradiated eggs (p < 0.001) and in the unfertilized irradiated eggs (p < 0.0001). However, transcriptome profiles of fertilized non-irradiated eggs and fertilized irradiated eggs did not differ significantly. Thus, we assume that reduced abundance of mRNA in the fertilized irradiated eggs was associated with post-translational degradation and clearance of the maternal transcripts rather than from the irradiation of eggs.
Structural and biochemical characterization of Rv0187, an O-methyltransferase from Mycobacterium tuberculosis
Authors: Lee Sanghyun , Kang Jihoon , Kim Jungwook 
Published: May 2019

AbstractCatechol O-methyltransferase (COMT) is widely distributed in nature and installs a methyl group onto one of the vicinal hydroxyl groups of a catechol derivative. Enzymes belonging to this family require two cofactors for methyl transfer: S-adenosyl-l-methionine as a methyl donor and a divalent metal cation for regiospecific binding and activation of a substrate. We have determined two high-resolution crystal structures of Rv0187, one of three COMT paralogs from Mycobacterium tuberculosis, in the presence and absence of cofactors. The cofactor-bound structure clearly locates strontium ions and S-adenosyl-l-homocysteine in the active site, and together with the complementary structure of the ligand-free form, it suggests conformational dynamics induced by the binding of cofactors. Examination of in vitro activities revealed promiscuous substrate specificity and relaxed regioselectivity against various catechol-like compounds. Unexpectedly, mutation of the proposed catalytic lysine residue did not abolish activity but altered the overall landscape of regiospecific methylation.