bluuebunny/crossref_metadata_2025_split huggingface dataset:
Klotho enhances FoxO3-mediated manganese superoxide dismutase expression by negatively regulating PI3K/AKT pathway during tacrolimus-induced oxidative stress
Authors: Lim Sun Woo , Jin Long , Luo Kang , Jin Jian , Shin Yoo Jin , Hong Sung Yi , Yang Chul Woo 
Published: August 2017

AbstractMammalian members of the forkhead box protein O (FoxO) class of transcription factors are implicated in the regulation of oxidative stress, and FoxO proteins are negatively regulated by the phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway. We examined the effect of Klotho on the PI3K/AKT pathway and manganese superoxide dismutase (MnSOD) during tacrolimus (Tac)-induced oxidative stress. Klotho-treated mice showed decreased Tac-induced oxidative stress accompanied by functional and histological improvements. Klotho inhibited the PI3K/AKT-mediated phosphorylation of FoxO3a and enhanced FoxO3a binding to the MnSOD promoter. Klotho increased MnSOD mRNA and protein expression in mitochondria. In addition, Klotho reduced Tac-induced mitochondrial dysfunction and decreased mitochondrial reactive oxygen species production, and these effects were enhanced by blocking PI3K activity with LY294002. Collectively, our data showed that Klotho protects Tac-induced oxidative stress by negatively regulating the PI3K/AKT pathway and subsequently enhancing FoxO3a-mediated MnSOD expression.
TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription
Authors: Gómez-Herreros Fernando , Zagnoli-Vieira Guido , Ntai Ioanna , Martínez-Macías María Isabel , Anderson Rhona M. , Herrero-Ruíz Andrés , Caldecott Keith W. 
Published: August 2017

AbstractDNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.
Targeting the PI3K/Akt/mTOR signalling pathway in Cystic Fibrosis
Authors: Reilly R. , Mroz M. S. , Dempsey E. , Wynne K. , Keely S. J. , McKone E. F. , Hiebel C. , Behl C. , Coppinger J. A. 
Published: August 2017

AbstractDeletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (ΔF508 CFTR) is a major cause of cystic fibrosis (CF), one of the most common inherited childhood diseases. ΔF508 CFTR is a trafficking mutant that is retained in the endoplasmic reticulum (ER) and unable to reach the plasma membrane. Efforts to enhance exit of ΔF508 CFTR from the ER and improve its trafficking are of utmost importance for the development of treatment strategies. Using protein interaction profiling and global bioinformatics analysis we revealed mammalian target of rapamycin (mTOR) signalling components to be associated with ∆F508 CFTR. Our results demonstrated upregulated mTOR activity in ΔF508 CF bronchial epithelial (CFBE41o-) cells. Inhibition of the Phosphatidylinositol 3-kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) pathway with 6 different inhibitors demonstrated an increase in CFTR stability and expression. Mechanistically, we discovered the most effective inhibitor, MK-2206 exerted a rescue effect by restoring autophagy in ΔF508 CFBE41o- cells. We identified Bcl-2-associated athanogene 3 (BAG3), a regulator of autophagy and aggresome clearance to be a potential mechanistic target of MK-2206. These data further link the CFTR defect to autophagy deficiency and demonstrate the potential of the PI3K/Akt/mTOR pathway for therapeutic targeting in CF.
Host mechanisms involved in cattle Escherichia coli O157 shedding: a fundamental understanding for reducing foodborne pathogen in food animal production
Authors: Wang Ou , McAllister Tim A. , Plastow Graham , Stanford Kim , Selinger Brent , Guan Le Luo 
Published: August 2017

AbstractThe host mechanisms involved in Escherichia coli O157 super-shedding in cattle is largely unknown. In this study, the comparison of transcriptomes of intestinal tissues between super-shedders (SS) and cattle negative for E. coli O157 (NS) was performed, aiming to identify genes that are potentially associated with super-shedding. In total, 16,846 ± 639 (cecum) to 18,137 ± 696 (distal jejunum) were expressed throughout the intestine, with the expressed genes associated with immune functions more pronounced in the small intestine. In total, 351 differentially expressed (DE) genes were identified throughout the intestine between SS and NS, with 101 being up-regulated and 250 down-regulated in SS. Functional analysis revealed DE genes were involved in increased T-cell responses and cholesterol absorption in the distal jejunum and descending colon, and decreased B-cell maturation in the distal jejunum of SS. RNA-Seq based SNP discovery revealed that the mutations in seven DE genes involved in leukocyte activation and cholesterol transportation were associated with E. coli O157 shedding. Our findings suggest that T-cell responses and cholesterol metabolism in the intestinal tract may be associated with super-shedding phenomenon, and the SNPs in the DE genes are possibly associated with the observed gene expression difference between SS and NS.
High-resolution transport-of-intensity quantitative phase microscopy with annular illumination
Authors: Zuo Chao , Sun Jiasong , Li Jiaji , Zhang Jialin , Asundi Anand , Chen Qian 
Published: August 2017

AbstractFor quantitative phase imaging (QPI) based on transport-of-intensity equation (TIE), partially coherent illumination provides speckle-free imaging, compatibility with brightfield microscopy, and transverse resolution beyond coherent diffraction limit. Unfortunately, in a conventional microscope with circular illumination aperture, partial coherence tends to diminish the phase contrast, exacerbating the inherent noise-to-resolution tradeoff in TIE imaging, resulting in strong low-frequency artifacts and compromised imaging resolution. Here, we demonstrate how these issues can be effectively addressed by replacing the conventional circular illumination aperture with an annular one. The matched annular illumination not only strongly boosts the phase contrast for low spatial frequencies, but significantly improves the practical imaging resolution to near the incoherent diffraction limit. By incorporating high-numerical aperture (NA) illumination as well as high-NA objective, it is shown, for the first time, that TIE phase imaging can achieve a transverse resolution up to 208 nm, corresponding to an effective NA of 2.66. Time-lapse imaging of in vitro Hela cells revealing cellular morphology and subcellular dynamics during cells mitosis and apoptosis is exemplified. Given its capability for high-resolution QPI as well as the compatibility with widely available brightfield microscopy hardware, the proposed approach is expected to be adopted by the wider biology and medicine community.
TDP-43 stabilises the processing intermediates of mitochondrial transcripts
Authors: Izumikawa Keiichi , Nobe Yuko , Yoshikawa Harunori , Ishikawa Hideaki , Miura Yutaka , Nakayama Hiroshi , Nonaka Takashi , Hasegawa Masato , Egawa Naohiro , Inoue Haruhisa , Nishikawa Kouki , Yamano Koji , Simpson Richard J. , Taoka Masato , Yamauchi Yoshio , Isobe Toshiaki , Takahashi Nobuhiro 
Published: August 2017

AbstractThe 43-kDa trans-activating response region DNA-binding protein 43 (TDP-43) is a product of a causative gene for amyotrophic lateral sclerosis (ALS). Despite of accumulating evidence that mitochondrial dysfunction underlies the pathogenesis of TDP-43–related ALS, the roles of wild-type TDP-43 in mitochondria are unknown. Here, we show that the small TDP-43 population present in mitochondria binds directly to a subset of mitochondrial tRNAs and precursor RNA encoded in L-strand mtDNA. Upregulated expression of TDP-43 stabilised the processing intermediates of mitochondrial polycistronic transcripts and their products including the components of electron transport and 16S mt-rRNA, similar to the phenotype observed in cells deficient for mitochondrial RNase P. Conversely, TDP-43 deficiency reduced the population of processing intermediates and impaired mitochondrial function. We propose that TDP-43 has a novel role in maintaining mitochondrial homeostasis by regulating the processing of mitochondrial transcripts.
Neonatal leptin treatment reverses the bone-suppressive effects of maternal undernutrition in adult rat offspring
Authors: Firth Elwyn C. , Gamble Greg D. , Cornish Jillian , Vickers Mark H. 
Published: August 2017

AbstractAlterations in the early life environment, including maternal undernutrition (UN) during pregnancy, can lead to increased risk of metabolic and cardiovascular disorders in offspring. Leptin treatment of neonates born to UN rats reverses the programmed metabolic phenotype, but the possible benefits of this treatment on bone tissue have not been defined. We describe for the first time the effects of neonatal leptin treatment on bone in adult offspring following maternal UN. Offspring from either UN or ad libitum-fed (AD) rats were treated with either saline or leptin (2.5 µg/ g.d on postnatal days (D)3–13) and were fed either a chow or high fat (HF) diet from weaning until study completion at D170. Analysis of micro-tomographic data of the left femur showed highly significant effects of UN on cortical and trabecular bone tissue indices, contributing to inferior microstructure and bone strength, almost all of which were reversed by early leptin life treatment. The HF fat diet negatively affected trabecular bone tissue, but the effects of only trabecular separation and number were reversed by leptin treatment. The negative effects of maternal UN on skeletal health in adult offspring might be prevented or attenuated by various interventions including leptin. Establishment of a minimal efficacious leptin dose warrants further study.
The trophic role of a large marine predator, the tiger shark Galeocerdo cuvier
Authors: Ferreira Luciana C. , Thums Michele , Heithaus Michael R. , Barnett Adam , Abrantes Kátya G. , Holmes Bonnie J. , Zamora Lara M. , Frisch Ashley J. , Pepperell Julian G. , Burkholder Derek , Vaudo Jeremy , Nowicki Robert , Meeuwig Jessica , Meekan Mark G. 
Published: August 2017

AbstractTiger sharks were sampled off the western (Ningaloo Reef, Shark Bay) and eastern (the Great Barrier Reef; GBR, Queensland and New South Wales; NSW) coastlines of Australia. Multiple tissues were collected from each shark to investigate the effects of location, size and sex of sharks on δ13C and δ15N stable isotopes among these locations. Isotopic composition of sharks sampled in reef and seagrass habitats (Shark Bay, GBR) reflected seagrass-based food-webs, whereas at Ningaloo Reef analysis revealed a dietary transition between pelagic and seagrass food-webs. In temperate habitats off southern Queensland and NSW coasts, shark diets relied on pelagic food-webs. Tiger sharks occupied roles at the top of food-webs at Shark Bay and on the GBR, but not at Ningaloo Reef or off the coast of NSW. Composition of δ13C in tissues was influenced by body size and sex of sharks, in addition to residency and diet stability. This variability in stable isotopic composition of tissues is likely to be a result of adaptive foraging strategies that allow these sharks to exploit multiple shelf and offshore habitats. The trophic role of tiger sharks is therefore both context- and habitat-dependent, consistent with a generalist, opportunistic diet at the population level.
Information Security Scheme Based on Computational Temporal Ghost Imaging
Authors: Jiang Shan , Wang Yurong , Long Tao , Meng Xiangfeng , Yang Xiulun , Shu Rong , Sun Baoqing 
Published: August 2017

AbstractAn information security scheme based on computational temporal ghost imaging is proposed. A sequence of independent 2D random binary patterns are used as encryption key to multiply with the 1D data stream. The cipher text is obtained by summing the weighted encryption key. The decryption process can be realized by correlation measurement between the encrypted information and the encryption key. Due to the instinct high-level randomness of the key, the security of this method is greatly guaranteed. The feasibility of this method and robustness against both occlusion and additional noise attacks are discussed with simulation, respectively.
Proteomics/phosphoproteomics of left ventricular biopsies from patients with surgical coronary revascularization and pigs with coronary occlusion/reperfusion: remote ischemic preconditioning
Authors: Gedik Nilgün , Krüger Marcus , Thielmann Matthias , Kottenberg Eva , Skyschally Andreas , Frey Ulrich H. , Cario Elke , Peters Jürgen , Jakob Heinz , Heusch Gerd , Kleinbongard Petra 
Published: August 2017

AbstractRemote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion reduces myocardial ischemia/reperfusion injury. In left ventricular (LV) biopsies from patients undergoing coronary artery bypass grafting (CABG), only the activation of signal transducer and activator of transcription 5 was associated with RIPC’s cardioprotection. We have now used an unbiased, non-hypothesis-driven proteomics and phosphoproteomics approach to analyze LV biopsies from patients undergoing CABG and from pigs undergoing coronary occlusion/reperfusion without (sham) and with RIPC. False discovery rate-based statistics identified a higher prostaglandin reductase 2 expression at early reperfusion with RIPC than with sham in patients. In pigs, the phosphorylation of 116 proteins was different between baseline and early reperfusion with RIPC and/or with sham. The identified proteins were not identical for patients and pigs, but in-silico pathway analysis of proteins with ≥2-fold higher expression/phosphorylation at early reperfusion with RIPC in comparison to sham revealed a relation to mitochondria and cytoskeleton in both species. Apart from limitations of the proteomics analysis per se, the small cohorts, the sampling/sample processing and the number of uncharacterized/unverifiable porcine proteins may have contributed to this largely unsatisfactory result.
Characteristics of the mechanosensitive bladder afferent activities in relation with microcontractions in male rats with bladder outlet obstruction
Authors: Aizawa Naoki , Ichihara Koji , Fukuhara Hiroshi , Fujimura Tetsuya , Andersson Karl-Erik , Homma Yukio , Igawa Yasuhiko 
Published: August 2017

AbstractWe investigated the characteristics of bladder mechanosensitive single-unit afferent activities (SAAs) in rats with a bladder outlet obstruction (BOO) and their relationship with bladder microcontractions. Male Wistar rats were divided into Sham and BOO groups. Four or 10 days after the surgery, rats were anesthetized with urethane. The SAAs of Aδ- or C-fibers from the L6 dorsal roots were recorded during bladder filling. The BOO group showed a higher number of microcontractions and lower SAAs of Aδ-fibers compared with those of the Sham group. These findings were significant at day 10 post-operatively. In contrast, SAAs of C-fibers were not significantly different between the groups at either day 4 or 10. In the BOO group at day 10, the SAAs of both Aδ- and C-fibers at the “ascending” phase of microcontractions were significantly higher than those at the other phases (descending or stationary), and a similar tendency was also observed at day 4. Taken together, during bladder filling, the bladder mechanosensitive SAAs of Aδ-fibers were attenuated, but SAAs of both Aδ- and C-fibers were intermittently enhanced by propagation of microcontractions.
Genetic variation at the CD28 locus and its impact on expansion of pro-inflammatory CD28 negative T cells in healthy individuals
Authors: Liaskou Evaggelia , Jeffery Louisa , Chanouzas Dimitrios , Soskic Blagoje , Seldin Michael F. , Harper Lorraine , Sansom David , Hirschfield Gideon M. 
Published: August 2017

AbstractTheCD28locus is associated with susceptibility to a variety of autoimmune and immune-mediated inflammatory diseases including primary sclerosing cholangitis (PSC). Previously, we linked the CD28 pathway in PSC disease pathology and found that vitamin D could maintain CD28 expression. Here, we assessed whether the PSC-associatedCD28risk variant A (rs7426056) affects CD28 expression and T cell function in healthy individuals (n = 14 AA, n = 14 AG, n = 14 GG). Homozygotes for the PSC disease risk allele (AA) showed significantly lowerCD28mRNA expressionex-vivothan either GG or AG (p < 0.001) in total peripheral blood mononuclear cells. However, theCD28risk variant alone was not sufficient to explain CD28 protein loss on CD4+T cells. All genotypes responded equally to vitamin D as indicated by induction of a regulatory phenotype and an increased anti-inflammatory/pro-inflammatory cytokine ratio. A genotypic effect on response to TNFα stimuli was detected, which was inhibited by vitamin D. Together our results show: (a) an altered gene expression in carriers of the susceptible CD28 variant, (b) no differences in protein levels on CD4+T cells, and (c) a protective effect of the variant upon CD28 protein loss on CD4+T cells under inflammatory conditions.
Vitamin B12 as a carrier of peptide nucleic acid (PNA) into bacterial cells
Authors: Równicki Marcin , Wojciechowska Monika , Wierzba Aleksandra J. , Czarnecki Jakub , Bartosik Dariusz , Gryko Dorota , Trylska Joanna 
Published: August 2017

AbstractShort modified oligonucleotides targeted at bacterial DNA or RNA could serve as antibacterial agents provided that they are efficiently taken up by bacterial cells. However, the uptake of such oligonucleotides is hindered by the bacterial cell wall. To overcome this problem, oligomers have been attached to cell-penetrating peptides, but the efficiency of delivery remains poor. Thus, we have investigated the ability of vitamin B12 to transport peptide nucleic acid (PNA) oligomers into cells of Escherichia coli and Salmonella Typhimurium. Vitamin B12 was covalently linked to a PNA oligomer targeted at the mRNA of a reporter gene expressing Red Fluorescent Protein. Cu-catalyzed 1,3-dipolar cycloaddition was employed for the synthesis of PNA-vitamin B12 conjugates; namely the vitamin B12 azide was reacted with PNA possessing the terminal alkyne group. Different types of linkers and spacers between vitamin B12 and PNA were tested, including a disulfide bond. We found that vitamin B12 transports antisense PNA into E. coli cells more efficiently than the most widely used cell-penetrating peptide (KFF)3K. We also determined that the structure of the linker impacts the antisense effect. The results of this study provide the foundation for developing vitamin B12 as a carrier of PNA oligonucleotides into bacterial cells.
Hinge-initiated Primer-dependent Amplification of Nucleic Acids (HIP) – A New Versatile Isothermal Amplification Method
Authors: Fischbach Jens , Frohme Marcus , Glökler Jörn 
Published: August 2017

AbstractThe growing demand for cost-effective nucleic acid detection assays leads to an increasing number of different isothermal amplification reaction methods. However, all of the most efficient methods suffer from highly complex assay conditions due to the use of complicated primer sets and/or auxiliary enzymes. The present study describes the application of a new linker moiety that can be incorporated between a primer and a secondary target binding site which can act both as a block to polymerase extension as well as a hinge for refolding. This novel “hinge-primer” approach results in an efficient regeneration of the primer binding site and thus improves the strand-displacement and amplification process under isothermal conditions. Our investigations revealed that the reaction with forward and reverse hinge-primer including an abasic site is very efficient. The assay complexity can be reduced by combining the hinge-primer with a corresponding linear primer. Furthermore, the reaction speed can be increased by reducing the length of the amplified target sequence. We tested the sensitivity down to 104 copies and found a linear correlation between reaction time and input copy number. Our approach overcomes the usually cumbersome primer-design and extends the range of isothermal amplification methods using a polymerase with strand-displacement activity.
Unusual Inner-Salt Guaiazulene Alkaloids and bis-Sesquiterpene from the South China Sea Gorgonian Muriceides collaris
Authors: Li Pinglin , Liu Xiaoling , Zhu Hongyan , Tang Xuli , Shi Xuefeng , Liu Yonghong , Li Guoqiang 
Published: August 2017

AbstractThree new guaiazulene alkaloids muriceidines A–C (1–3) and one new bis-sesquiterpene muriceidone A (4), were isolated from the South China Sea gorgonian Muriceides collaris. Muriceidines are the first examples structurally architected by guaiazulene coupling with an inner-salt Δ1-pipecolic acid via a unique sp2 methine-bridged linkage, and the bis-sesquiterpene was comprised by a guaiazulene and a indene units linked through a unprecedented carbon-carbon σ-bond between the high steric bridgehead carbon C-10 of guaiazulene moiety and C-2′ of indene moiety. The chiral compounds 2–4 were obtained initially as racemates and further separated by chiral HPLC methods. The inner-salt structures of 1–3 and absolute configurations of 2–4 were fully elucidated by calculated 13C NMR, ECD and OR with quantum chemical calculation methods. Compound 1 showed cytotoxicity against K562 cell lines with IC50 value of 8.4 μM and antifouling activity against the larvae of the barnacle Balanus albicostatus with EC50 value of 11.9 μg/mL and potent therapeutic index (LC50/EC50 = 3.66). Also the racemic (±)-3 showed cytotoxicities against both HL-60 and K562 cell lines with IC50 values of 2.2 and 3.7 μM, respectively. A semisynthetic trial was performed to validate the proposed biosynthetic hypotheses.
A transcriptome atlas of rabbit revealed by PacBio single-molecule long-read sequencing
Authors: Chen Shi-Yi , Deng Feilong , Jia Xianbo , Li Cao , Lai Song-Jia 
Published: August 2017

AbstractIt is widely acknowledged that transcriptional diversity largely contributes to biological regulation in eukaryotes. Since the advent of second-generation sequencing technologies, a large number of RNA sequencing studies have considerably improved our understanding of transcriptome complexity. However, it still remains a huge challenge for obtaining full-length transcripts because of difficulties in the short read-based assembly. In the present study we employ PacBio single-molecule long-read sequencing technology for whole-transcriptome profiling in rabbit (Oryctolagus cuniculus). We totally obtain 36,186 high-confidence transcripts from 14,474 genic loci, among which more than 23% of genic loci and 66% of isoforms have not been annotated yet within the current reference genome. Furthermore, about 17% of transcripts are computationally revealed to be non-coding RNAs. Up to 24,797 alternative splicing (AS) and 11,184 alternative polyadenylation (APA) events are detected within this de novo constructed transcriptome, respectively. The results provide a comprehensive set of reference transcripts and hence contribute to the improved annotation of rabbit genome.