bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics
Authors: Akaike Takaaki , Ida Tomoaki , Wei Fan-Yan , Nishida Motohiro , Kumagai Yoshito , Alam Md. Morshedul , Ihara Hideshi , Sawa Tomohiro , Matsunaga Tetsuro , Kasamatsu Shingo , Nishimura Akiyuki , Morita Masanobu , Tomizawa Kazuhito , Nishimura Akira , Watanabe Satoshi , Inaba Kenji , Shima Hiroshi , Tanuma Nobuhiro , Jung Minkyung , Fujii Shigemoto , Watanabe Yasuo , Ohmuraya Masaki , Nagy Péter , Feelisch Martin , Fukuto Jon M. , Motohashi Hozumi 
Published: October 2017

AbstractCysteine hydropersulfide (CysSSH) occurs in abundant quantities in various organisms, yet little is known about its biosynthesis and physiological functions. Extensive persulfide formation is apparent in cysteine-containing proteins inEscherichia coliand mammalian cells and is believed to result from post-translational processes involving hydrogen sulfide-related chemistry. Here we demonstrate effective CysSSH synthesis from the substratel-cysteine, a reaction catalyzed by prokaryotic and mammalian cysteinyl-tRNA synthetases (CARSs). Targeted disruption of the genes encoding mitochondrial CARSs in mice and human cells shows that CARSs have a crucial role in endogenous CysSSH production and suggests that these enzymes serve as the principal cysteine persulfide synthases in vivo. CARSs also catalyze co-translational cysteine polysulfidation and are involved in the regulation of mitochondrial biogenesis and bioenergetics. Investigating CARS-dependent persulfide production may thus clarify aberrant redox signaling in physiological and pathophysiological conditions, and suggest therapeutic targets based on oxidative stress and mitochondrial dysfunction.
Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs
Authors: Syed Mansoor , Das Pragnya , Pawar Aishwarya , Aghai Zubair H. , Kaskinen Anu , Zhuang Zhen W. , Ambalavanan Namasivayam , Pryhuber Gloria , Andersson Sture , Bhandari Vineet 
Published: October 2017

AbstractHyperoxia-induced acute lung injury (HALI) is a key contributor to the pathogenesis of bronchopulmonary dysplasia (BPD) in neonates, for which no specific preventive or therapeutic agent is available. Here we show that lung micro-RNA (miR)-34a levels are significantly increased in lungs of neonatal mice exposed to hyperoxia. Deletion or inhibition of miR-34a improves the pulmonary phenotype and BPD-associated pulmonary arterial hypertension (PAH) in BPD mouse models, which, conversely, is worsened by miR-34a overexpression. Administration of angiopoietin-1, which is one of the downstream targets of miR34a, is able to ameliorate the BPD pulmonary and PAH phenotypes. Using three independent cohorts of human samples, we show that miR-34a expression is increased in type 2 alveolar epithelial cells in neonates with respiratory distress syndrome and BPD. Our data suggest that pharmacologic miR-34a inhibition may be a therapeutic option to prevent or ameliorate HALI/BPD in neonates.
A community effort to protect genomic data sharing, collaboration and outsourcing
Authors: Wang Shuang , Jiang Xiaoqian , Tang Haixu , Wang Xiaofeng , Bu Diyue , Carey Knox , Dyke Stephanie OM , Fox Dov , Jiang Chao , Lauter Kristin , Malin Bradley , Sofia Heidi , Telenti Amalio , Wang Lei , Wang Wenhao , Ohno-Machado Lucila 
Published: October 2017

AbstractThe human genome can reveal sensitive information and is potentially re-identifiable, which raises privacy and security concerns about sharing such data on wide scales. In 2016, we organized the third Critical Assessment of Data Privacy and Protection competition as a community effort to bring together biomedical informaticists, computer privacy and security researchers, and scholars in ethical, legal, and social implications (ELSI) to assess the latest advances on privacy-preserving techniques for protecting human genomic data. Teams were asked to develop novel protection methods for emerging genome privacy challenges in three scenarios: Track (1) data sharing through the Beacon service of the Global Alliance for Genomics and Health. Track (2) collaborative discovery of similar genomes between two institutions; and Track (3) data outsourcing to public cloud services. The latter two tracks represent continuing themes from our 2015 competition, while the former was new and a response to a recently established vulnerability. The winning strategy for Track 1 mitigated the privacy risk by hiding approximately 11% of the variation in the database while permitting around 160,000 queries, a significant improvement over the baseline. The winning strategies in Tracks 2 and 3 showed significant progress over the previous competition by achieving multiple orders of magnitude performance improvement in terms of computational runtime and memory requirements. The outcomes suggest that applying highly optimized privacy-preserving and secure computation techniques to safeguard genomic data sharing and analysis is useful. However, the results also indicate that further efforts are needed to refine these techniques into practical solutions.
Prediction of Indian Summer-Monsoon Onset Variability: A Season in Advance
Authors: Pradhan Maheswar , Rao A. Suryachandra , Srivastava Ankur , Dakate Ashish , Salunke Kiran , Shameera K. S. 
Published: October 2017

AbstractMonsoon onset is an inherent transient phenomenon of Indian Summer Monsoon and it was never envisaged that this transience can be predicted at long lead times. Though onset is precipitous, its variability exhibits strong teleconnections with large scale forcing such as ENSO and IOD and hence may be predictable. Despite of the tremendous skill achieved by the state-of-the-art models in predicting such large scale processes, the prediction of monsoon onset variability by the models is still limited to just 2–3 weeks in advance. Using an objective definition of onset in a global coupled ocean-atmosphere model, it is shown that the skillful prediction of onset variability is feasible under seasonal prediction framework. The better representations/simulations of not only the large scale processes but also the synoptic and intraseasonal features during the evolution of monsoon onset are the comprehensions behind skillful simulation of monsoon onset variability. The changes observed in convection, tropospheric circulation and moisture availability prior to and after the onset are evidenced in model simulations, which resulted in high hit rate of early/delay in monsoon onset in the high resolution model.
A proteome view of structural, functional, and taxonomic characteristics of major protein domain clusters
Authors: Sun Chia-Tsen , Chiang Austin W. T. , Hwang Ming-Jing 
Published: October 2017

AbstractProteome-scale bioinformatics research is increasingly conducted as the number of completely sequenced genomes increases, but analysis of protein domains (PDs) usually relies on similarity in their amino acid sequences and/or three-dimensional structures. Here, we present results from a bi-clustering analysis on presence/absence data for 6,580 unique PDs in 2,134 species with a sequenced genome, thus covering a complete set of proteins, for the three superkingdoms of life, Bacteria, Archaea, and Eukarya. Our analysis revealed eight distinctive PD clusters, which, following an analysis of enrichment of Gene Ontology functions and CATH classification of protein structures, were shown to exhibit structural and functional properties that are taxa-characteristic. For examples, the largest cluster is ubiquitous in all three superkingdoms, constituting a set of 1,472 persistent domains created early in evolution and retained in living organisms and characterized by basic cellular functions and ancient structural architectures, while an Archaea and Eukarya bi-superkingdom cluster suggests its PDs may have existed in the ancestor of the two superkingdoms, and others are single superkingdom- or taxa (e.g. Fungi)-specific. These results contribute to increase our appreciation of PD diversity and our knowledge of how PDs are used in species, yielding implications on species evolution.
Anatomical Study of the Neurovascular in Flexor Hallucis Longus Tendon Transfers
Authors: Mao Haijiao , Dong Wenwei , Shi Zengyuan , Yin Weigang , Xu Dachuan , Wapner Keith L. 
Published: October 2017

AbstractThe transfer of the flexor hallucis longus tendon or flexor digitorum longus tendon is frequently used for the treatment of posterior tibial tendon insufficiency or chronic Achilles tendinopathy. According to several anatomical studies, harvesting the flexor hallucis longus (FHL) tendon may cause nerve injury. Sixty-eight embalmed feet were dissected and anatomically classified to define the relationship between Henry’s knot and the plantar nerves. Two different configurations were identified. In Pattern 1, which was observed in 64 specimens (94.1%), the distance between the medial plantar nerve and Henry’s knot was 5.96 mm (range, 3.34 to 7.84, SD = 1.12). In Pattern 2, which was observed in 4 specimens (5.9%), there was no distance between the medial plantar nerve (MPN) and Henry’s knot. No statistically significant difference was observed according to gender or side (p > 0.05). A retraction was performed to harvest the FHL through the posteromedial hindfoot incision using a single minimally invasive technique, and the medial and lateral plantar nerve lesions were scrupulously assessed. In conclusion, medial and lateral plantar nerve injuries did not occur more frequently, even after performing a single minimally invasive incision to harvest the FHL tendon, due to the large distance between the FHL tendon and the medial and lateral plantar nerves.
Comparison of DGT with traditional methods for assessing cadmium bioavailability to Brassica chinensis in different soils
Authors: Dai Yunchao , Nasir Mubasher , Zhang Yulin , Wu Haiming , Guo Honghong , Lv Jialong 
Published: October 2017

AbstractThere is no universally accepted method for evaluating cadmium (Cd) bioavailability in soil. The diffusive gradient in thin films (DGT) technique is a promising tool, but there is considerable debate about its suitability. The ability of this technique to estimate Cd bioavailability in soils was compared with the abilities of other traditional chemical extraction techniques (soil solution, ethylene diamine tetraacetic acid (EDTA), acetic acid (HAc), calcium chloride (CaCl2), and pseudo-total Cd methods) based on a greenhouse experiment using pakchoi (Brassica chinensis) grown in 15 soils from different provinces of China. In addition, we assessed whether these methods were independent of the soil properties. Correlations between the plant and soil Cd concentrations measured with the traditional extraction techniques were dependent on the pH and organic carbon (OC) content, indicating that these methods are influenced by the soil properties. In contrast, the DGT measurements were independent of the soil properties and showed a higher correlation coefficient compared to that of the traditional techniques. Hence, the DGT technique is better and should be preferable for assessing Cd biological effectiveness in different soil types.
Emergence of early alterations in network oscillations and functional connectivity in a tau seeding mouse model of Alzheimer’s disease pathology
Authors: Ahnaou A. , Moechars D. , Raeymaekers L. , Biermans R. , Manyakov N. V. , Bottelbergs A. , Wintmolders C. , Van Kolen K. , Van De Casteele T. , Kemp J. A. , Drinkenburg W. H. 
Published: October 2017

AbstractSynaptic dysfunction and disconnectivity are core deficits in Alzheimer’s disease (AD), preceding clear changes in histopathology and cognitive functioning. Here, the early and late effects of tau pathology induction on functional network connectivity were investigated in P301L mice. Multichannel EEG oscillations were used to compute (1) coherent activity between the prefrontal cortex (PFC) and hippocampus (HPC) CA1-CA3 networks; (2) phase-amplitude cross frequency coupling (PAC) between theta and gamma oscillations, which is instrumental in adequate cognitive functioning; (3) information processing as assessed by auditory evoked potentials and oscillations in the passive oddball mismatch negativity-like (MMN) paradigm. At the end, the density of tau aggregation and GABA parvalbumin (PV+) interneurons were quantified by immunohistochemistry. Early weakening of EEG theta oscillations and coherent activity were revealed between the PFC and HPC CA1 and drastic impairments in theta–gamma oscillations PAC from week 2 onwards, while PV+ interneurons count was not altered. Moreover, the tau pathology disrupted the MMN complex amplitude and evoked gamma oscillations to standard and deviant stimuli suggesting altered memory formation and recall. The induction of intracellular tau aggregation by tau seed injection results in early altered connectivity and strong theta–gamma oscillations uncoupling, which may be exploited as an early electrophysiological signature of dysfunctional neuronal networks.
Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells
Authors: Cerino Giulia , Gaudiello Emanuele , Muraro Manuele Giuseppe , Eckstein Friedrich , Martin Ivan , Scherberich Arnaud , Marsano Anna 
Published: October 2017

AbstractIn vitrorecapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds. Perfusion culture of SVF-cells reproducibly promotedin vitrothe early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Compared to static cultures, perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells uponin vivoectopic implantation. This was likely mediated by pericytes, whose number was significantly higher (4.5-fold) under perfusion and whose targeted depletion resulted in lower efficiency of vascularization, with an increased host foreign body reaction. 3D-perfusion culture of SVF-cells leads to the engineering of a specialized milieu, here defined as anangiogenic niche. This system could serve as a model to investigate multi-cellular interactions in angiogenesis, and as a module supporting increased grafted cell survival in regenerative medicine.
Small Molecule Accurate Recognition Technology (SMART) to Enhance Natural Products Research
Authors: Zhang Chen , Idelbayev Yerlan , Roberts Nicholas , Tao Yiwen , Nannapaneni Yashwanth , Duggan Brendan M. , Min Jie , Lin Eugene C. , Gerwick Erik C. , Cottrell Garrison W. , Gerwick William H. 
Published: October 2017

AbstractVarious algorithms comparing 2D NMR spectra have been explored for their ability to dereplicate natural products as well as determine molecular structures. However, spectroscopic artefacts, solvent effects, and the interactive effect of functional group(s) on chemical shifts combine to hinder their effectiveness. Here, we leveraged Non-Uniform Sampling (NUS) 2D NMR techniques and deep Convolutional Neural Networks (CNNs) to create a tool, SMART, that can assist in natural products discovery efforts. First, an NUS heteronuclear single quantum coherence (HSQC) NMR pulse sequence was adapted to a state-of-the-art nuclear magnetic resonance (NMR) instrument, and data reconstruction methods were optimized, and second, a deep CNN with contrastive loss was trained on a database containing over 2,054 HSQC spectra as the training set. To demonstrate the utility of SMART, several newly isolated compounds were automatically located with their known analogues in the embedded clustering space, thereby streamlining the discovery pipeline for new natural products.
Therapeutic efficacy of a combined sage and bitter apple phytopharmaceutical in chronic DSS-induced colitis
Authors: Hoffmann Maximilian , Schwertassek Ulla , Seydel Aleksandra , Weber Klaus , Hauschildt Sunna , Lehmann Jörg 
Published: October 2017

AbstractInflammatory bowel diseases are multifactorial disorders of the gastrointestinal tract with rising incidence worldwide. Current standard therapies are only partially effective and often show severe adverse effects. Thus, novel, more efficient and well-tolerated therapeutic options are urgently needed. We have studied the therapeutic potential of a phytopharmaceutical combining sage and bitter apple (SBA) in the mouse model of chronic dextran sulfate sodium (DSS) colitis. SBA represents a traditional medicine against diarrhea and was shown to exhibit anti-inflammatory effects in vitro. In the chronic DSS colitis model SBA treatment significantly reduced clinical symptoms in a dose-dependent manner. The positive therapeutic effect of SBA was characterized by a decreased histopathological score indicating tissue healing. Moreover, the number of neutrophils as well as the expression of the neutrophil-recruiting chemokine CXCL-1/KC in the colon tissue was significantly reduced, whereas the recruitment of macrophages was induced. Also, the expression of inflammatory markers was significantly suppressed, while the expression of the anti-inflammatory cytokine interleukin-10 was induced in colon tissue following treatment with SBA. Phytopharmaceuticals are increasingly recognized as potential therapeutics in IBD. Thus, based on the results from this study, SBA can be considered as an alternative or supplementary option for IBD therapy.
The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation
Authors: Chiu Joy E. , Thekkiniath Jose , Choi Jae-Yeon , Perrin Benjamin A. , Lawres Lauren , Plummer Mark , Virji Azan Z. , Abraham Amanah , Toh Justin Y. , Zandt Michael Van , Aly Ahmed S. I. , Voelker Dennis R. , Mamoun Choukri Ben 
Published: October 2017

AbstractThe biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for survival ofPlasmodium falciparumwithin human erythrocytes. Accordingly, a PA analog α-PanAm showed potent activity against blood stage parasitesin vitro; however, its efficacyin vivoand its mode of action remain unknown. We developed a new synthesis route for α-PanAm and showed that the compound is highly effective against blood stages of drug-sensitive and -resistantP. falciparumstrains, inhibits development ofP. bergheiin hepatocytes, and at doses up to 100 mg/kg also inhibits blood stage development ofP. chabaudiin mice. We used yeast and its pantothenate kinase Cab1 as models to characterize mode of action of α-PanAm and found that α-PanAm inhibits yeast growth in a PA-dependent manner, and its potency increases dramatically in a yeast mutant with defective pantothenate kinase activity. Biochemical analyses using14C-PA as a substrate demonstrated that α-PanAm is a competitive inhibitor of Cab1. Interestingly, biochemical and mass spectrometry analyses also showed that the compound is phosphorylated by Cab1. Together, these data suggest that α-PanAm exerts its antimicrobial activity by direct competition with the natural substrate PA for phosphorylation by the pantothenate kinase.
Exopolysaccharides from Lactobacillus plantarum NCU116 induce c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in mouse intestinal epithelial cancer cells
Authors: Zhou Xingtao , Hong Tao , Yu Qiang , Nie Shaoping , Gong Deming , Xiong Tao , Xie Mingyong 
Published: October 2017

AbstractExopolysaccharides (EPS) from lactic acid bacteria (LAB) have been reported to play vital parts in the modulation of cell-cycle and apoptosis in cancer cells. However, the mechanisms by which EPS regulate the proliferation and apoptosis of cancer cells remain incompletely understood. We thus used different cancer cells to evaluate the anticancer ability and to investigate the underlying molecular mechanism of EPS from Lactobacillus plantarum NCU116 (EPS116). Our studies showed that EPS116 inhibited the proliferation of cancer cells in a cell type manner, and remarkably repressed the growth and survival of CT26 through induction of apoptosis. Moreover, EPS116 increased the expression of pro-apoptotic genes, including Fas, Fasl and c-Jun, induced the phosphorylation of c-Jun in CT26 cells. Furthermore, TLR2 (Toll like receptor 2) was upregulated by EPS116, and the CT26 cells with TLR2 knockdown were found to be insensitive to EPS116, suggesting that the anti-cancer activity of EPS116 may be TLR2-dependent. Taken together, the suppressive efficacy of EPS116 on the proliferation of CT26 cells may be mediated via TLR2 and the activation of c-Jun dependent Fas/Fasl-mediated apoptotic pathway. Our study has, for the first time, shown that EPS from LAB induced c-Jun dependent Fas/Fasl-mediated apoptosis via TLR2 in CT26 cells.
Ca2+ protein alpha 1D of CaV1.3 regulates intracellular calcium concentration and migration of colon cancer cells through a non-canonical activity
Authors: Fourbon Yann , Guéguinou Maxime , Félix Romain , Constantin Bruno , Uguen Arnaud , Fromont Gaëlle , Lajoie Laurie , Magaud Christophe , Lecomte Thierry , Chamorey Emmanuel , Chatelier Aurélien , Mignen Olivier , Potier-Cartereau Marie , Chantôme Aurélie , Bois Patrick , Vandier Christophe 
Published: October 2017

AbstractIt is generally accepted that voltage-gated Ca2+ channels, CaV, regulate Ca2+ homeostasis in excitable cells following plasma membrane depolarization. Here, we show that the Ca2+ protein α1D of CaV1.3 channel is overexpressed in colorectal cancer biopsies compared to normal tissues. Gene silencing experiments targeting α1D reduced the migration and the basal cytosolic Ca2+ concentration of HCT116 colon cancer cell line and modified the cytosolic Ca2+ oscillations induced by the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly, NCX1/3 regulated membrane potential of HCT116 cells only when α1D was silenced, and blocking NCX1/3 increased cytosolic Ca2+ concentration and cell migration. However, membrane depolarization did not induce an increase in intracellular Ca2+. Patch-clamp experiments clearly showed that the inward Ca2+ current was absent. Finally, flow cytometry and immunofluorescence studies showed that α1D protein was localized at the plasma membrane, in cytosol and cell nuclei. Altogether, we uncover a novel signaling pathway showing that α1D is involved in the regulation of Ca2+ homeostasis and cell migration by a mechanism independent of its plasma membrane canonical function but that involved plasma membrane Na+/Ca2+ exchanger.
Gap enhanced fluorescence as a road map for the detection of very weakly fluorescent emitters from visible to ultraviolet
Authors: McArthur Duncan , Papoff Francesco 
Published: October 2017

AbstractWe analyze the enhancement of the rates of both the emission and the far field radiation for dipoles placed in the gap between a metallic nanorod, or nanosphere, and a metallic substrate. For wavelengths between 150 nm and 650 nm, the response of the gapped nanostructures considered in this work is dominated by few principal modes of the nanoparticle, which include self-consistently the effect of the substrate. For wavelengths shorter than 370 nm, the far field radiative enhancements of aluminum nanostructures are significantly higher than those for gold or silver. With aluminum, bright mode resonances are tunable over tens or hundreds of nanometers by changing the size of the nanoparticle and have far field radiative enhancements of up to three orders of magnitude. These results provide a road map to label-free detection of many emitters too weakly fluorescent for present approaches.