bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Holstein and Normande whole milk miRNomes highlights breed specificities
Authors: Le Guillou S. , Leduc A. , Laubier J. , Barbey S. , Rossignol M.-N. , Lefebvre R. , Marthey S. , Laloë D. , Le Provost F. 
Published: December 2019

AbstractThe concept of milk as a healthy food has opened the way for studies on milk components, from nutrients to microRNAs, molecules with broad regulatory properties present in large quantities in milk. Characterization of these components has been performed in several species, such as humans and bovine, depending on the stages of lactation. Here, we have studied the variation in milk microRNA composition according to genetic background. Using high throughput sequencing, we have characterized and compared the milk miRNomes of Holstein and Normande cattle, dairy breeds with distinct milk production features, in order to highlight microRNAs that are essential for regulation of the lactation process. In Holstein and Normande milk, 2,038 and 2,030 microRNAs were identified, respectively, with 1,771 common microRNAs, of which 1,049 were annotated and 722 were predicted. The comparison of the milk miRNomes of two breeds allowed to highlight 182 microRNAs displaying significant differences in the abundance. They are involved in the regulation of lipid metabolism and mammary morphogenesis and development, which affects lactation. Our results provide new insights into the regulation of molecular mechanisms involved in milk production.
IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C
Authors: Zhang Jian-fei , Tao Tao , Wang Kang , Zhang Guo-xiang , Yan Yujin , Lin Hui-ran , Li Yong , Guan Min-wu , Yu Jian-jun , Wang Xin-dong 
Published: December 2019

AbstractTenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.
Tuning PFKFB3 Bisphosphatase Activity Through Allosteric Interference
Authors: Macut Helena , Hu Xiao , Tarantino Delia , Gilardoni Ettore , Clerici Francesca , Regazzoni Luca , Contini Alessandro , Pellegrino Sara , Luisa Gelmi Maria 
Published: December 2019

AbstractThe human inducible phospho-fructokinase bisphosphatase isoform 3, PFKFB3, is a crucial regulatory node in the cellular metabolism. The enzyme is an important modulator regulating the intracellular fructose-2,6-bisphosphate level. PFKFB3 is a bifunctional enzyme with an exceptionally high kinase to phosphatase ratio around 740:1. Its kinase activity can be directly inhibited by small molecules acting directly on the kinase active site. On the other hand, here we propose an innovative and indirect strategy for the modulation of PFKFB3 activity, achieved through allosteric bisphosphatase activation. A library of small peptides targeting an allosteric site was discovered and synthesized. The binding affinity was evaluated by microscale thermophoresis (MST). Furthermore, a LC-MS/MS analytical method for assessing the bisphosphatase activity of PFKFB3 was developed. The new method was applied for measuring the activation on bisphosphatase activity with the PFKFB3-binding peptides. The molecular mechanical connection between the newly discovered allosteric site to the bisphosphatase activity was also investigated using both experimental and computational methods.
Switching of multi-state magnetic structures via domain wall propagation triggered by spin-orbit torques
Authors: Das Shubhankar , Zaig Ariel , Nhalil Hariharan , Avraham Liran , Schultz Moty , Klein Lior 
Published: December 2019

AbstractSpin-orbit torques emerge as a promising method for manipulating magnetic configurations of spintronic devices. Here, we show that these torques can induce a magnetization reversal via domain wall propagation which may open new ways in developing novel spintronic devices and in particular in realizing high-density multi-level magnetic memory. Our devices are bi-layer heterostructures of Ni0.8Fe0.2 on top of β-Ta patterned in the form of two or three crossing ellipses which exhibit in the crossing area shape-induced biaxial and triaxial magnetic anisotropy, respectively. We demonstrate field-free switching between discrete remanent magnetic states of the structures by spin-orbit torques induced by flowing electrical current through one of the ellipses. We note switchings induced by the coupling between the ellipses where current flowing in one ellipse triggers a reversal in a neighboring ellipse which propagates from the center outwards. Numerical tools successfully simulate the observed coupling-induced switching using experimentally extracted parameters.
Bivariate analysis of barley scald resistance with relative maturity reveals a new major QTL on chromosome 3H
Authors: Zhang Xuechen , Ovenden Ben , Orchard Beverley A. , Zhou Meixue , Park Robert F. , Singh Davinder , Milgate Andrew 
Published: December 2019

AbstractThe disease scald of barley is caused by the pathogen Rhynchosporium commune and can cause up to 30–40% yield loss in susceptible cultivars. In this study, the Australian barley cultivar ‘Yerong’ was demonstrated to have resistance that differed from Turk (Rrs1 (Rh3 type)) based on seedling tests with 11 R. commune isolates. A doubled haploid population with 177 lines derived from a cross between ‘Yerong’ and the susceptible Australian cultivar ‘Franklin’ was used to identify quantitative trait loci (QTL) for scald resistance. A QTL on chromosome 3H was identified with large effect, consistent with a major gene conferring scald resistance at the seedling stage. Under field conditions, a bivariate analysis was used to model scald percentage of infected leaf area and relative maturity, the residuals from the regression were used as our phenotype for QTL analysis. This analysis identified one major QTL on chromosome 3H, which mapped to the same position as the QTL at seedling stage. The identified QTL on 3H is proposed to be different from the Rrs1 on the basis of seedling resistance against different R. commune isolates and physical map position. This study increases the current understanding of scald resistance and identifies genetic material possessing QTLs useful for the marker-assisted selection of scald resistance in barley breeding programs.
Quantum process capability
Authors: Kuo Chung-Cheng , Chen Shih-Hsuan , Lee Wei-Ting , Chen Hung-Ming , Lu He , Li Che-Ming 
Published: December 2019

AbstractPhysical processes in the quantum regime possess non-classical properties of quantum mechanics. However, methods for quantitatively identifying such processes are still lacking. Accordingly, in this study, we develop a framework for characterizing and quantifying the ability of processes to cause quantum-mechanical effects on physical systems. We start by introducing a new concept, referred to as quantum process capability, to evaluate the effects of an experimental process upon a prescribed quantum specification. Various methods are then introduced for measuring such a capability. It is shown that the methods are adapted to quantum process tomography for implementation of process capability measure and applicable to all physical processes that can be described using the general theory of quantum operations. The utility of the proposed framework is demonstrated through several examples, including processes of entanglement, coherence, and superposition. The formalism proposed in this study provides a generic approach for the identification of dynamical processes in quantum mechanics and facilitates the general classification of quantum-information processing.
Molecular mechanisms underlying nuchal hump formation in dolphin cichlid, Cyrtocara moorii
Authors: Lecaudey Laurène Alicia , Sturmbauer Christian , Singh Pooja , Ahi Ehsan Pashay 
Published: December 2019

AbstractEast African cichlid fishes represent a model to tackle adaptive changes and their connection to rapid speciation and ecological distinction. In comparison to bony craniofacial tissues, adaptive morphogenesis of soft tissues has been rarely addressed, particularly at the molecular level. The nuchal hump in cichlids fishes is one such soft-tissue and exaggerated trait that is hypothesized to play an innovative role in the adaptive radiation of cichlids fishes. It has also evolved in parallel across lakes in East Africa and Central America. Using gene expression profiling, we identified and validated a set of genes involved in nuchal hump formation in the Lake Malawi dolphin cichlid,Cyrtocara moorii. In particular, we found genes differentially expressed in the nuchal hump, which are involved in controlling cell proliferation (btg3,fosl1aandpdgfrb), cell growth (dlk1), craniofacial morphogenesis (dlx5a,mycnandtcf12), as well as regulators of growth-related signals (dpt,pappaandsocs2). This is the first study to identify the set of genes associated with nuchal hump formation in cichlids. Given that the hump is a trait that evolved repeatedly in several African and American cichlid lineages, it would be interesting to see if the molecular pathways and genes triggering hump formation follow a common genetic track or if the trait evolved in parallel, with distinct mechanisms, in other cichlid adaptive radiations and even in other teleost fishes.
In silico definition of new ligninolytic peroxidase sub-classes in fungi and putative relation to fungal life style
Authors: Mathé Catherine , Fawal Nizar , Roux Christophe , Dunand Christophe 
Published: December 2019

AbstractLigninolytic peroxidases are microbial enzymes involved in depolymerisation of lignin, a plant cell wall polymer found in land plants. Among fungi, only Dikarya were found to degrade lignin. The increase of available fungal genomes allows performing an expert annotation of lignin-degrading peroxidase encoding sequences with a particular focus on Class II peroxidases (CII Prx). In addition to the previously described LiP, MnP and VP classes, based on sequence similarity, six new sub-classes have been defined: three found in plant pathogen ascomycetes and three in basidiomycetes. The presence of CII Prxs could be related to fungal life style. Typically, necrotrophic or hemibiotrophic fungi, either ascomycetes or basidiomycetes, possess CII Prxs while symbiotic, endophytic or biotrophic fungi do not. CII Prxs from ascomycetes are rarely subjected to duplications unlike those from basidiomycetes, which can form large recent duplicated families. Even if these CII Prxs classes form two well distinct clusters with divergent gene structures (intron numbers and positions), they share the same key catalytic residues suggesting that they evolved independently from similar ancestral sequences with few or no introns. The lack of CII Prxs encoding sequences in early diverging fungi, together with the absence of duplicated class I peroxidase (CcP) in fungi containing CII Prxs, suggests the potential emergence of an ancestral CII Prx sequence from the duplicated CcP after the separation between ascomycetes and basidiomycetes. As some ascomycetes and basidiomycetes did not possess CII Prx, late gene loss could have occurred.
Amyloidophilic Molecule Interactions on the Surface of Insulin Fibrils: Cooperative Binding and Fluorescence Quenching
Authors: Ziaunys Mantas , Mikalauskaite Kamile , Smirnovas Vytautas 
Published: December 2019

AbstractProtein aggregation into insoluble fibrillar aggregates is linked to several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease. Commonly used methods to study aggregation inhibition or fibril destabilization by potential drugs include spectroscopic measurements of amyloidophilic dye molecule fluorescence or absorbance changes. In this work we show the cross-interactions of five different dye molecules on the surface of insulin amyloid fibrils, resulting in cooperative binding and fluorescence quenching.
Water channel pore size determines exclusion properties but not solute selectivity
Authors: Kitchen Philip , Salman Mootaz M. , Pickel Simone U. , Jennings Jordan , Törnroth-Horsefield Susanna , Conner Matthew T. , Bill Roslyn M. , Conner Alex C. 
Published: December 2019

AbstractAquaporins (AQPs) are a ubiquitous family of transmembrane water channel proteins. A subgroup of AQP water channels also facilitates transmembrane diffusion of small, polar solutes. A constriction within the pore, the aromatic/arginine (ar/R) selectivity filter, is thought to control solute permeability: previous studies on single representative water channel proteins suggest narrow channels conduct water, whilst wider channels permit passage of solutes. To assess this model of selectivity, we used mutagenesis, permeability measurements and in silico comparisons of water-specific as well as glycerol-permeable human AQPs. Our studies show that single amino acid substitutions in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeability in an AQP-specific manner. Comparison between in silico-calculated channel cross-sectional areas and in vitro permeability measurements suggests that selectivity filter cross-sectional area predicts urea but not glycerol permeability. Our data show that substrate discrimination in water channels depends on a complex interplay between the solute, pore size, and polarity, and that using single water channel proteins as representative models has led to an underestimation of this complexity.
Characterization and engineering of broadly reactive monoclonal antibody against hepatitis B virus X protein that blocks its interaction with DDB1
Authors: Tao Shuai , Pan Shaokun , Gu Chenjian , Wei Lili , Kang Ning , Xie Youhua , Liu Jing 
Published: December 2019

AbstractHepatitis B virus (HBV) X protein (HBx) plays diverse roles in both viral life cycle and HBV-related carcinogenesis. Its interaction with DNA damage-binding protein 1 (DDB1) was shown to be essential for engendering cellular conditions favorable for optimal viral transcription and replication. Previously, we described a mouse monoclonal antibody against HBx (anti-HBx 2A7) recognizing HBx encoded by representative strains from 7 of 8 known HBV genotypes. In this work, we further characterized 2A7 in order to explore its potential usefulness in HBx-targeting applications. We demonstrated that 2A7 recognizes a linear epitope mapped to L89PKVLHKR96 on HBx, a segment that is highly conserved across genotypes and coincidentally overlaps with the DDB1-interacting segment. HBx-DDB1 binding could be inhibited by 2A7 in vitro, suggesting therapeutic potential. Nucleic acid and amino acid sequences of 2A7 were then obtained, which allowed construction of recombinant antibody and single chain variable fragments (scFv). 2A7-derived recombinant antibody and scFv recapitulate 2A7’s HBx-binding capacity and epitope specificity. We also reported preliminary results using cell-penetrating peptide for delivering 2A7 antibody across cell membrane to target intracellular HBx. Anti-HBx 2A7 and 2A7-derived scFv characterized here may give rise to novel HBx-targeting diagnostics and therapeutics for HBV- and HBx-related pathologies.
Levosimendan and systemic vascular resistance in cardiac surgery patients: a systematic review and meta-analysis
Authors: Terbeck Sandra , Heinisch Paul Philipp , Lenz Armando , Friess Jan-Oliver , Guensch Dominik , Carrel Thierry , Eberle Balthasar , Erdoes Gabor 
Published: December 2019

AbstractLevosimendan is a potent non-adrenergic inodilator agent. The net effect of hemodynamic changes may result in a hyperdynamic state with low systemic vascular resistance. We conducted a systematic review and meta-analysis assessing hemodynamics in cardiac surgery patients treated with levosimendan. English-language literature was searched systematically from 2006 until October 2018, including randomized controlled trials and case-matched or retrospective studies providing at least two sequentially measured hemodynamic variables in adult patients who underwent cardiac surgery with cardiopulmonary bypass and were treated with levosimendan in comparison to alternative drugs or devices. Cardiac index significantly increased in the levosimendan group by 0.74 (0.24 to 1.23) [standardized mean difference (95% CI); p = 0.003] from baseline to postoperative day (POD) 1, and by 0.75 (0.25 to 1.25; p = 0.003) from baseline to POD 7, when corrected for the standardized mean difference at baseline by a multivariate mixed effects meta-analysis model. With this correction for baseline differences, other hemodynamic variables including systemic vascular resistance did not significantly differ until POD 1 [−0.17 (−0.64 to 0.30), p = 0.48] and POD 7 [−0.13 (−0.61 to 0.34), p = 0.58] between the levosimendan and the comparator group. Levosimendan increases cardiac index in patients undergoing cardiac surgery. Although levosimendan has inodilator properties, this meta-analysis finds no clinical evidence that levosimendan produces vasopressor-resistant vasoplegic syndrome.
Adipose-derived Mesenchymal Stromal Cells Modulate Lipid Metabolism and Lipid Droplet Biogenesis via AKT/mTOR –PPARγ Signalling in Macrophages
Authors: Souza-Moreira Luciana , Soares Vinicius Cardoso , Dias Suelen da Silva Gomes , Bozza Patricia T. 
Published: December 2019

AbstractMesenchymal stromal cells (MSCs) are a potential therapy for many chronic inflammatory diseases due to their regenerative, immunologic and anti-inflammatory properties. The two-way dialogue between MSCs and macrophages is crucial to tissue regeneration and repair. Previous research demonstrated that murine adipose-derived MSC conditioned medium (ASCcm) reprograms macrophages to an M2-like phenotype which protects from experimental colitis and sepsis. Here, our focus was to determine the molecular mechanism of lipid droplet biogenesis in macrophages re-educated using ASCcm. Adipose-derived MSC conditioned medium promotes phosphorylation of AKT/mTOR pathway proteins in macrophages. Furthermore, increased expression of PPARγ, lipid droplet biogenesis and PGE2 synthesis were observed in M2-like phenotype macrophages (high expression of arginase 1 and elevated IL-10). Treatment with mTOR inhibitor rapamycin or PPARγ inhibitor GW9662 suppressed lipid droplets and PGE2 secretion. However, these inhibitors had no effect on arginase-1 expression. Rapamycin, but not GW9662, inhibit IL-10 secretion. In conclusion, we demonstrate major effects of ASCcm to reprogram macrophage immunometabolism through mTOR and PPARγ dependent and independent pathways.
Chaos theory discloses triggers and drivers of plankton dynamics in stable environment
Authors: Telesh Irena V. , Schubert Hendrik , Joehnk Klaus D. , Heerkloss Reinhard , Schumann Rhena , Feike Martin , Schoor Arne , Skarlato Sergei O. 
Published: December 2019

AbstractDespite the enticing discoveries of chaos in nature, triggers and drivers of this phenomenon remain a classical enigma which needs irrefutable empirical evidence. Here we analyze results of the yearlong replicated mesocosm experiment with multi-species plankton community that allowed revealing signs of chaos at different trophic levels in strictly controlled abiotic environment. In mesocosms without external stressors, we observed the “paradox of chaos” when biotic interactions (internal drivers) were acting as generators of internal abiotic triggers of complex plankton dynamics. Chaos was registered as episodes that vanished unpredictably or were substituted by complex behaviour of other candidates when longer time series were considered. Remarkably, episodes of chaos were detected even in the most abiotically stable conditions. We developed the Integral Chaos Indicator to validate the results of the Lyapunov exponent analysis. These findings are essential for modelling and forecasting behaviour of a variety of natural and other global systems.
Improving the practicality of using non-aversive handling methods to reduce background stress and anxiety in laboratory mice
Authors: Gouveia Kelly , Hurst Jane L. 
Published: December 2019

AbstractHandling can stimulate stress and anxiety in laboratory animals that negatively impacts welfare and introduces a confounding factor in many areas of research. Picking up mice by the tail is a major source of handling stress that results in strong aversion to the handler, while mice familiarised with being picked up in a tunnel or cupped on the open hand show low stress and anxiety, and actively seek interaction with their handlers. Here we investigate the duration and frequency of handling required for effective familiarisation with these non-aversive handling methods, and test whether this is sufficient to prevent aversion and anxiety when animals then experience immobilisation and a mild procedure (subcutaneous injection). Very brief handling (2 s) was sufficient to familiarise mice with tunnel handling, even when experienced only during cage cleaning. Brief but more frequent handling was needed for familiarisation with cup handling, while pick up by tail induced strong aversion even when handling was brief and infrequent. Experience of repeated immobilisation and subcutaneous injection did not reverse the positive effects of tunnel handling. Our findings demonstrate that replacing tail with tunnel handling during routine cage cleaning and procedures provides a major refinement with little if any cost for familiarisation.
Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas
Authors: Asano Naofumi , Takeshima Hideyuki , Yamashita Satoshi , Takamatsu Hironori , Hattori Naoko , Kubo Takashi , Yoshida Akihiko , Kobayashi Eisuke , Nakayama Robert , Matsumoto Morio , Nakamura Masaya , Ichikawa Hitoshi , Kawai Akira , Kondo Tadashi , Ushijima Toshikazu 
Published: December 2019

AbstractOsteosarcoma (OS) patients with metastasis or recurrent tumors still suffer from poor prognosis. Studies have indicated the efficacy of DNA demethylation therapy for OS, but the underlying mechanism is still unclear. Here, we aimed to clarify the mechanism of how epigenetic therapy has therapeutic efficacy in OS. Treatment of four OS cell lines with a DNA demethylating agent, 5-aza-2′-deoxycytidine (5-aza-dC) treatment, markedly suppressed their growth, and in vivo efficacy was further confirmed using two OS xenografts. Genome-wide DNA methylation analysis showed that 10 of 28 primary OS had large numbers of methylated CpG islands while the remaining 18 OS did not, clustering together with normal tissue samples and Ewing sarcoma samples. Among the genes aberrantly methylated in primary OS, genes involved in skeletal system morphogenesis were present. Searching for methylation-silenced genes by expression microarray screening of two OS cell lines after 5-aza-dC treatment revealed that multiple tumor-suppressor and osteo/chondrogenesis-related genes were re-activated by 5-aza-dC treatment of OS cells. Simultaneous activation of multiple genes related to osteogenesis and cell proliferation, namely epigenetic reprogramming, was considered to underlie the efficacy of DNA demethylation therapy in OS.