bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rsad2 is necessary for mouse dendritic cell maturation via the IRF7-mediated signaling pathway
Authors: Jang Ji-Su , Lee Jun-Ho , Jung Nam-Chul , Choi So-Yeon , Park Soo-Yeoun , Yoo Ji-Young , Song Jie-Young , Seo Han Geuk , Lee Hyun Soo , Lim Dae-Seog 
Published: August 2018

AbstractDendritic cells (DCs) are the most potent professional antigen presenting cells and inducers of T cell-mediated immunity. However, few specific markers of mature DCs (mDC) have been reported. A previous microarray analysis revealed expression of mDC-specific genes and identified Rsad2 (radical S-adenosyl methionine domain containing 2) as a candidate specific marker for DC maturation. Mouse bone marrow-derived DCs were transfected with Rsad2 siRNA and examined by flow cytometry, ELISA, western, and confocal microscopy. C57BL/6 mice received intravenously B16F10 cells to establish a pulmonary metastasis model. Tumor-bearing mice then received subcutaneously two injections of mDCs or Rsad2 knockdown DCs. The cytotoxic T lymphocyte (CTL) population was examined from splenocytes of DC-vaccinated mice by flow cytometry. Rsad2 was induced at high levels in LPS-stimulated mDCs and mDC function was markedly attenuated under conditions of Rsad2 knockdown. Moreover, Rsad2 was necessary for mDC maturation via the IRF7-mediated signaling pathway. The importance of Rsad2 was confirmed in an Rsad2 knockdown lung metastasis mouse model in which mDCs lost their antitumor efficacy. Data on the CTL population further supported the results as above. Taken together, Rsad2 was an obvious and specific marker necessary for DC maturation and these findings will be clearly helpful for further understanding of DC biology.
Deep learning to predict the lab-of-origin of engineered DNA
Authors: Nielsen Alec A. K. , Voigt Christopher A. 
Published: August 2018

AbstractGenetic engineering projects are rapidly growing in scale and complexity, driven by new tools to design and construct DNA. There is increasing concern that widened access to these technologies could lead to attempts to construct cells for malicious intent, illegal drug production, or to steal intellectual property. Determining the origin of a DNA sequence is difficult and time-consuming. Here deep learning is applied to predict the lab-of-origin of a DNA sequence. A convolutional neural network was trained on the Addgene plasmid dataset that contained 42,364 engineered DNA sequences from 2230 labs as of February 2016. The network correctly identifies the source lab 48% of the time and 70% it appears in the top 10 predicted labs. Often, there is not a single “smoking gun” that affiliates a DNA sequence with a lab. Rather, it is a combination of design choices that are individually common but collectively reveal the designer.
Strong whistler mode waves observed in the vicinity of Jupiter’s moons
Authors: Shprits Y. Y. , Menietti J. D. , Drozdov A. Y. , Horne R. B. , Woodfield E. E. , Groene J. B. , de Soria-Santacruz M. , Averkamp T. F. , Garrett H. , Paranicas C. , Gurnett D. A. 
Published: August 2018

AbstractUnderstanding of wave environments is critical for the understanding of how particles are accelerated and lost in space. This study shows that in the vicinity of Europa and Ganymede, that respectively have induced and internal magnetic fields, chorus wave power is significantly increased. The observed enhancements are persistent and exceed median values of wave activity by up to 6 orders of magnitude for Ganymede. Produced waves may have a pronounced effect on the acceleration and loss of particles in the Jovian magnetosphere and other astrophysical objects. The generated waves are capable of significantly modifying the energetic particle environment, accelerating particles to very high energies, or producing depletions in phase space density. Observations of Jupiter’s magnetosphere provide a unique opportunity to observe how objects with an internal magnetic field can interact with particles trapped in magnetic fields of larger scale objects.
Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding
Authors: Walters Lucy C. , Harlos Karl , Brackenridge Simon , Rozbesky Daniel , Barrett Jordan R. , Jain Vitul , Walter Thomas S. , O’Callaghan Chris A. , Borrow Persephone , Toebes Mireille , Hansen Scott G. , Sacha Jonah B , Abdulhaqq Shaheed , Greene Justin M. , Früh Klaus , Marshall Emily , Picker Louis J. , Jones E. Yvonne , McMichael Andrew J. , Gillespie Geraldine M. 
Published: August 2018

AbstractThrough major histocompatibility complex class Ia leader sequence-derived (VL9) peptide binding and CD94/NKG2 receptor engagement, human leucocyte antigen E (HLA-E) reports cellular health to NK cells. Previous studies demonstrated a strong bias for VL9 binding by HLA-E, a preference subsequently supported by structural analyses. However,Mycobacteria tuberculosis(Mtb) infection and Rhesus cytomegalovirus-vectored SIV vaccinations revealed contexts where HLA-E and the rhesus homologue, Mamu-E, presented diverse pathogen-derived peptides to CD8+T cells, respectively. Here we present crystal structures of HLA-E in complex with HIV and Mtb-derived peptides. We show that despite the presence of preferred primary anchor residues, HLA-E-bound peptides can adopt alternative conformations within the peptide binding groove. Furthermore, combined structural and mutagenesis analyses illustrate a greater tolerance for hydrophobic and polar residues in the primary pockets than previously appreciated. Finally, biochemical studies reveal HLA-E peptide binding and exchange characteristics with potential relevance to its alternative antigen presenting function in vivo.
Local orthorhombic lattice distortions in the paramagnetic tetragonal phase of superconducting NaFe1−xNixAs
Authors: Wang Weiyi , Song Yu , Cao Chongde , Tseng Kuo-Feng , Keller Thomas , Li Yu , Harriger L. W. , Tian Wei , Chi Songxue , Yu Rong , Nevidomskyy Andriy H. , Dai Pengcheng 
Published: August 2018

AbstractUnderstanding the interplay between nematicity, magnetism and superconductivity is pivotal for elucidating the physics of iron-based superconductors. Here we use neutron scattering to probe magnetic and nematic orders throughout the phase diagram of NaFe1−xNixAs, finding that while both static antiferromagnetic and nematic orders compete with superconductivity, the onset temperatures for these two orders remain well separated approaching the putative quantum critical points. We uncover local orthorhombic distortions that persist well above the tetragonal-to-orthorhombic structural transition temperature Ts in underdoped samples and extend well into the overdoped regime that exhibits neither magnetic nor structural phase transitions. These unexpected local orthorhombic distortions display Curie–Weiss temperature dependence and become suppressed below the superconducting transition temperature Tc, suggesting that they result from the large nematic susceptibility near optimal superconductivity. Our results account for observations of rotational symmetry breaking above Ts, and attest to the presence of significant nematic fluctuations near optimal superconductivity.
Regulation of striatal cells and goal-directed behavior by cerebellar outputs
Authors: Xiao Le , Bornmann Caroline , Hatstatt-Burklé Laetitia , Scheiffele Peter 
Published: August 2018

AbstractThe cerebellum integrates descending motor commands and sensory information to generate predictions and detect errors during ongoing behaviors. Cerebellar computation has been proposed to control motor but also non-motor behaviors, including reward expectation and cognitive flexibility. However, the organization and functional contribution of cerebellar output channels are incompletely understood. Here, we elaborate the cell-type specificity of a broad connectivity matrix from the deep cerebellar nuclei (DCN) to the dorsal striatum in mice. Cerebello-striatal connections arise from all deep cerebellar subnuclei and are relayed through intralaminar thalamic nuclei (ILN). In the dorsal striatum, these connections target medium spiny neurons, but also ChAT-positive interneurons, a class of tonically active interneurons implicated in shifting and updating behavioral strategies. Chemogenetic silencing of cerebello-striatal connectivity modifies function of striatal ChAT-positive interneurons. We propose that cerebello-striatal connections relay cerebellar computation to striatal circuits for goal-directed behaviors.
Precardiac organoids form two heart fields via Bmp/Wnt signaling
Authors: Andersen Peter , Tampakakis Emmanouil , Jimenez Dennisse V. , Kannan Suraj , Miyamoto Matthew , Shin Hye Kyung , Saberi Amir , Murphy Sean , Sulistio Edrick , Chelko Stephen P. , Kwon Chulan 
Published: August 2018

AbstractThe discovery of the first heart field (FHF) and the second heart field (SHF) led us to understand how cardiac lineages and structures arise during development. However, it remains unknown how they are specified. Here, we generate precardiac spheroids with pluripotent stem cells (PSCs) harboring GFP/RFP reporters under the control of FHF/SHF markers, respectively. GFP+ cells and RFP+ cells appear from two distinct areas and develop in a complementary fashion. Transcriptome analysis shows a high degree of similarities with embryonic FHF/SHF cells. Bmp and Wnt are among the most differentially regulated pathways, and gain- and loss-of-function studies reveal that Bmp specifies GFP+ cells and RFP+ cells via the Bmp/Smad pathway and Wnt signaling, respectively. FHF/SHF cells can be isolated without reporters by the surface protein Cxcr4. This study provides novel insights into understanding the specification of two cardiac origins, which can be leveraged for PSC-based modeling of heart field/chamber-specific disease.
Inhibition of a K9/K36 demethylase by an H3.3 point mutation found in paediatric glioblastoma
Authors: Voon Hsiao P. J. , Udugama Maheshi , Lin Wendi , Hii Linda , Law Ruby H.P. , Steer David L. , Das Partha P. , Mann Jeffrey R. , Wong Lee H. 
Published: August 2018

AbstractAn array of oncogenic histone point mutations have been identified across a number of different cancer studies. It has been suggested that some of these mutant histones can exert their effects by inhibiting epigenetic writers. Here, we report that the H3.3 G34R (glycine to arginine) substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induced chromatin alterations that were comparable to a KDM4 A/B/C triple-knockout. We find that H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity, demonstrating that histone mutations can act through inhibition of epigenetic erasers. These results suggest that histone point mutations can exert their effects through interactions with a range of epigenetic readers, writers and erasers.
Dietary stearic acid regulates mitochondria in vivo in humans
Authors: Senyilmaz-Tiebe Deniz , Pfaff Daniel H. , Virtue Sam , Schwarz Kathrin V. , Fleming Thomas , Altamura Sandro , Muckenthaler Martina U. , Okun Jürgen G. , Vidal-Puig Antonio , Nawroth Peter , Teleman Aurelio A. 
Published: August 2018

AbstractSince modern foods are unnaturally enriched in single metabolites, it is important to understand which metabolites are sensed by the human body and which are not. We previously showed that the fatty acid stearic acid (C18:0) signals via a dedicated pathway to regulate mitofusin activity and thereby mitochondrial morphology and function in cell culture. Whether this pathway is poised to sense changes in dietary intake of C18:0 in humans is not known. We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion. C18:0 intake also causes a drop in circulating long-chain acylcarnitines, suggesting increased fatty acid beta-oxidation in vivo. This work thereby identifies C18:0 as a dietary metabolite that is sensed by our bodies to control our mitochondria. This could explain part of the epidemiological differences between C16:0 and C18:0, whereby C16:0 increases cardiovascular and cancer risk whereas C18:0 decreases both.
Intrinsic processes drive variability in basal melting of the Totten Glacier Ice Shelf
Authors: Gwyther David E. , O’Kane Terence J. , Galton-Fenzi Benjamin K. , Monselesan Didier P. , Greenbaum Jamin S. 
Published: August 2018

AbstractOver the period 2003–2008, the Totten Ice Shelf (TIS) was shown to be rapidly thinning, likely due to basal melting. However, a recent study using a longer time series found high interannual variability present in TIS surface elevation without any apparent trend. Here we show that low-frequency intrinsic ocean variability potentially accounts for a large fraction of the variability in the basal melting of TIS. Specifically, numerical ocean model simulations show that up to 44% of the modelled variability in basal melting in the 1–5 year timescale (and up to 21% in the 5–10 year timescale) is intrinsic, with a similar response to the full climate forcing. We identify the important role of intrinsic ocean variability in setting the observed interannual variation in TIS surface thickness and velocity. Our results further demonstrate the need to account for intrinsic ocean processes in the detection and attribution of change.
Beam Steering Using Momentum-Reconfigurable Goubau Meta-Line Radiators
Authors: Tang Xiao-Lan , Zhang Qingfeng , Hu Sanming , Ge Shangkun , Chen Yifan , Yu Hao 
Published: August 2018

AbstractSpoof/designer surface plasmon polaritons (SPP) and Goubau line belong to the same category of single-conductor surface waveguide. They feature easy integration and high field confinement capability, and hence are good candidates for wave guiding and radiating at terahertz frequencies. Here, we propose a momentum-reconfigurable Goubau meta-line radiator that is capable of digitally steering its beam at a fixed frequency, in contrast to conventional SPP or Goubau line radiators relying on changing frequencies to steer beams. By periodically loading switchable meta-lines with ON and OFF states along the Goubau line, the modulation period and hence the momentum of Goubau line radiators can be dynamically controlled. The proposed Goubau line radiator is able to steer the main beam at a given frequency by independently switching ON or OFF each unit cell. As a proof of concept, we use line connection and disconnection to mimic ON and OFF state of the switch, respectively. Several radiators, representing different switching coding combinations, are fabricated and experimentally validated. Although this momentum-reconfigurable Goubau meta-line radiator is demonstrated at microwave frequency, it can be easily extended to terahertz frequencies.
An orally-active adiponectin receptor agonist mitigates cutaneous fibrosis, inflammation and microvascular pathology in a murine model of systemic sclerosis
Authors: Yamashita Takashi , Lakota Katja , Taniguchi Takashi , Yoshizaki Ayumi , Sato Shinichi , Hong Wen , Zhou Xingchun , Sodin-Semrl Snezn , Fang Feng , Asano Yoshihide , Varga John 
Published: August 2018

AbstractThe hallmarks of systemic sclerosis (SSc) are autoimmunity, microangiopathy and fibrosis. Skin fibrosis is accompanied by attrition of the dermal white adipose tissue layer, and alterations in the levels and function of adiponectin. Since these findings potentially implicate adiponectin in the pathogenesis of SSc, we employed a novel pharmacological approach to augment adiponectin signaling using AdipoRon, an orally active adiponectin receptor agonist. Chronic treatment with AdipoRon significantly ameliorated bleomycin-induced dermal fibrosis in mice. AdipoRon attenuated fibroblast activation, adipocyte-to-myofibroblast transdifferentiation, Th2/Th17-skewed polarization of the immune response, vascular injury and endothelial-to-mesenchymal transition within the lesional skin. In vitro, AdipoRon abrogated profibrotic responses elicited by TGF-β in normal fibroblasts, and reversed the inherently-activated profibrotic phenotype of SSc fibroblasts. In view of these broadly beneficial effects on all three cardinal pathomechanisms underlying the clinical manifestations of SSc, pharmacological augmentation of adiponectin signaling might represent a novel strategy for the treatment of SSc.
Use of the Extended Fujita method for representing the molecular weight and molecular weight distributions of native and processed oat beta-glucans
Authors: Channell Guy A. , Adams Gary G. , Lu YuDong , Gillis Richard B. , Dinu Vlad , Grundy Myriam M.-L. , Bajka Balazs , Butterworth Peter J. , Ellis Peter R. , Mackie Alan , Ballance Simon , Harding Stephen E. 
Published: August 2018

AbstractBeta 1–3, 1–4 glucans (“beta-glucans”) are one of the key components of the cell wall of cereals, complementing the main structural component cellulose. Beta-glucans are also an important source of soluble fibre in foods containing oats with claims of other beneficial nutritional properties such as plasma cholesterol lowering in humans. Key to the function of beta-glucans is their molecular weight and because of their high polydispersity - molecular weight distribution. Analytical ultracentrifugation provides a matrix-free approach (not requiring separation columns or media) to polymer molecular weight distribution determination. The sedimentation coefficient distribution is converted to a molecular weight distribution via a power law relation using an established procedure known as the Extended Fujita approach. We establish and apply the power law relation and Extended Fujita method for the first time to a series of native and processed oat beta-glucans. The application of this approach to beta-glucans from other sources is considered.
Oligomerization of bacterially expressed H1N1 recombinant hemagglutinin contributes to protection against viral challenge
Authors: Kuenstling Tess E. , Sambol Anthony R. , Hinrichs Steven H. , Larson Marilynn A. 
Published: August 2018

AbstractVaccination is the most effective intervention to prevent influenza and control the spread of the virus. Alternatives are needed to the traditional egg-based vaccine strategy for a more rapid response to new outbreaks. Two different hemagglutinin (HA) fragments (rHA11-326 and rHA153-269) derived from influenza A virus subtype H1N1 were expressed in Escherichia coli and characterized by immunoblot, gel filtration, hemagglutination, and competitive binding assays. rHA11-326 included neutralizing epitopes and the trimerization domain, whereas rHA153-269 included only the head of HA with the neutralizing epitopes. Mice were immunized with rHA11-326 or rHA153-269, and sera were tested for the presence of neutralizing antibodies. Mice were then challenged with H1N1 and infection severity was monitored. rHA11-326 trimerized, whereas rHA153-269 was unable to form oligomers. Both rHA11-326 and rHA153-269 elicited the production of neutralizing antibodies, but only oligomerized rHA11-326 protected against live virus challenges in mice. This study demonstrated that bacterially expressed HA was capable of folding properly and eliciting the production of neutralizing antibodies, and that HA oligomerization contributed to protection against viral challenge. Therefore, prokaryotic-derived vaccine platforms can provide antigenic and structural requirements for viral protection, as well as allow for the rapid and cost-effective incorporation of multiple antigens for broader protection.
Increased expression and altered localization of cathepsin Z are associated with progression to jaundice stage in primary biliary cholangitis
Authors: Aiba Yoshihiro , Harada Kenichi , Ito Masahiro , Suematsu Takashi , Aishima Shinichi , Hitomi Yuki , Nishida Nao , Kawashima Minae , Takatsuki Mitsuhisa , Eguchi Susumu , Shimoda Shinji , Nakamura Hitomi , Komori Atsumasa , Abiru Seigo , Nagaoka Shinya , Migita Kiyoshi , Yatsuhashi Hiroshi , Tokunaga Katsushi , Nakamura Minoru 
Published: August 2018

AbstractOur recent genome-wide association study found that the NELFCD/CTSZ locus was significantly associated with progression of primary biliary cholangitis (PBC) to jaundice stage in the Japanese population. In this study, we investigated the role of cathepsin Z in the etiology and pathology of PBC. Serum cathepsin Z levels were measured using enzyme-linked immunosorbent assay. The expression and localization of cathepsin Z in liver specimens were analyzed by western blotting and immunohistochemistry. In PBC patients, serum cathepsin Z levels were significantly increased with disease progression. In addition, its levels were positively correlated with alanine transaminase, aspartate transaminase and total bilirubin, and were negatively correlated with platelet count and albumin. Cathepsin Z expression was markedly increased in hepatocytes at later stages of PBC, and its localization was altered from the peri-bile canaliculus to the cytoplasm, where a fraction was no longer colocalized with endosomal/lysosomal vesicles. Similar altered expression of cathepsin Z was observed in end-stage of other cholestatic liver diseases including sepsis, obstructive jaundice, and Alagille syndrome. Our results indicate that altered expression and localization of cathepsin Z in hepatocytes are characteristic features of PBC and other cholestatic liver diseases, and are implicated in the progression of PBC.
Cooperative foraging expands dietary niche but does not offset intra-group competition for resources in social spiders
Authors: Majer Marija , Holm Christina , Lubin Yael , Bilde Trine 
Published: August 2018

AbstractGroup living animals invariably risk resource competition. Cooperation in foraging, however, may benefit individuals in groups by facilitating an increase in dietary niche. To test this, we performed a comparative study of social and solitary spider species. Three independently derived social species ofStegodyphus(Eresidae) occupy semi-arid savannas and overlap with three solitary congeners. We estimated potential prey availability in the environment and prey acquisition by spiders in their capture webs. We calculated dietary niche width (prey size) and breadth (taxonomic range) to compare resource use for these six species, and investigated the relationships between group size and average individual capture web production, prey biomass intake rate and variance in biomass intake. Cooperative foraging increased dietary niche width and breadth by foraging opportunistically, including both larger prey and a wider taxonomic range of prey in the diet. Individual capture web production decreased with increasing group size, indicating energetic benefits of cooperation, and variance in individual intake rate was reduced. However, individual biomass intake also decreased with increasing group size. While cooperative foraging did not completely offset resource competition among group members, it may contribute to sustaining larger groups by reducing costs of web production, increasing the dietary niche and reducing the variance in prey capture.