bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graft-Versus-Host Disease Amelioration by Human Bone Marrow Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles Is Associated with Peripheral Preservation of Naive T Cell Populations
Authors: Fujii Sumie , Miura Yasuo , Fujishiro Aya , Shindo Takero , Shimazu Yutaka , Hirai Hideyo , Tahara Hidetoshi , Takaori-Kondo Akifumi , Ichinohe Tatsuo , Maekawa Taira 
Published: December 2017

Abstract
A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs. In EV-treated GVHD mice, CD4+ and CD8+ T cells were suppressed. Importantly, the ratio of CD62L-CD44+ to CD62L + CD44- T cells was decreased, suggesting that BM-MSC-derived EVs suppressed the functional differentiation of T cells from a naive to an effector phenotype. BM-MSC-derived EVs also preserved CD4 + CD25 + Foxp3+ regulatory T cell populations. In a culture of CD3/CD28-stimulated human peripheral blood mononuclear cells with BM-MSC-derived EVs, CD3+ T cell activation was suppressed. However, these cells were not suppressed in cultures with EVs derived from normal human dermal fibroblasts (NHDFs). NHDF-derived EVs did not ameliorate the clinical or pathological characteristics of aGVHD in mice, suggesting an immunoregulatory function unique to BM-MSC-derived EVs. Microarray analysis of microRNAs in BM-MSC-derived EVs versus NHDF-derived EVs showed upregulation of miR-125a-3p and downregulation of cell proliferative processes, as identified by Gene Ontology enrichment analysis. Collectively, our findings provide the first evidence that amelioration of aGVHD by therapeutic infusion of BM-MSC-derived EVs is associated with the preservation of circulating naive T cells, possibly due to the unique microRNA profiles of BM-MSC-derived EVs.
Cover Image, Volume 10, Issue 1
Authors: Tian Xin , Zhang Lechuan , Yang Mo , Bai Lei , Dai Yiheng , Yu Zhiqiang , Pan Yue 
Published: December 2017

The cover image, by Xin Tian et al., is based on the Focus Article Functional magnetic hybrid nanomaterials for biomedical diagnosis and treatment, DOI: 10.1002/wnan.1476.
image
A Psychometric Analysis of the Student Version of the Perceptions of	Inclusion Questionnaire (PIQ)
Authors: Zurbriggen Carmen L. A. , Venetz Martin , Schwab Susanne , Hessels Marco G. P. 
Published: December 2017

Abstract. The German version of the Perception of Inclusion Questionnaire (PIQ), which is used to assess students’ emotional inclusion, social inclusion, and academic self-concept, was analyzed with the multi-unidimensional graded response model (GRM) and investigated for differential item functioning (DIF) between students with and without learning difficulties (LD). The PIQ was administered to 823 primary school students in Switzerland ( Mage = 11.94, SD = 1.01 years), of which 190 were classified as having LD. Results show that the PIQ is a reliable instrument for assessing students’ perceptions of their inclusion at school, especially in the lower ranges of the scales. No bias was detected for any items of the PIQ’s three scales in relation to the exogenous variable LD, with the exception of one item that showed a minor deviation.
Unforeseen swimming and gliding mode of an insect gut symbiont, Burkholderia sp. RPE64, with wrapping of the flagella around its cell body
Authors: Kinosita Yoshiaki , Kikuchi Yoshitomo , Mikami Nagisa , Nakane Daisuke , Nishizaka Takayuki 
Published: December 2017

Abstract
A bean bug symbiont, Burkholderia sp. RPE64, selectively colonizes the gut crypts by flagella-mediated motility: however, the mechanism for this colonization remains unclear. Here, to obtain clues to this mechanism, we characterized the swimming motility of the Burkholderia symbiont under an advanced optical microscope. High-speed imaging of cells enabled the detection of turn events with up to 5-ms temporal resolution, indicating that cells showed reversal motions (θ ~ 180°) with rapid changes in speed by a factor of 3.6. Remarkably, staining of the flagellar filaments with a fluorescent dye Cy3 revealed that the flagellar filaments wrap around the cell body with a motion like that of a ribbon streamer in rhythmic gymnastics. A motility assay with total internal reflection fluorescence microscopy revealed that the left-handed flagellum wound around the cell body and propelled it forward by its clockwise rotation. We also detected periodic-fluorescent signals of flagella on the glass surface, suggesting that flagella possibly contacted the solid surface directly and produced a gliding-like motion driven by flagellar rotation. Finally, the wrapping motion was also observed in a symbiotic bacterium of the bobtail squid, Aliivibrio fischeri, suggesting that this motility mode may contribute to migration on the mucus-filled narrow passage connecting to the symbiotic organ.
Schizophrenia-risk and urban birth are associated with proteomic changes in neonatal dried blood spots
Authors: Cooper Jason D. , Ozcan Sureyya , Gardner Renee M. , Rustogi Nitin , Wicks Susanne , van Rees Geertje F. , Leweke F. Markus , Dalman Christina , Karlsson Håkan , Bahn Sabine 
Published: December 2017

AbstractIn the present study, we tested whether there were proteomic differences in blood between schizophrenia patients after the initial onset of the disorder and controls; and whether those differences were also present at birth among neonates who later developed schizophrenia compared to those without a psychiatric admission. We used multiple reaction monitoring mass spectrometry to quantify 77 proteins (147 peptides) in serum samples from 60 first-onset drug-naive schizophrenia patients and 77 controls, and 96 proteins (152 peptides) in 892 newborn blood-spot (NBS) samples collected between 1975 and 1985. Both serum and NBS studies showed significant alterations in protein levels. Serum results revealed that Haptoglobin and Plasma protease C1 inhibitor were significantly upregulated in first-onset schizophrenia patients (correctedP < 0.05). Alpha-2-antiplasmin, Complement C4-A and Antithrombin-III were increased in first-onset schizophrenia patients (uncorrectedP-values 0.041, 0.036 and 0.013, respectively) and also increased in newborn babies who later develop schizophrenia (P-values 0.0058, 0.013 and 0.044, respectively). We also tested whether protein abundance at birth was associated with exposure to an urban environment during pregnancy and found highly significant proteomic differences at birth between urban and rural environments. The prediction model for urbanicity had excellent predictive performance in both discovery (area under the receiver operating characteristic curve (AUC) = 0.90) and validation (AUC = 0.89) sample sets. We hope that future biomarker studies based on stored NBS samples will identify prognostic disease indicators and targets for preventive measures for neurodevelopmental conditions, particularly those with onset during early childhood, such as autism spectrum disorder.
Schizophrenia and depression, two poles of endocannabinoid system deregulation
Authors: Rodríguez-Muñoz María , Sánchez-Blázquez Pilar , Callado Luis F. , Meana J. Javier , Garzón-Niño Javier 
Published: December 2017

AbstractThe activity of certain G protein-coupled receptors (GPCRs) and of glutamate N-Methyl-D-aspartate receptors (NMDARs) is altered in both schizophrenia and depression. Using postmortem prefrontal cortex samples from subjects with schizophrenia or depression, we observed a series of opposite changes in the expression of signaling proteins that have been implicated in the cross-talk between GPCRs and NMDARs. Thus, the levels of HINT1 proteins and NMDAR NR1 subunits carrying the C1 cytosolic segment were increased in depressives and decreased in schizophrenics, respect to matched controls. The differences in NR1 C1 subunits were compensated for via altered expression of NR1 subunits lacking the C1 segment; thus, the total number of NR1 subunits was comparable among the three groups. GPCRs influence the function of NR1 C1-containing NMDARs via PKC/Src, and thus, the association of mu-opioid and dopamine 2 receptors with NR1 C1 subunits was augmented in depressives and decreased in schizophrenics. However, the association of cannabinoid 1 receptors (CB1Rs) with NR1 C1 remained nearly constant. Endocannabinoids, via CB1Rs, control the presence of NR1 C1 subunits in the neural membrane. Thus, an altered endocannabinoid system may contribute to the pathophysiology of schizophrenia and depression by modifying the HINT1-NR1 C1/GPCR ratio, thereby altering GPCR-NMDAR cross-regulation.
Catalytic asymmetric synthesis of a nitrogen heterocycle through stereocontrolled direct photoreaction from electronically excited state
Authors: Huang Xiaoqiang , Li Xinyao , Xie Xiulan , Harms Klaus , Riedel Radostan , Meggers Eric 
Published: December 2017

AbstractThe reactivity of photoexcited molecules has been extensively studied for decades but until today direct bond-forming reactions of such excited states in a catalytic and asymmetric fashion are restricted to the synthesis of cyclobutanes via [2 + 2] photocycloadditions. Herein, we demonstrate a previously elusive visible-light-induced catalytic asymmetric [2 + 3] photocycloaddition of alkenes with vinyl azides. A wide range of complex 1-pyrrolines are obtained as single diastereoisomers and with up to >99% enantiomeric excess using a simple reaction setup and mild reaction conditions. The reaction is proposed to proceed through the photoexcitation of a complex out of chiral rhodium catalyst coordinated to α,β-unsaturated N-acylpyrazole substrates. All reactive intermediates remain bound to the catalysts thereby providing a robust catalytic scheme (no exclusion of air necessary) with excellent stereocontrol. This work expands the scope of stereocontrolled bond-forming reactions of photoexcited intermediates by providing catalytic asymmetric access to a key nitrogen heterocycle in organic chemistry.
Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway
Authors: Chao Hsu-Wen , Doi Masao , Fustin Jean-Michel , Chen Huatao , Murase Kimihiko , Maeda Yuki , Hayashi Hida , Tanaka Rina , Sugawa Maho , Mizukuchi Naoki , Yamaguchi Yoshiaki , Yasunaga Jun-ichirou , Matsuoka Masao , Sakai Mashito , Matsumoto Michihiro , Hamada Shinshichi , Okamura Hitoshi 
Published: December 2017

AbstractLiver metabolism undergoes robust circadian oscillations in gene expression and enzymatic activity essential for liver homeostasis, but whether the circadian clock controls homeostatic self-renewal of hepatocytes is unknown. Here we show that hepatocyte polyploidization is markedly accelerated around the central vein, the site of permanent cell self-renewal, in mice deficient in circadian Period genes. In these mice, a massive accumulation of hyperpolyploid mononuclear and binuclear hepatocytes occurs due to impaired mitogen-activated protein kinase phosphatase 1 (Mkp1)-mediated circadian modulation of the extracellular signal-regulated kinase (Erk1/2) activity. Time-lapse imaging of hepatocytes suggests that the reduced activity of Erk1/2 in the midbody during cytokinesis results in abscission failure, leading to polyploidization. Manipulation of Mkp1 phosphatase activity is sufficient to change the ploidy level of hepatocytes. These data provide clear evidence that the Period genes not only orchestrate dynamic changes in metabolic activity, but also regulate homeostatic self-renewal of hepatocytes through Mkp1-Erk1/2 signaling pathway.
A conserved ankyrin repeat-containing protein regulates conoid stability, motility and cell invasion in Toxoplasma gondii
Authors: Long Shaojun , Anthony Bryan , Drewry Lisa L. , Sibley L. David 
Published: December 2017

AbstractApicomplexan parasites are typified by an apical complex that contains a unique microtubule-organizing center (MTOC) that organizes the cytoskeleton. In apicomplexan parasites such as Toxoplasma gondii, the apical complex includes a spiral cap of tubulin-rich fibers called the conoid. Although described ultrastructurally, the composition and functions of the conoid are largely unknown. Here, we localize 11 previously undescribed apical proteins in T. gondii and identify an essential component named conoid protein hub 1 (CPH1), which is conserved in apicomplexan parasites. CPH1 contains ankyrin repeats that are required for structural integrity of the conoid, parasite motility, and host cell invasion. Proximity labeling and protein interaction network analysis reveal that CPH1 functions as a hub linking key motor and structural proteins that contain intrinsically disordered regions and coiled coil domains. Our findings highlight the importance of essential protein hubs in controlling biological networks of MTOCs in early-branching protozoan parasites.
Leukocyte-Associated Immunoglobulin-like Receptor-1 is regulated in human myocardial infarction but its absence does not affect infarct size in mice
Authors: Ellenbroek Guilielmus H. J. M. , de Haan Judith J. , van Klarenbosch Bas R. , Brans Maike A. D. , van de Weg Sander M. , Smeets Mirjam B. , de Jong Sanne , Arslan Fatih , Timmers Leo , Goumans Marie-José T. H. , Hoefer Imo E. , Doevendans Pieter A. , Pasterkamp Gerard , Meyaard Linde , de Jager Saskia C. A. 
Published: December 2017

AbstractHeart failure after myocardial infarction (MI) depends on infarct size and adverse left ventricular (LV) remodelling, both influenced by the inflammatory response. Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor of ITAM-dependent cell activation, present on almost all immune cells. We investigated regulation of LAIR-1 leukocyte expression after MI in patients and hypothesized that its absence in a mouse model of MI would increase infarct size and adverse remodelling. In patients, LAIR-1 expression was increased 3 days compared to 6 weeks after MI on circulating monocytes (24.8 ± 5.3 vs. 21.2 ± 5.1 MFI, p = 0.008) and neutrophils (12.9 ± 4.7 vs. 10.6 ± 3.1 MFI, p = 0.046). In WT and LAIR-1−/− mice, infarct size after ischemia-reperfusion injury was comparable (37.0 ± 14.5 in WT vs. 39.4 ± 12.2% of the area at risk in LAIR-1−/−, p = 0.63). Remodelling after permanent left coronary artery ligation did not differ between WT and LAIR-1−/− mice (end-diastolic volume 133.3 ± 19.3 vs. 132.1 ± 27.9 μL, p = 0.91 and end-systolic volume 112.1 ± 22.2 vs. 106.9 ± 33.5 μL, p = 0.68). Similarly, no differences were observed in inflammatory cell influx or fibrosis. In conclusion, LAIR-1 expression on monocytes and neutrophils is increased in the acute phase after MI in patients, but the absence of LAIR-1 in mice does not influence infarct size, inflammation, fibrosis or adverse cardiac remodelling.
An updated reconstruction of basaltic crust emplacement in Tyrrhenian sea, Italy
Authors: Savelli Carlo , Ligi Marco 
Published: December 2017

AbstractBasaltic crust is present in the oceans and marginal seas. Oceanic accretion from inception to ending may be usefully recognized in small basin setting like the Tyrrhenian. Alternating episodes of strong and moderate extensional tectonics characterized the small Tyrrhenian opening. Hyperextension (drifting) of late-Miocene and latemost Pliocene age was followed by Pliocene and Late Quaternary moderate extension (rifting). Early hyperextension (~7.5–6.3 Ma) acted in the submerged margin of Hercynian Sardinia. Sardinia offshore, E-directed low-angle faults were accompanied by MORB-like volcanism of non linear shape in the shallow Vavilov plain - inherited segment of alpine-age orogen. Late hyperextension (~1.9–1.7 Ma) acted along the central N-S lineament of Vavilov plain, former metamorphic core complex. At the lineament northern side, E-dipping detachment faulting exposed serpentinized peridotite. At the other side, Vavilov volcano was faulted and its east flank tilted westwards. At the same time, volcanism with affinity to transitional MORB induced opening of Marsili basin. The drift episodes were characterized by absence or scarcity of volcanic activity on the conjugated emerged margins. The rift episodes (respectively ~5–1.9 Ma, and ~1/0.8 Ma-Recent) saw growth of major north-south trending volcanoes in bathyal area as intense volcanic activity developed on the continental margins.
Functional characterization and discovery of modulators of SbMATE, the agronomically important aluminium tolerance transporter from Sorghum bicolor
Authors: Doshi Rupak , McGrath Aaron P. , Piñeros Miguel , Szewczyk Paul , Garza Denisse M. , Kochian Leon V. , Chang Geoffrey 
Published: December 2017

AbstractAbout 50% of the world’s arable land is strongly acidic (pH ≤ 5). The low pH solubilizes root-toxic ionic aluminium (Al3+) species from clay minerals, driving the evolution of counteractive adaptations in cultivated crops. The food crop Sorghum bicolor upregulates the membrane-embedded transporter protein SbMATE in its roots. SbMATE mediates efflux of the anionic form of the organic acid, citrate, into the soil rhizosphere, chelating Al3+ ions and thereby imparting Al-resistance based on excluding Al+3 from the growing root tip. Here, we use electrophysiological, radiolabeled, and fluorescence-based transport assays in two heterologous expression systems to establish a broad substrate recognition profile of SbMATE, showing the proton and/or sodium-driven transport of 14C-citrate anion, as well as the organic monovalent cation, ethidium, but not its divalent analog, propidium. We further complement our transport assays by measuring substrate binding to detergent-purified SbMATE protein. Finally, we use the purified membrane protein as an antigen to discover native conformation-binding and transport function-altering nanobodies using an animal-free, mRNA/cDNA display technology. Our results demonstrate the utility of using Pichia pastoris as an efficient eukaryotic host to express large quantities of functional plant transporter proteins. The nanobody discovery approach is applicable to other non-immunogenic plant proteins.
High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling
Authors: Globus Oriane , Evron Tamar , Caspi Michal , Siman-Tov Ronen , Rosin-Arbesfeld Rina 
Published: December 2017

AbstractDifferent cancer types as well as many other diseases are caused by aberrant activation of the canonical Wnt signal transduction pathway, and it is especially implicated in the development and progression of colorectal cancer (CRC). The main effector protein of the canonical Wnt signaling cascade is β-catenin, which binds to the T- cell factor/lymphoid enhancer factor (TCF/LEF) and triggers the activation of Wnt target genes. Here, we identify the serine protease High-Temperature Requirement A1 (HTRA1) as a novel component of the canonical Wnt pathway. We show that the HTRA1 protein inhibits the Wnt/β-catenin signaling, in both paracrine and autocrine manners, and affects the expression of several Wnt target genes. Moreover, HTRA1 forms a complex with β-catenin and reduces the proliferation rates of cells. Taken together, our findings indicate that HTRA1 functions as a novel suppressor of the canonical Wnt signaling pathway.
Identification and expression of CAMTA genes in Populus trichocarpa under biotic and abiotic stress
Authors: Wei Ming , Xu Xuemei , Li Chenghao 
Published: December 2017

AbstractThe calmodulin-binding transcription activators (CAMTAs) transcription factor family plays an important role in normal plant growth and development, as well as in biotic and abiotic stress resistance. In this study, we identified seven CAMTA genes across the whole genome of Populus trichocarpa and analyzed the expression patterns of PtCAMTAs in the root and leaf tissues. Promoter cis-element analysis indicated that most CAMTA genes contained stress- or phytohormone-related cis-elements. Quantitative real-time reverse transcription-PCR (qRT-PCR) indicated indicated that PtCAMTAs were induced by mannitol, NaCl, cold stress, pathogenic infection with A. alternata, and phytohormone treatments with abscisic acid, salicylic acid, and methyl jasmonate. We analyzed the expression of homologous genes between P. trichocarpa and P. ussuriensis and alternative splicing forms of PtCAMTA genes under cold stress. We also performed a network interaction analysis for PtCAMTA proteins to predict their interactions and associations. The results of the present study serve as a basis for future functional studies on the Populus CAMTA family.
Thermoluminescence of coral skeletons: a high-sensitivity proxy of diagenetic alteration of aragonite
Authors: Takada Noriyuki , Suzuki Atsushi , Ishii Hiroshi , Hironaka Katsuyuki , Hironiwa Takayuki 
Published: December 2017

AbstractDiagenetic alteration of aragonite coral skeletons causes changes in their chemical and isotopic compositions. Such altered coral samples are unsuitable for age dating or paleoclimate reconstructions. Recently developed microanalysis techniques have elucidated secondary aragonite precipitation and calcite overgrowth on primary aragonitic coral skeletons, but an effective screening method for bulk samples is still desirable. Although powder X-ray diffraction (XRD) analysis is widely used for this purpose, its detection limit for calcite (1–2% at best) is not sufficient to detect very small amounts of diagenetic calcite. Here, we propose that thermoluminescence (TL) spectra can be used to detect the presence of tiny amounts of secondary calcite in coral skeletons. We used a TL spectrometer with a Fourier-transform detector to detect the calcite component in TL spectra of powdered skeletons of modern and fossil corals (from 127 ka and 3.5 Ma) in which calcite was not detectable by XRD. The key element is manganese, because the TL emission efficiency and the partition coefficient of Mn are greater for calcite than for aragonite. As a result, the calcite spectral component becomes evident. Thus, the TL spectroscopic technique is a highly sensitive tool for screening fossil corals for diagenetic alteration.
New Types of Experiments Reveal that a Neuron Functions as Multiple Independent Threshold Units
Authors: Sardi Shira , Vardi Roni , Sheinin Anton , Goldental Amir , Kanter Ido 
Published: December 2017

AbstractNeurons are the computational elements that compose the brain and their fundamental principles of activity are known for decades. According to the long-lasting computational scheme, each neuron sums the incoming electrical signals via its dendrites and when the membrane potential reaches a certain threshold the neuron typically generates a spike to its axon. Here we present three types of experiments, using neuronal cultures, indicating that each neuron functions as a collection of independent threshold units. The neuron is anisotropically activated following the origin of the arriving signals to the membrane, via its dendritic trees. The first type of experiments demonstrates that a single neuron’s spike waveform typically varies as a function of the stimulation location. The second type reveals that spatial summation is absent for extracellular stimulations from different directions. The third type indicates that spatial summation and subtraction are not achieved when combining intra- and extra- cellular stimulations, as well as for nonlocal time interference, where the precise timings of the stimulations are irrelevant. Results call to re-examine neuronal functionalities beyond the traditional framework, and the advanced computational capabilities and dynamical properties of such complex systems.