bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syngeneic Mesenchymal Stem Cells Reduce Immune Rejection After Induced Pluripotent Stem Cell-Derived Allogeneic Cardiomyocyte Transplantation
Authors: Yoshida Shohei , Miyagawa Shigeru , Toyofuku Toshihiko , Fukushima Satsuki , Kawamura Takuji , Kawamura Ai , Kashiyama Noriyuki , Nakamura Yuki , Toda Koichi , Sawa Yoshiki 
Published: March 2020

AbstractAvoiding immune rejection after allogeneic induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) transplantation is a concern. However, mesenchymal stem cells (MSCs) can suppress immune rejection. To determine whether MSC co-transplantation can reduce immune rejection after allogeneic iPSC-CM transplantation, the latter cell type, harbouring a luciferase transgene, was subcutaneously transplanted alone or together with syngeneic MSCs into BALB/c mice. Bioluminescence imaging revealed that MSC co-transplantation significantly improved graft survival (day 7: iPSC-CMs alone 34 ± 5%; iPSC-CMs with MSCs, 61 ± 7%; P = 0.008). MSC co-transplantation increased CD4 + CD25 + FOXP3 + regulatory T cell numbers, apoptotic CD8-positive T cells, and IL-10 and TGF-beta expression at the implantation site. Analysis using a regulatory T cell depletion model indicated that enhanced regulatory T cell populations in the iPSC-CM with MSC group partially contributed to the extended iPSC-CM survival. Further, MSCs affected activated lymphocytes directly through cell–cell contact, which reduced the CD8/CD4 ratio, the proportion of Th1-positive cells among CD4-positive cells, and the secretion of several inflammation-related cytokines. Syngeneic MSC co-transplantation might thus control allogeneic iPSC-CM rejection by mediating immune tolerance via regulatory T cells and cell–cell contact with activated lymphocytes; this approach has promise for cardiomyogenesis-based therapy using allogeneic iPSC-CMs for severe heart failure.
Metabolomic-guided discovery of cyclic nonribosomal peptides from Xylaria ellisii sp. nov., a leaf and stem endophyte of Vaccinium angustifolium
Authors: Ibrahim Ashraf , Tanney Joey B. , Fei Fan , Seifert Keith A. , Cutler G. Christopher , Capretta Alfredo , Miller J. David , Sumarah Mark W. 
Published: March 2020

AbstractFungal endophytes are sources of novel bioactive compounds but relatively few agriculturally important fruiting plants harboring endophytes have been carefully studied. Previously, we identified a griseofulvin-producing Xylaria species isolated from Vaccinium angustifolium, V. corymbosum, and Pinus strobus. Morphological and genomic analysis determined that it was a new species, described here as Xylaria ellisii. Untargeted high-resolution LC-MS metabolomic analysis of the extracted filtrates and mycelium from 15 blueberry isolates of this endophyte revealed differences in their metabolite profiles. Toxicity screening of the extracts showed that bioactivity was not linked to production of griseofulvin, indicating this species was making additional bioactive compounds. Multivariate statistical analysis of LC-MS data was used to identify key outlier features in the spectra. This allowed potentially new compounds to be targeted for isolation and characterization. This approach resulted in the discovery of eight new proline-containing cyclic nonribosomal peptides, which we have given the trivial names ellisiiamides A-H. Three of these peptides were purified and their structures elucidated by one and two-dimensional nuclear magnetic resonance spectroscopy (1D and 2D NMR) and high-resolution tandem mass spectrometry (HRMS/MS) analysis. The remaining five new compounds were identified and annotated by high-resolution mass spectrometry. Ellisiiamide A demonstrated Gram-negative activity against Escherichia coli BW25113, which is the first reported for this scaffold. Additionally, several known natural products including griseofulvin, dechlorogriseofulvin, epoxy/cytochalasin D, zygosporin E, hirsutatin A, cyclic pentapeptides #1–2 and xylariotide A were also characterized from this species.
Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition
Authors: Magno Luiz Alexandre Viana , Tenza-Ferrer Helia , Collodetti Mélcar , Nicolau Eduardo de Souza , Khlghatyan Jivan , Del’Guidice Thomas , Romano-Silva Marco Aurélio , Beaulieu Jean Martin 
Published: March 2020

AbstractPeripheral biomarker and post-mortem brains studies have shown alterations of neuronal calcium sensor 1 (Ncs-1) expression in people with bipolar disorder or schizophrenia. However, its engagement by psychiatric medications and potential contribution to behavioral regulation remains elusive. We investigated the effect on Ncs-1 expression of valproic acid (VPA), a mood stabilizer used for the management of bipolar disorder. Treatment with VPA induced Ncs-1 gene expression in cell line while chronic administration of this drug to mice increased both Ncs-1 protein and mRNA levels in the mouse frontal cortex. Inhibition of histone deacetylases (HDACs), a known biochemical effect of VPA, did not alter the expression of Ncs-1. In contrast, pharmacological inhibition or genetic downregulation of glycogen synthase kinase 3β (Gsk3β) increased Ncs-1 expression, whereas overexpression of a constitutively active Gsk3β had the opposite effect. Moreover, adeno-associated virus-mediated Ncs-1 overexpression in mouse frontal cortex caused responses similar to those elicited by VPA or lithium in tests evaluating social and mood-related behaviors. These findings indicate that VPA increases frontal cortex Ncs-1 gene expression as a result of Gsk3 inhibition. Furthermore, behavioral changes induced by Ncs-1 overexpression support a contribution of this mechanism in the regulation of behavior by VPA and potentially other psychoactive medications inhibiting Gsk3 activity.
Duan-Nai-An, A Yeast Probiotic, Improves Intestinal Mucosa Integrity and Immune Function in Weaned Piglets
Authors: Zhaxi Yingpai , Meng Xiaoqin , Wang Wenhui , Wang Ling , He Zhuolin , Zhang Xuejing , Pu Wanxia 
Published: March 2020

AbstractPost-weaning diarrhea commonly occurs in piglets and results in significant economic loss to swine producers. Non-antibiotic measures for managing post-weaning diarrhea are critically needed. Duan-Nai-An, a probiotic produced from the yeast fermentation of egg whites, was previously shown to optimize intestinal flora and reduce the incidence of clinical diarrhea in weaning piglets. To study the effects of Duan-Nai-An on mucosal integrity and immunity in pig intestine, we examined the microstructure and ultrastructure of the intestines of weaned pigs with or without Duan-Nai-An as a feed supplement. The piglets of the Duan-Nai-An-fed group developed intestines with intact columnar epithelia covered by tightly packed microvilli on the apical surface. However, piglets of the control group (no supplement) showed villous atrophy and thinning, microvillus slough, and in the severe cases, damage of intestinal epithelia and exposure of the underlying lamina propria. Moreover, piglets of the Duan-Nai-An-fed group showed apparent plasmocyte hyperplasia, increased lymphoid nodule numbers, well-developed Peyer’s Patchs, and apparent germinal centers. The lymphoid tissues of the control group were far less developed, showing lymph node atrophy, lymphocyte reduction, degeneration, and necrosis. These results indicate that Duan-Nai-An improves the development of the intestinal structures and lymphoid tissues and promotes intestinal health in weaned piglets.
Megakaryocytes contain extranuclear histones and may be a source of platelet-associated histones during sepsis
Authors: Frydman Galit H. , Tessier Shannon N. , Wong Keith H. K. , Vanderburg Charles R. , Fox James G. , Toner Mehmet , Tompkins Ronald G. , Irimia Daniel 
Published: March 2020

AbstractHistones are typically located within the intracellular compartment, and more specifically, within the nucleus. When histones are located within the extracellular compartment, they change roles and become damage-associated molecular patterns (DAMPs), promoting inflammation and coagulation. Patients with sepsis have increased levels of extracellular histones, which have been shown to correlate with poor prognosis and the development of sepsis-related sequelae, such as end-organ damage. Until now, neutrophils were assumed to be the primary source of circulating histones during sepsis. In this paper, we show that megakaryocytes contain extranuclear histones and transfer histones to their platelet progeny. Upon examination of isolated platelets from patients with sepsis, we identified that patients with sepsis have increased amounts of platelet-associated histones (PAHs), which appear to be correlated with the type of infection. Taken together, these results suggest that megakaryocytes and platelets may be a source of circulating histones during sepsis and should be further explored.
Nomogram for Prediction of Bronchial Mucus Plugs in Children with Mycoplasma pneumoniae Pneumonia
Authors: Xu Xuefeng , Li Huiwen , Sheng Yuanjian , Wu Lei , Wang Danli , Liu Lingyue , Tong Yu , Chen Zhimin 
Published: March 2020

AbstractThe presence of bronchial mucus plugs (BMP) in children with Mycoplasma pneumoniae pneumonia (MPP) results in delayed clinical and radiographic resolution and long-standing pulmonary sequelae. The predictive factors associated with BMP formation remains poorly defined. Nomograms to predict BMP presence in children with MPP were proposed using a cohort of patients who underwent bronchoscopy intervention at Children’s Hospital in Eastern China. Patients with MPP in an earlier period formed the training cohort (n = 872) for nomogram development, and those thereafter formed the validation cohort (n = 399) to confirmed model’s performance. BMP in children with MPP were found in 196 (22.5%) and 91(22.8%) patients in the training and validation cohorts, respectively. The independent risk factors associated with BMP were age >5years (OR 2.06; 95% CI 1.43 to 2.98), higher IL-10 level (>10 ng/L, 2.19; 95% CI 1.46 to 3.28), higher IFN-γ level (>30 ng/L, 1.69; 95% CI 1.13 to 2.54), and presence of complication (3.43; 95% CI 1.45 to 8.09). Incorporating these 4 factors, the nomogram achieved good concordance indexes of 0.771(95% CI, 0.734–0.808) and 0.796 (95% CI, 0.744–0.848) in predicting BMP in the training and validation cohorts, respectively. The nomogram achieved an optimal prediction of BMP in children with MPP. Using this model, the risk of BMP formation would be determined, contributing to a rational therapeutic choice.
Electrophysiologically and behaviourally active semiochemicals identified from bed bug refuge substrate
Authors: Weeks E. N. I. , Logan J. G. , Birkett M. A. , Caulfield J. C. , Gezan S. A. , Welham S. J. , Brugman V. A. , Pickett J. A. , Cameron M. M. 
Published: March 2020

AbstractBed bugs are pests of public health importance due to their relentless biting habits that can lead to allergies, secondary infections and mental health issues. When not feeding on human blood bed bugs aggregate in refuges close to human hosts. This aggregation behaviour could be exploited to lure bed bugs into traps for surveillance, treatment efficacy monitoring and mass trapping efforts, if the responsible cues are identified. The aim of this study was to identify and quantify the bed bug aggregation pheromone. Volatile chemicals were collected from bed bug-exposed papers, which are known to induce aggregation behaviour, by air entrainment. This extract was tested for behavioural and electrophysiological activity using a still-air olfactometer and electroantennography, respectively. Coupled gas chromatography-electroantennography (GC-EAG) was used to screen the extract and the GC-EAG-active chemicals, benzaldehyde, hexanal, (E)-2-octenal, octanal, nonanal, decanal, heptanal, (R,S)-1-octen-3-ol, 3-carene, β-phellandrene, (3E,5E)-octadien-2-one, (E)-2-nonenal, 2-decanone, dodecane, nonanoic acid, 2-(2-butoxyethoxy)ethyl acetate, (E)-2-undecanal and (S)-germacrene D, were identified by GC-mass spectrometry and quantified by GC. Synthetic blends, comprising 6, 16, and 18 compounds, at natural ratios, were then tested in the still-air olfactometer to determine behavioural activity. These aggregation chemicals can be manufactured into a lure that could be used to improve bed bug management.
Janzen-Connell effects shape gene flow patterns and realized fitness in the tropical dioecious tree Spondias purpurea (ANACARDIACEAE)
Authors: Cristóbal-Pérez E. Jacob , Fuchs Eric J. , Olivares-Pinto Ulises , Quesada Mauricio 
Published: March 2020

AbstractPollination and seed dispersal patterns determine gene flow within plant populations. In tropical forests, a high proportion of trees are dioecious, insect pollinated and dispersed by vertebrates. Dispersal vectors and density dependent factors may modulate realized gene flow and influence the magnitude of Fine Scale Genetic Structure (FSGS), affecting individual fitness.Spondias purpureais a vertebrate-dispersed, insect-pollinated dioecious tropical tree. We assessed the influence of sex ratio, effective and realized gene flow on genetic diversity, FSGS and individual fitness within a 30 ha plot in the tropical dry forest reserve of Chamela-Cuixmala, Mexico. All individuals within the plot were tagged, geo-referenced and sampled for genetic analysis. We measured dbh and monitored sex expression during two reproductive seasons for all individuals. We collected seeds directly from maternal trees for effective pollen dispersal analysis, and analyzed established seedlings to assess realized pollen and seed dispersal. Nine microsatellite loci were used to describe genetic diversity parameters, FSGS and gene flow patterns among different size classes. A total of 354 individuals were located and classified into three size classes based on their dbh (<10, 10–20, and >20 cm). Population sex ratios were male biased and diametric size distributions differed among sexes, these differences may be the result of precocious male reproduction at early stages. Autocorrelation analyses indicate low FSGS (Fj <0.07) across all size classes. Long realized pollen and seed dispersal and differences among effective and realized gene flow were detected. In our study site low FSGS is associated with high gene flow levels. Effective and realized gene flow indicate a population recruitment curve indicating Janzen-Connell effects and suggesting fitness advantages for long-distance pollen and seed dispersal events.
Heme b distributions through the Atlantic Ocean: evidence for “anemic” phytoplankton populations
Authors: Louropoulou Evangelia , Gledhill Martha , Achterberg Eric P. , Browning Thomas J. , Honey David J. , Schmitz Ruth A. , Tagliabue Alessandro 
Published: March 2020

AbstractHeme b is an iron-containing cofactor in hemoproteins that participates in the fundamental processes of photosynthesis and respiration in phytoplankton. Heme b concentrations typically decline in waters with low iron concentrations but due to lack of field data, the distribution of heme b in particulate material in the ocean is poorly constrained. Here we report particulate heme b distributions across the Atlantic Ocean (59.9°N to 34.6°S). Heme b concentrations in surface waters ranged from 0.10 to 33.7 pmol L−1 (median = 1.47 pmol L−1, n = 974) and were highest in regions with a high biomass. The ratio of heme b to particulate organic carbon (POC) exhibited a mean value of 0.44 μmol heme b mol−1 POC. We identified the ratio of 0.10 µmol heme b mol−1 POC as the cut-off between heme b replete and heme b deficient (anemic) phytoplankton. By this definition, we observed anemic phytoplankton populations in the Subtropical South Atlantic and Irminger Basin. Comparison of observed and modelled heme b suggested that heme b could account for between 0.17–9.1% of biogenic iron. Our large scale observations of heme b relative to organic matter provide further evidence of the impact of changes in iron supply on phytoplankton iron status across the Atlantic Ocean.
Effect of AlOx protection layer on AgNWs for flexible transparent heater
Authors: Lee Joon-Min , Kim Young-Hoi , Kim Han-Ki , Kim Hye-Jin , Hong Chan-Hwa 
Published: March 2020

AbstractWe indicated high performance and stability transparent heaters based on AlOx covered Ag nanowires. We obtained an AlOx covered Ag nanowire thin film which has a 47 ohm/sq of sheet resistance and 88.1% (substrate included) of transmittance at 600 nm on a flexible substrate. We demonstrate that the thin AlOx layer leads to increased contact area at the junction of Ag nanowires, which contributes to lower sheet resistance and improved adhesion of Ag nanowires. Furthermore, high stability and flexibility of Ag nanowire have been achieved by the AlOx layer. Finally, we fabricated a flexible transparent heater with AlOx covered Ag nanowire, and obtained a temperature of 81 °C within 40 sec at the driven voltage of 7 V with fast response and uniform temperature distribution. Therefore, the AlOx covered Ag nanowire film is a promising candidate for the application of the flexible transparent heaters.
Polyethylenimine based magnetic nanoparticles mediated non-viral CRISPR/Cas9 system for genome editing
Authors: Rohiwal S. S. , Dvorakova N. , Klima J. , Vaskovicova M. , Senigl F. , Slouf M. , Pavlova E. , Stepanek P. , Babuka D. , Benes H. , Ellederova Z. , Stieger K. 
Published: March 2020

AbstractClustered regularly interspaced short palindromic repeats-associated protein (CRISPR/Cas9) system has become a revolutionary tool for gene editing. Since viral delivery systems have significant side effects, and naked DNA delivery is not an option, the nontoxic, non-viral delivery of CRISPR/Cas9 components would significantly improve future therapeutic delivery. In this study, we aim at characterizing nanoparticles to deliver plasmid DNA encoding for the CRISPR-Cas system in eukaryotic cells in vitro. CRISPR/Cas9 complexed polyethylenimine (PEI) magnetic nanoparticles (MNPs) were generated. We used a stable HEK293 cell line expressing the traffic light reporter (TLR-3) system to evaluate efficient homology- directed repair (HDR) and non-homologous end joining (NHEJ) events following transfection with NPs. MNPs have been synthesized by co-precipitation with the average particle size around 20 nm in diameter. The dynamic light scattering and zeta potential measurements showed that NPs exhibited narrow size distribution and sufficient colloidal stability. Genome editing events were as efficient as compared to standard lipofectamine transfection. Our approach tested non-viral delivery of CRISPR/Cas9 and DNA template to perform HDR and NHEJ in the same assay. We demonstrated that PEI-MNPs is a promising delivery system for plasmids encoding CRISPR/Cas9 and template DNA and thus can improve safety and utility of gene editing.
Accelerated onset of CNS prion disease in mice co-infected with a gastrointestinal helminth pathogen during the preclinical phase
Authors: Donaldson David S. , Bradford Barry M. , Else Kathryn J. , Mabbott Neil A. 
Published: March 2020

AbstractPrion infections in the central nervous system (CNS) can cause extensive neurodegeneration. Systemic inflammation can affect the progression of some neurodegenerative disorders. Therefore, we used the gastrointestinal helminth pathogen Trichuris muris to test the hypothesis that a chronic systemic inflammatory response to a gastrointestinal infection would similarly affect CNS prion disease pathogenesis. Mice were injected with prions directly into the CNS and subsequently orally co-infected with T. muris before the onset of clinical signs. We show that co-infection with a low dose of T. muris that leads to the development of a chronic T helper cell type 1-polarized systemic immune response accelerated the onset of clinical prion disease. In contrast, co-infection with a high dose of T. muris that induces a T helper cell type 2-polarized immune response did not affect prion disease pathogenesis. The reduced survival times in mice co-infected with a low dose of T. muris on d 105 after CNS prion infection coincided with enhanced astrocyte activation in the brain during the preclinical phase. These data aid our understanding of how systemic inflammation may augment the progression of neurodegeneration in the CNS.
Electrophysiological responses to images ranging in motivational salience: Attentional abnormalities associated with schizophrenia-spectrum disorder risk
Authors: Martin Elizabeth A. , Li Lilian Yanqing , Castro Mayan K. 
Published: March 2020

AbstractIndividuals at risk for schizophrenia-spectrum disorders display abnormalities related to motivational salience, or the ability of stimuli to elicit attention due to associations with rewards or punishments. However, the nature of these abnormalities is unclear because most focus on responses to stimuli from broad “pleasant” and “unpleasant” categories and ignore the variation of motivational salience within these categories. In two groups at risk for schizophrenia-spectrum disorders—a Social Anhedonia group and a Psychotic-like Experiences group—and a control group, the current study examined event-related potential components sensitive to motivational salience—the Early Posterior Negativity (EPN), reflecting earlier selective attention, and the Late Positive Potential (LPP), reflecting sustained attention. Compared to controls, the Social Anhedonia group showed smaller increases in the EPN in response to erotica and smaller increases in the LPP as the motivational salience of pleasant images increased (exciting<affiliative<erotica). In contrast, the Psychotic-like Experiences group had larger increases in LPP amplitudes as the motivational salience of pleasant images increased. Also, both at-risk groups showed larger increases in the LPP to threatening images but smaller increases to mutilation images. These findings suggest that examining abnormalities beyond those associated with broad categories may be a way to identify mechanisms of dysfunction.
Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study
Authors: Park Se-Jun , Lee Eunyoung , Lee Kihwang , Park Bumhee , Chung Yoo-Ri 
Published: March 2020

AbstractWe investigated the prevalence of retinal vascular occlusion and intraocular bleeding and compare their risks in patients undergoing anticoagulant therapy, either with non-vitamin K-antagonist oral anticoagulants (NOAC) or warfarin. We performed a cohort study (January 2015 to April 2018) in 281,970 patients with nonvalvular atrial fibrillation (AF) using health claims in the nationwide database of the Health Insurance Review and Assessment service of Korea. A Cox-proportional hazard regression was used to calculate the hazard ratio (HR) for retinal vascular occlusion or intraocular bleeding. The HR of retinal vascular occlusion was estimated to 1.59 (95% confidence interval [CI], 1.35–1.86) for NOAC users compared to that with warfarin users. Among the various types of NOACs, all NOACs showed higher risk of retinal vascular occlusion than did warfarin. For intraocular bleeding, the HR was estimated to be 0.86 (95% CI, 0.75–0.98) for NOAC users compared with that with warfarin users. The risk of retinal vascular occlusion was higher in NOAC users than in warfarin users, while the risk of intraocular bleeding was lower with NOAC therapy. NOACs were not found to be as effective as warfarin for retinal vascular occlusion, but safe in terms of intraocular bleeding.