bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Defensin-5 Blocks Ethanol and Colitis-Induced Dysbiosis, Tight Junction Disruption and Inflammation in Mouse Intestine
Authors: Shukla Pradeep K. , Meena Avtar S. , Rao Vaishnavi , Rao Roshan G. , Balazs Louisa , Rao RadhaKrishna 
Published: October 2018

AbstractAlcohol consumption has been shown to cause dysbiosis, but the mechanism involved in it is unknown. Recurrent colitis is known to induce expression of α-defensins in the colon, but the effect of alcohol consumption on it is not known. We investigated the effect of ethanol on α-defensin expression in the small intestine and colitis-induced expression in colon in mice. Furthermore, we evaluated the effect of human defensin-5 (HD5) on ethanol and colitis-induced gut barrier dysfunction and mucosal damage. Recurrent colitis was induced by feeding dextran sulfate sodium (DSS), 3 cycles of 5-days each with 15 days intervals, followed by 30-days remission. Ethanol was fed during the intervals and recovery in a liquid diet with or without HD5. Expression of α-defensins, tight junction (TJ) integrity and cytokine/chemokine expression were analyzed. Chronic ethanol feeding reduced α-defensin expression in the small intestine and colitis-induced defensin expression in the colon. HD5 attenuated the growth of enterotoxigenic Bacteriodes fragilis and E. coli, but had no effect on non-toxigenic Bacteriodes fragilis or probiotics, the Lactobacilli. Ethanol and colitis elevated Enterobacteriaceae, Firmicutes and Firmicutes to Bacteriodetes ratio in colonic mucosa. HD5 feeding attenuated ethanol and colitis-induced dysbiosis, disruption of intestinal epithelial TJ, mucosal inflammation, expression of pro-inflammatory cytokines and chemokines in the small intestine and colon, and endotoxemia. These results demonstrate that ethanol suppresses intestinal α-defensin expression, leading to dysbiosis, barrier dysfunction, inflammation and endotoxemia. HD5 feeding attenuates intestinal injury caused by ethanol and colitis, indicating that defensin expression is a potential target for treatment of alcoholic tissue injury and colitis.
Omega-3 polyunsaturated fatty acids do not fluidify bilayers in the liquid-crystalline state
Authors: De Santis Augusta , Varela Yaiza , Sot Jesús , D’Errico Gerardino , Goñi Félix M. , Alonso Alicia 
Published: October 2018

AbstractThis work reports on the effects of two omega-3 fatty acids, namely docosahexaenoic (C22:64,7,10,13,16,19) acid (DHA), and eicosapentaenoic (C20:55,8,11,14,17) acid (EPA), with oleic (C18:19) acid (OA) as a control, on the gel-liquid crystalline phase transition of dipalmitoyl phosphatidylcholine (DPPC). Mainly differential scanning calorimetry has been used, together with Laurdan fluorescence, and confocal fluorescence microscopy. All three fatty acids DHA, EPA and OA exhibited fluidifying properties when added to the DPPC bilayers, decreasing the main transition temperature. DHA and EPA were somewhat more effective than OA in this respect, but the effects of all three were of the same order of magnitude, thus the long-chain omega-3 fatty acids failed to exhibit any peculiar fluidifying potency. The same was true when the omega-3 fatty acids were esterified in the sn-2 position of a phosphatidylcholine. Moreover the omega-3 fatty acids had very small or no effects on the fluidity of bilayers in the liquid-crystalline, or fluid disordered state (egg phosphatidylcholine and others), or in the fluid ordered state (phospholipid: cholesterol mixtures). The hypothesis that some physiological effects of long-chain omega-3 fatty acids could be related to their special fluidifying properties is not supported by these data.
Flexural phonons in supported graphene: from pinning to localization
Authors: Zhao Wei L. Z. , Tikhonov Konstantin S. , Finkel’stein Alexander M. 
Published: October 2018

AbstractWe identify graphene layer on a disordered substrate as a system where localization of phonons can be observed. Generally, observation of localization for scattering waves is not simple, because the Rayleigh scattering is inversely proportional to a high power of wavelength. The situation is radically different for the out of plane vibrations, so-called flexural phonons, scattered by pinning centers induced by a substrate. In this case, the scattering time for vanishing wave vector tends to a finite limit. One may, therefore, expect that physics of the flexural phonons exhibits features characteristic for electron localization in two dimensions, albeit without complications caused by the electron-electron interactions. We confirm this idea by calculating statistical properties of the Anderson localization of flexural phonons for a model of elastic sheet in the presence of the pinning centers. Finally, we discuss possible manifestations of the flexural phonons, including the localized ones, in the electronic thermal conductance.
Anatomy of the Campi Flegrei caldera using Enhanced Seismic Tomography Models
Authors: Calò Marco , Tramelli Anna 
Published: October 2018

AbstractCampi Flegrei caldera (Southern Italy) is a densely inhabited area and suffered several unrest episodes in the last centuries. The dynamic of the caldera is highly debated because of conflicting interpretations. Here we present a detailed reconstruction of the Campi Flegrei structure obtained using the microseismicity recorded during the 1984 unrest. Enhanced Seismic Tomography models obtained with these data allow us describing seismic velocities, attenuation, and scattering patterns. Results show: (1) a plumbing system with a diameter of 1 km located between 2.3 km and 4 km depth (2) a 0.5 km thick caprock located at 2 km depth interpreted as the main structure regulating the fluid interchange between deep and shallow sectors of the caldera, (3) the shape and volume of a shallow reservoir beneath the city of Pozzuoli; this reservoir played a key role during the 1982–1984 unrest, (4) several small reservoirs beneath the main craters of the caldera. All these features fit into the debated question on magmatic or hydrothermal mechanism driving the caldera deformation resulting of crucial importance to allow a better assessment of the hazard.
Dopamine release in mushroom bodies of the honey bee (Apis mellifera L.) in response to aversive stimulation
Authors: Jarriault David , Fuller Justine , Hyland Brian I. , Mercer Alison R. 
Published: October 2018

AbstractInDrosophila melanogaster, aversive (electric shock) stimuli have been shown to activate subpopulations of dopaminergic neurons with terminals in the mushroom bodies (MBs) of the brain. While there is compelling evidence that dopamine (DA)-induced synaptic plasticity underpins the formation of aversive memories in insects, the mechanisms involved have yet to be fully resolved. Here we take advantage of the accessibility of MBs in the brain of the honey bee to examine, using fast scan cyclic voltammetry, the kinetics of DA release and reuptakein vivoin response to electric shock, and to investigate factors that modulate the release of this amine. DA increased transiently in the MBs in response to electric shock stimuli. The magnitude of release varied depending on stimulus duration and intensity, and a strong correlation was identified between DA release and the intensity of behavioural responses to shock. With repeated stimulation, peak DA levels increased. However, the amount of DA released on the first stimulation pulse typically exceeded that evoked by subsequent pulses. No signal was detected in response to odour alone. Interestingly, however, if odour presentation was paired with electric shock, DA release was enhanced. These results set the stage for analysing the mechanisms that modulate DA release in the MBs of the bee.
Engineering Lineage Potency and Plasticity of Stem Cells using Epigenetic Molecules
Authors: Dhaliwal Anandika , Pelka Sandra , Gray David S. , Moghe Prabhas V. 
Published: October 2018

AbstractStem cells are considered as a multipotent regenerative source for diseased and dysfunctional tissues. Despite the promise of stem cells, the inherent capacity of stem cells to convert to tissue-specific lineages can present a major challenge to the use of stem cells for regenerative medicine. We hypothesized that epigenetic regulating molecules can modulate the stem cell’s developmental program, and thus potentially overcome the limited lineage differentiation that human stem cells exhibit based on the source and processing of stem cells. In this study, we screened a library of 84 small molecule pharmacological agents indicated in nucleosomal modification and identified a sub-set of specific molecules that influenced osteogenesis in human mesenchymal stem cells (hMSCs) while maintaining cell viability in-vitro. Pre-treatment with five candidate hits, Gemcitabine, Decitabine, I-CBP112, Chidamide, and SIRT1/2 inhibitor IV, maximally enhanced osteogenesis in-vitro. In contrast, five distinct molecules, 4-Iodo-SAHA, Scriptaid, AGK2, CI-amidine and Delphidine Chloride maximally inhibited osteogenesis. We then tested the role of these molecules on hMSCs derived from aged human donors and report that small epigenetic molecules, namely Gemcitabine and Chidamide, can significantly promote osteogenic differentiation by 5.9- and 2.3-fold, respectively. Taken together, this study demonstrates new applications of identified small molecule drugs for sensitively regulating the lineage plasticity fates of bone-marrow derived mesenchymal stem cells through modulating the epigenetic profile of the cells.
An immune cell spray (ICS) formulation allows for the delivery of functional monocyte/macrophages
Authors: Beneke Valerie , Küster Fennja , Neehus Anna-Lena , Hesse Christina , Lopez-Rodriguez Elena , Haake Kathrin , Rafiei Hashtchin Anna , Schott Juliane Wilhelmine , Walter Dorothee , Braun Armin , Wolkers Willem F. , Ackermann Mania , Lachmann Nico 
Published: October 2018

AbstractMacrophages are key cells of the innate immune system and act as tissue resident macrophages (TRMs) in the homeostasis of various tissues. Given their unique functions and therapeutic use as well as the feasibility to derive macrophages in vitro from hematopoietic stem cell (HSC) sources, we propose an “easy-to-use” immune cell spray (ICS) formulation to effectively deliver HSC-derived macrophages. To achieve this aim, we used classical pump spray devices to spray either the human myeloid cell line U937 or primary murine HSC-derived macrophages. For both cell types used, one puff could deliver cells with maintained morphology and functionality. Of note, cells tolerated the spraying process very well with a recovery of more than 90%. In addition, we used osmotic preconditioning to reduce the overall cell size of macrophages. While a 800 mosm hyperosmolar sucrose solution was able to reduce the cell size by 27%, we identified 600 mosm to be effective to reduce the cell size by 15% while maintaining macrophage morphology and functionality. Using an isolated perfused rat lung preparation, the combinatorial use of the ICS with preconditioned and genetically labeled U937 cells allowed the intra-pulmonary delivery of cells, thus paving the way for a new cell delivery platform.
Two fluid model in low energy excited states within spin-ice systems
Authors: López-Bara F. I. , López-Aguilar F. 
Published: October 2018

AbstractExcitations in magnetic structures of the so-called spin-ice materials generate two different peaks in the specific heat and anomalies in entropy in the temperature interval between 0 and 1 K. These points are due to the existence of two low-energy excited global states which seem to transit from a bosonic condensate towards a magnetic neutral plasma in a narrow temperature interval between 0.05 ≤ T ≤ 1 K. In this paper, we determine the characteristic features of two states and we analyze the possibilities of existence of a BEC state and its phase transition to the magnetic plasma state from a model of two magnetic charge fluids. From the structural analysis of the many-body excitation states, we obtain theoretical results about entropy and specific heat since these two key physical magnitudes announce the phase transitions. We give criteria for distinguishing if some of these phase transitions is of either first or second order.
Structure of bacterial oligosaccharyltransferase PglB bound to a reactive LLO and an inhibitory peptide
Authors: Napiórkowska Maja , Boilevin Jérémy , Darbre Tamis , Reymond Jean-Louis , Locher Kaspar P. 
Published: October 2018

AbstractOligosaccharyltransferase (OST) is a key enzyme of the N-glycosylation pathway, where it catalyzes the transfer of a glycan from a lipid-linked oligosaccharide (LLO) to an acceptor asparagine within the conserved sequon N-X-T/S. A previous structure of a ternary complex of bacterial single subunit OST, PglB, bound to a non-hydrolyzable LLO analog and a wild type acceptor peptide showed how both substrates bind and how an external loop (EL5) of the enzyme provided specific substrate-binding contacts. However, there was a relatively large separation of the substrates at the active site. Here we present the X-ray structure of PglB bound to a reactive LLO analog and an inhibitory peptide, revealing previously unobserved interactions in the active site. We found that the atoms forming the N-glycosidic bond (C-1 of the GlcNAc moiety of LLO and the –NH2 group of the peptide) are closer than in the previous structure, suggesting that we have captured a conformation closer to the transition state of the reaction. We find that the distance between the divalent metal ion and the glycosidic oxygen of LLO is now 4 Å, suggesting that the metal stabilizes the leaving group of the nucleophilic substitution reaction. Further, the carboxylate group of a conserved aspartate of PglB mediates an interaction network between the reducing-end sugar of the LLO, the asparagine side chain of the acceptor peptide, and a bound divalent metal ion. The interactions identified in this novel state are likely to be relevant in the catalytic mechanisms of all OSTs.
Single molecule localisation microscopy reveals how HIV-1 Gag proteins sense membrane virus assembly sites in living host CD4 T cells
Authors: Floderer Charlotte , Masson Jean-Baptiste , Boilley Elise , Georgeault Sonia , Merida Peggy , El Beheiry Mohamed , Dahan Maxime , Roingeard Philippe , Sibarita Jean-Baptiste , Favard Cyril , Muriaux Delphine 
Published: October 2018

AbstractMonitoring virus assembly at the nanoscale in host cells remains a major challenge. Human immunodeficiency virus type 1 (HIV-1) components are addressed to the plasma membrane where they assemble to form spherical particles of 100 nm in diameter. Interestingly, HIV-1 Gag protein expression alone is sufficient to produce virus-like particles (VLPs) that resemble the immature virus. Here, we monitored VLP formation at the plasma membrane of host CD4+ T cells using a newly developed workflow allowing the analysis of long duration recordings of single-molecule Gag protein localisation and movement. Comparison of Gag assembling platforms in CD4+ T cells expressing wild type or assembly-defective Gag mutant proteins showed that VLP formation lasts roughly 15 minutes with an assembly time of 5 minutes. Trapping energy maps, built from membrane associated Gag protein movements, showed that one third of the assembling energy is due to direct Gag capsid-capsid interaction while the remaining two thirds require the nucleocapsid-RNA interactions. Finally, we show that the viral RNA genome does not increase the attraction of Gag at the membrane towards the assembling site but rather acts as a spatiotemporal coordinator of the membrane assembly process.
Mining latent information in PTSD psychometrics with fuzziness for effective diagnoses
Authors: Li Yuanyuan , Xiong Xi , Qiu Changjian , Wang Qiang , Xu Jiajun 
Published: October 2018

AbstractThe options of traditional self-report rating-scale, like the PTSD Checklist Civilian (PCL-C) scale, have no clear boundaries which might cause considerable biases and low effectiveness. This research aimed to explore the feasibility of using fuzzy set in the data processing to promote the screening effectiveness of PCL-C in real-life practical settings. The sensitivity, specificity, Youden’s index etc., of PCL-C at different cutoff lines (38, 44 and 50 respectively) were analyzed and compared with those of fuzzy set approach processing. In practice, no matter the cutoff line of the PCL-C was set at 50, 44 or 38, the PCL-C showed good specificity, but failed to exhibit good sensitivity and screening effectiveness. The highest sensitivity was at 65.22%, with Youden’s index being 0.64. After fuzzy processing, the fuzzy-PCL-C’s sensitivity increased to 91.30%, Youden’s index rose to 0.91, having seen marked augmentation. In conclusion, this study indicates that fuzzy set can be used in the data processing of psychiatric scales which have no clear definition standard of the options to improve the effectiveness of the scales.
Brassica yellows virus’ movement protein upregulates anthocyanin accumulation, leading to the development of purple leaf symptoms on Arabidopsis thaliana
Authors: Chen Xiang-Ru , Wang Ying , Zhao Hang-Hai , Zhang Xiao-Yan , Wang Xian-Bing , Li Da-Wei , Yu Jia-Lin , Han Cheng-Gui 
Published: October 2018

AbstractPoleroviruses are widely distributed and often of great economic importance because they cause a variety of symptoms, such as the rolling of young leaves, leaf color changes, and plant decline, in infected plants. However, the molecular mechanism behind these viral-induced symptoms is still unknown. Here, we verified the pathogenicity of the polerovirus Brassica yellows virus (BrYV) by transforming its full-length amplicon intoArabidopsis thaliana, which resulted in many abnormal phenotypes. To better understand the interactions between BrYV and its host, global transcriptome profiles of the transgenic plants were compared with that of non-transgenic Arabidopsis plants. An association between the BrYV- induced purple leaf symptoms and the activation of anthocyanin biosynthesis was noted. Using the transgenic approach, we found that movement protein of BrYV was responsible for the induction of these coloration symptoms. Collectively, our findings demonstrate the BrYV’ pathogenicity and show that the BrYV-induced purple leaf symptom resulted from its movement protein stimulating anthocyanin accumulation.
TRIAMF: A New Method for Delivery of Cas9 Ribonucleoprotein Complex to Human Hematopoietic Stem Cells
Authors: Yen Jonathan , Fiorino Michael , Liu Yi , Paula Steve , Clarkson Scott , Quinn Lisa , Tschantz William R. , Klock Heath , Guo Ning , Russ Carsten , Yu Vionnie W. C. , Mickanin Craig , Stevenson Susan C. , Lee Cameron , Yang Yi 
Published: October 2018

AbstractCRISPR/Cas9 mediated gene editing of patient-derived hematopoietic stem and progenitor cells (HSPCs) ex vivo followed by autologous transplantation of the edited HSPCs back to the patient can provide a potential cure for monogenic blood disorders such as β-hemoglobinopathies. One challenge for this strategy is efficient delivery of the ribonucleoprotein (RNP) complex, consisting of purified Cas9 protein and guide RNA, into HSPCs. Because β-hemoglobinopathies are most prevalent in developing countries, it is desirable to have a reliable, efficient, easy-to-use and cost effective delivery method. With this goal in mind, we developed TRansmembrane Internalization Assisted by Membrane Filtration (TRIAMF), a new method to quickly and effectively deliver RNPs into HSPCs by passing a RNP and cell mixture through a filter membrane. We achieved robust gene editing in HSPCs using TRIAMF and demonstrated that the multilineage colony forming capacities and the competence for engraftment in immunocompromised mice of HSPCs were preserved post TRIAMF treatment. TRIAMF is a custom designed system using inexpensive components and has the capacity to process HSPCs at clinical scale.
Effect of Statins on Renal Function in Chronic Kidney Disease Patients
Authors: Hu Ping-Jen , Wu Mei-Yi , Lin Tsu-Chen , Chen Tzu-Ting , Wu Yun-Chun , Su Sui-Lung , Lu Kuo-Cheng , Chen Jin-Shuen , Sung Fung-Chang , Lee Chien-Te , Yang Yu , Hwang Shang-Jyh , Wang Ming-Cheng , Hsu Yung-Ho , Chiou Hung-Yi , Wong Chung-Shun , Lin Yuh-Feng 
Published: October 2018

AbstractDyslipidemia is associated with glomerular injury. However, the effect of statins on chronic kidney disease (CKD) progression remains controversial. We aimed to investigate the efficacy of statins for renal protection in patients with CKD. The retrospective cohort study comprised 3441 patients diagnosed with CKD in multiple medical centers. We divided the patients into two cohorts based on statin prescription, and compared proportions and risks of CKD progression events between the two groups. CKD progression event was defined as an average annual decline of eGFR >5 mL/min/1.73 m2 or advancement to the dialysis stage. The result revealed that among all incident patients with CKD, 28.7% and 30.3% of the users and nonusers demonstrated CKD progression, respectively. The crude odds ratio (OR) of CKD progression was 0.93 [95% confidence interval (CI) 0.78–1.10]. After adjustment for baseline characteristics, the adjusted OR was 0.80 (95% CI 0.63–1.01). The sensitivity analysis results showed consistent OR for CKD progression, stratification by age, sex, Charlson score, and statins use within 1 year before index date. The effect of statins was significant in patients with CKD stage 3B-5 (OR 0.68, 95% CI 0.48–0.95), but not statistically significant in those with CKD stage 1–3A (OR 0.97, 95% CI 0.68–1.38). The effect of statins was significant in patients with proteinuria ≥1000 mg/day (OR 0.63, 95% CI 0.43–0.92), but not statistically significant in those with proteinuria <1000 mg/day (OR 1.02, 95% CI 0.74–1.41).
Evolution of Glassy Carbon Microstructure: In Situ Transmission Electron Microscopy of the Pyrolysis Process
Authors: Sharma Swati , Shyam Kumar C. N. , Korvink Jan G. , Kübel Christian 
Published: October 2018

AbstractGlassy carbon is a graphene-rich form of elemental carbon obtained from pyrolysis of polymers, which is composed of three-dimensionally arranged, curved graphene fragments alongside fractions of disordered carbon and voids. Pyrolysis encompasses gradual heating of polymers at ≥ 900 °C under inert atmosphere, followed by cooling to room temperature. Here we report on an experimental method to perform in situ high-resolution transmission electron microscopy (HR-TEM) for the direct visualization of microstructural evolution in a pyrolyzing polymer in the 500–1200 °C temperature range. The results are compared with the existing microstructural models of glassy carbon. Reported experiments are performed at 80 kV acceleration voltage using MEMS-based heating chips as sample substrates to minimize any undesired beam-damage or sample preparation induced transformations. The outcome suggests that the geometry, expansion and atomic arrangement within the resulting graphene fragments constantly change, and that the intermediate structures provide important cues on the evolution of glassy carbon. A complete understanding of the pyrolysis process will allow for a general process tuning specific to the precursor polymer for obtaining glassy carbon with pre-defined properties.