bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optical clumped isotope thermometry of carbon dioxide
Authors: Prokhorov Ivan , Kluge Tobias , Janssen Christof 
Published: March 2019

AbstractSimultaneous analysis of carbon dioxide isotopologues involved in the isotope exchange between the doubly substituted 13C16O18O molecule and 12C16O2 has become an exciting new tool for geochemical, atmospheric and paleoclimatic research with applications ranging from stratospheric chemistry to carbonate-based geothermometry studies. Full exploitation of this isotope proxy and thermometer is limited due to time consuming and costly analysis using mass spectrometric instrumentation. Here, we present an all optical clumped CO2 isotopologue thermometer with capability for rapid analysis and simplified sample preparation. The current development also provides the option for analysis of additional multiply-substituted isotopologues, such as 12C18O2. Since the instrument unambiguously measures all isotopologues of the 12C16O2 + 13C16O18O $$\rightleftharpoons $$⇌ 13C16O2 + 12C16O18O exchange, its equilibrium constant and the corresponding temperature are measured directly. Being essentially independent of the isotope composition of the calibration gas, an uncalibrated working reference is sufficient and usage of international calibration standards is obsolete. Other isotopologues and molecules can be accessed using the methodology, opening up new avenues in isotope research. Here we demonstrate the high-precision performance of the instrument with first gas temperature measurements of carbon dioxide samples from geothermal sources.
Profiling of gallbladder carcinoma reveals distinct miRNA profiles and activation of STAT1 by the tumor suppressive miRNA-145-5p
Authors: Goeppert Benjamin , Truckenmueller Felicia , Ori Alessandro , Fritz Valerie , Albrecht Thomas , Fraas Angelika , Scherer Dominique , Silos Rosa González , Sticht Carsten , Gretz Norbert , Mehrabi Arianeb , Bewerunge-Hudler Melanie , Pusch Stefan , Bermejo Justo Lorenzo , Dietrich Peter , Schirmacher Peter , Renner Marcus , Roessler Stephanie 
Published: March 2019

AbstractGallbladder carcinoma (GBC) is a biliary tract cancer with few treatment options and poor prognosis. Radical surgery is the only potentially curative treatment option but most patients diagnosed with GBC are unresectable. Thus, there is a great need for the development of new treatment options including targeted therapy. Here, we aimed at identifying deregulated miRNAs and affected pathways involved in GBC development and progression. We performed global miRNA profiling of 40 GBC and 8 normal gallbladder tissues and identified large differences with 30% of miRNAs being differentially expressed (false discovery rate: FDR < 0.001). We found 24 miRNAs to be differentially regulated in GBC with poor outcome (p < 0.05) of which miR-145-5p was the most downregulated miRNA. Overexpression of miR-145-5p significantly reduced cell proliferation and colony formation. Gene expression analysis of cells expressing miR-145-5p mimics revealed activation of the Signal transducer and activator of transcription 1 (STAT1) signaling pathway which is mainly tumor suppressive. Furthermore, the activation of STAT1 by miR-145-5p was specifically observed in gallbladder carcinoma and cholangiocarcinoma but not in hepatocellular carcinoma cells. The Protein Tyrosine Phosphatase Receptor Type F (PTPRF) is downregulated upon miR-145 expression and may be involved in STAT1 regulation. In addition, we found that the STAT1-regulated protein IRF7 is downregulated in GBC compared to normal gallbladder tissue and low IRF7 expression is associated with significantly lower overall survival of GBC patients. Thus, this study identified GBC patient subgroups and provides new mechanistic insights in the tumor suppressive function of miR-145-5p leading to activation of STAT1 signaling.
The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux
Authors: Cavaliere Federica , Fornarelli Alessandra , Bertan Fabio , Russo Rossella , Marsal-Cots Anaïs , Morrone Luigi Antonio , Adornetto Annagrazia , Corasaniti Maria Tiziana , Bano Daniele , Bagetta Giacinto , Nicotera Pierluigi 
Published: March 2019

AbstractAntidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes. In this regard, it was previously demonstrated that clomipramine, a widely used FDA-approved tricyclic antidepressant, interferes with the autophagic flux and severely compromises the viability of tumorigenic cells upon cytotoxic stress. Consistent with this line of evidence, we report here that clomipramine undermines autophagosome formation and cargo degradation in primary dissociated neurons. A similar pattern was observed in the frontal cortex and liver of treated mice, as well as in the nematode Caenorhabditis elegans exposed to clomipramine. Together, our findings indicate that clomipramine may negatively regulate the autophagic flux in various tissues, with potential metabolic and functional implications for the homeostatic maintenance of differentiated cells.
Distinct triterpene synthases in the laticifers of Euphorbia lathyris
Authors: Forestier Edith , Romero-Segura Carmen , Pateraki Irini , Centeno Emilio , Compagnon Vincent , Preiss Myriam , Berna Anne , Boronat Albert , Bach Thomas J. , Darnet Sylvain , Schaller Hubert 
Published: March 2019

AbstractEuphorbia lathyriswas proposed about fifty years ago as a potential agroenergetic crop. The tremendous amounts of triterpenes present in its latex has driven investigations for transforming this particular biological fluid into an industrial hydrocarbon source. The huge accumulation of terpenes in the latex of many plant species represent a challenging question regarding cellular homeostasis. In fact, the enzymes, the mechanisms and the controllers that tune the amount of products accumulated in specialized compartments (to fulfill ecological roles) or deposited at important sites (as essential factors) are not known. Here, we have isolated oxidosqualene cyclases highly expressed in the latex ofEuphorbia lathyris. This triterpene biosynthetic machinery is made of distinct paralogous enzymes responsible for the massive accumulation of steroidal and non-steroidal tetracyclic triterpenes. More than eighty years after the isolation of butyrospermol from shea butter (Heilbronn IM, Moffet GL, and Spring FSJ.Chem.Soc. 1934, 1583), a butyrospermol synthase is characterized in this work using yeast andin foliaheterologous expression assays.
Simulations of Protein Adsorption on Nanostructured Surfaces
Authors: Manzi Berardo M. , Werner Marco , Ivanova Elena P. , Crawford Russell J. , Baulin Vladimir A. 
Published: March 2019

AbstractRecent technological advances have allowed the development of a new generation of nanostructured materials, such as those displaying both mechano-bactericidal activity and substrata that favor the growth of mammalian cells. Nanomaterials that come into contact with biological media such as blood first interact with proteins, hence understanding the process of adsorption of proteins onto these surfaces is highly important. The Random Sequential Adsorption (RSA) model for protein adsorption on flat surfaces was modified to account for nanostructured surfaces. Phenomena related to the nanofeature geometry have been revealed during the modelling process; e.g., convex geometries can lead to lower steric hindrance between particles, and hence higher degrees of surface coverage per unit area. These properties become more pronounced when a decrease in the size mismatch between the proteins and the surface nanostructures occurs. This model has been used to analyse the adsorption of human serum albumin (HSA) on a nano-structured black silicon (bSi) surface. This allowed the Blocking Function (the rate of adsorption) to be evaluated. The probability of the protein to adsorb as a function of the occupancy was also calculated.
Dual-FRET imaging of IP3 and Ca2+ revealed Ca2+-induced IP3 production maintains long lasting Ca2+ oscillations in fertilized mouse eggs
Authors: Matsu-ura Toru , Shirakawa Hideki , Suzuki Kenichi G. N. , Miyamoto Akitoshi , Sugiura Kotomi , Michikawa Takayuki , Kusumi Akihiro , Mikoshiba Katsuhiko 
Published: March 2019

AbstractIn most species, fertilization induces Ca2+ transients in the egg. In mammals, the Ca2+ rises are triggered by phospholipase Cζ (PLCζ) released from the sperm; IP3 generated by PLCζ induces Ca2+ release from the intracellular Ca2+ store through IP3 receptor, termed IP3-induced Ca2+ release. Here, we developed new fluorescent IP3 sensors (IRIS-2s) with the wider dynamic range and higher sensitivity (Kd = 0.047–1.7 μM) than that we developed previously. IRIS-2s employed green fluorescent protein and Halo-protein conjugated with the tetramethylrhodamine ligand as fluorescence resonance energy transfer (FRET) donor and acceptor, respectively. For simultaneous imaging of Ca2+ and IP3, using IRIS-2s as the IP3 sensor, we developed a new single fluorophore Ca2+ sensor protein, DYC3.60. With IRIS-2s and DYC3.60, we found that, right after fertilization, IP3 concentration ([IP3]) starts to increase before the onset of the first Ca2+ wave. [IP3] stayed at the elevated level with small peaks followed after Ca2+ spikes through Ca2+ oscillations. We detected delays in the peak of [IP3] compared to the peak of each Ca2+ spike, suggesting that Ca2+-induced regenerative IP3 production through PLC produces small [IP3] rises to maintain [IP3] over the basal level, which results in long lasting Ca2+ oscillations in fertilized eggs.
Historical BCG vaccination combined with drug treatment enhances inhibition of mycobacterial growth ex vivo in human peripheral blood cells
Authors: Prabowo Satria A. , Zelmer Andrea , Stockdale Lisa , Ojha Utkarsh , Smith Steven G. , Seifert Karin , Fletcher Helen A. 
Published: March 2019

AbstractTuberculosis (TB) is a leading infectious cause of death globally. Drug treatment and vaccination, in particular with Bacillus Calmette-Guérin (BCG), remain the main strategies to control TB. With the emergence of drug resistance, it has been proposed that a combination of TB vaccination with pharmacological treatment may provide a greater therapeutic value. We implemented an ex vivo mycobacterial growth inhibition assay (MGIA) to discriminate vaccine responses in historically BCG-vaccinated human volunteers and to assess the contribution of vaccine-mediated immune response towards the killing effect of mycobacteria in the presence of the antibiotics isoniazid (INH) and rifampicin (RIF), in an attempt to develop the assay as a screening tool for therapeutic TB vaccines. BCG vaccination significantly enhanced the ability of INH to control mycobacterial growth ex vivo. The BCG-vaccinated group displayed a higher production of IFN-γ and IP-10 when peripheral blood mononuclear cells (PBMC) were co-cultured with INH, with a similar trend during co-culture with RIF. A higher frequency of IFN-γ+ and TNF-α+ CD3− CD4− CD8− cells was observed, suggesting the contribution of Natural Killer (NK) cells in the combined effect between BCG vaccination and INH. Taken together, our data indicate the efficacy of INH can be augmented following historical BCG vaccination, which support findings from previous observational and animal studies.
Spin Torque Efficiency and Analytic Error Rate Estimates of Skyrmion Racetrack Memory
Authors: Suess Dieter , Vogler Christoph , Bruckner Florian , Heistracher Paul , Slanovc Florian , Abert Class 
Published: March 2019

AbstractIn this paper, the thermal stability of skyrmion bubbles and the critical currents to move them over pinning sites were investigated. For the used pinning geometries and the used parameters, the unexpected behavior is reported that the energy barrier to overcome the pinning site is larger than the energy barrier of the annihilation of a skyrmion. The annihilation takes place at boundaries by current driven motion, as well as due to the excitation over energy barriers, in the absence of currents, without forming Bloch points. It is reported that the pinning sites, which are required to allow thermally stable bits, significantly increase the critical current densities to move the bits in skyrmion-like structures to aboutjcrit = 0.62 TA/m². The simulation shows that the applied spin transfer model predicts experimentally obtained critical currents to move stable skyrmions at room temperature well, which is in contrast to simulations based on spin orbit torque that predict significantly too low critical currents. By calculating the thermal stability, as well as the critical current, we can derive the spin torque efficiency η = ΔE/Ic = 0.19 kBT300/μA, which is in a similar range to the simulated spin torque efficiency of MRAM structures. Finally, it is shown that the stochastic depinning process of any racetrack-like device requires an extremely narrow depinning time distribution smaller than ~6% of the current pulse length to reach bit error rates smaller than 10−9.
Laue three dimensional neutron diffraction
Authors: Raventós Marc , Tovar Michael , Medarde Marisa , Shang Tian , Strobl Markus , Samothrakitis Stavros , Pomjakushina Ekaterina , Grünzweig Christian , Schmidt Søren 
Published: March 2019

AbstractThis article presents a measurement technique and data analysis tool to perform 3D grain distribution mapping and indexing of oligocrystalline samples using neutrons: Laue three-dimensional neutron diffraction (Laue3DND). The approach builds on forward modelling used for correlation and multiple fitting of the measured diffraction spots relative to individual grains. This enables not only to identify individual grains, but also their position and orientation in the sample. The feasibility and performance of the Laue3DND approach are tested using multi-grain synthetic datasets from cubic (α-Fe) and tetragonal (YBaCuFeO5) symmetries. Next, experimental results from two data sets measured at the FALCON instrument of Helmholtz-Zentrum Berlin are presented: A cylindrical alpha iron (α-Fe) reference sample with 5 mm diameter and 5 mm height, as well as a 2 mm3layered perovskite (YBaCuFeO5). Using Laue3DND, we were able to retrieve the position and orientation of 97 out of 100 grains from a syntheticα-Fe data set, as well as 24 and 9 grains respectively from theα-Fe and YBaCuFeO5sample measured at FALCON. Results from the synthetic tests also indicate that Laue3DND is capable of indexing 10 out of 10 grains for both symmetries in two extreme scenarios: using only 6 Laue projections and using 360 projections with extremely noisy data. The precision achieved in terms of spatial and orientation resolution for the current version of the method is 430 μm and 1° respectively. Based on these results obtained, we are confident to present a tool that expands the capabilities of standard Laue diffraction, providing the number, position, orientation and relative size of grains in oligocrystalline samples.
Definition of network types – Prediction of dough mechanical behaviour under shear by gluten microstructure
Authors: Lucas Isabelle , Petermeier Hannes , Becker Thomas , Jekle Mario 
Published: March 2019

AbstractThis study defines network types of wheat gluten to describe spatial arrangements of gluten networks in relation to dough mechanical behaviour. To achieve a high variety in gluten arrangements, ten specific and unspecific gluten-modifying agents in increasing concentrations were added to wheat dough. Gluten microstructure was visualized by confocal laser scanning microscopy and quantified by protein network analysis. Dough rheological behaviour was determined by both oscillatory and creep-recovery tests. Based on correlation matrices and principal component analysis, six different network types were identified and associated to their rheological characteristics: a cleaved (low viscous), rigid (highly viscous), spread (viscoelastic), strengthened (viscoelastic), particulate and dense (highly viscous) or particulate and loose (low viscous) network. Furthermore, rheological dough properties of specifically gluten-modified samples were predicted with five microstructural gluten attributes (lacunarity, branching rate, end-point rate, protein width, average protein length) and assigned properly by the obtained partial least square model with an accuracy up to 90% (e.g., R2Y = 0.84 for G*, 0.85 for tanδ, 0.90 for Jmax). As a result, rheological properties of wheat doughs were predicted from microstructural investigations. This novel, quantitative definition of the relation between structure and mechanical behaviour can be used for developments of new wheat products with targeted properties.
Activity and structural analysis of GRL-117C: a novel small molecule CCR5 inhibitor active against R5-tropic HIV-1s
Authors: Nakata Hirotomo , Maeda Kenji , Das Debananda , Chang Simon B. , Matsuda Kouki , Rao Kalapala Venkateswara , Harada Shigeyoshi , Yoshimura Kazuhisa , Ghosh Arun K. , Mitsuya Hiroaki 
Published: March 2019

AbstractCCR5 is a member of the G-protein coupled receptor family that serves as an essential co-receptor for cellular entry of R5-tropic HIV-1, and is a validated target for therapeutics against HIV-1 infections. In the present study, we designed and synthesized a series of novel small CCR5 inhibitors and evaluated their antiviral activity. GRL-117C inhibited the replication of wild-type R5-HIV-1 with a sub-nanomolar IC50 value. These derivatives retained activity against vicriviroc-resistant HIV-1s, but did not show activity against maraviroc (MVC)-resistant HIV-1. Structural modeling indicated that the binding of compounds to CCR5 occurs in the hydrophobic cavity of CCR5 under the second extracellular loop, and amino acids critical for their binding were almost similar with those of MVC, which explains viral cross-resistance with MVC. On the other hand, one derivative, GRL-10018C, less potent against HIV-1, but more potent in inhibiting CC-chemokine binding, occupied the upper region of the binding cavity with its bis-THF moiety, presumably causing greater steric hindrance with CC-chemokines. Recent studies have shown additional unique features of certain CCR5 inhibitors such as immunomodulating properties and HIV-1 latency reversal properties, and thus, continuous efforts in developing new CCR5 inhibitors with unique binding profiles is necessary.
Risk Factors for Delayed Isolation of Patients with Active Pulmonary Tuberculosis in an Acute-care Hospital
Authors: Han Jaijun , Nam Bo Da , Park Se Yoon , Park Jebyung , Lee Eunyoung , Lee Eun Jung , Hwang Jung Hwa , Kim Tae Hyong 
Published: March 2019

AbstractThe objective of the current study was to determine the factors associated with delayed isolation of pulmonary tuberculosis (TB). In this retrospective study, data of patients newly diagnosed with pulmonary TB from January 2015 through December 2017 at a referral hospital were reviewed. Delayed recognition of pulmonary TB was defined as failure to initiate airborne isolation within the first 3 days of admission. We analyzed the clinical, microbiological, and radiological factors associated with delayed isolation of pulmonary TB. A total of 134 patients with positive sputum acid-fast bacilli (AFB) cultures were analyzed, of which 44 (33%) were isolated within 3 days after admission. In multivariate logistic regression analysis, older age (p = 0.01), admission to departments other than Infectious Disease or Pulmonology (p = 0.005), and presence of malignancy (p = 0.02) were associated with delayed isolation. Patients with a radiologic diagnosis of active pulmonary TB were likely to be isolated early (p = 0.01). Better awareness of pulmonary TB among attending practitioners in hospital settings is required. Delay in isolation is associated with older age, malignancy, hospitalization to departments other than Infectious Disease or Pulmonology, and non-confident radiologic diagnosis of active pulmonary TB.
Unbalanced calcium channel activity underlies selective vulnerability of nigrostriatal dopaminergic terminals in Parkinsonian mice
Authors: Sgobio Carmelo , Sun Lixin , Ding Jinhui , Herms Jochen , Lovinger David M. , Cai Huaibin 
Published: March 2019

AbstractDopamine (DA) release in striatum is functionally segregated across a dorsolateral/ventromedial axis. Interestingly, nigrostriatal DA signaling disruption in Parkinson’s disease (PD) preferentially affects the dorsolateral striatum. The relationship between afferent presynaptic calcium transients (PreCaTs) in DA terminals and DA release in dorsolateral (Caudato-Putamen, DLS) and ventromedial (Nucleus Accumbens Shell, VS) striatal subregions was examined by ex vivo real-time dual-recording in conditional transgenic mice expressing the calcium indicator protein GCaMP3. In DLS, minimal increases in cytosolic calcium trigger steep DA release while PreCaTs and DA release in VS both were proportional to the number of pulses in burst stimulation. Co-expressing α-synuclein with the Parkinson’s disease (PD)-associated A53T mutation and GCaMP3 in midbrain DA neurons revealed augmented cytosolic steady state and activity-dependent intra-terminal calcium levels preferentially in DLS, as well as hyperactivation and enhanced expression of N-type calcium channels. Thus, unbalanced calcium channel activity is a presynaptic mechanism to consider in the multifaceted pathogenic pathways of progressive neurodegeneration.
Reconstructing foot-and-mouth disease outbreaks: a methods comparison of transmission network models
Authors: Firestone Simon M. , Hayama Yoko , Bradhurst Richard , Yamamoto Takehisa , Tsutsui Toshiyuki , Stevenson Mark A. 
Published: March 2019

AbstractA number of transmission network models are available that combine genomic and epidemiological data to reconstruct networks of who infected whom during infectious disease outbreaks. For such models to reliably inform decision-making they must be transparently validated, robust, and capable of producing accurate predictions within the short data collection and inference timeframes typical of outbreak responses. A lack of transparent multi-model comparisons reduces confidence in the accuracy of transmission network model outputs, negatively impacting on their more widespread use as decision-support tools. We undertook a formal comparison of the performance of nine published transmission network models based on a set of foot-and-mouth disease outbreaks simulated in a previously free country, with corresponding simulated phylogenies and genomic samples from animals on infected premises. Of the transmission network models tested, Lau’s systematic Bayesian integration framework was found to be the most accurate for inferring the transmission network and timing of exposures, correctly identifying the source of 73% of the infected premises (with 91% accuracy for sources with model support >0.80). The Structured COalescent Transmission Tree Inference provided the most accurate inference of molecular clock rates. This validation study points to which models might be reliably used to reconstruct similar future outbreaks and how to interpret the outputs to inform control. Further research could involve extending the best-performing models to explicitly represent within-host diversity so they can handle next-generation sequencing data, incorporating additional animal and farm-level covariates and combining predictions using Ensemble methods and other approaches.