bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy attenuates tubulointerstital fibrosis through regulating transforming growth factor-β and NLRP3 inflammasome signaling pathway
Authors: Nam Sun Ah , Kim Wan-Young , Kim Jin Won , Park Sang Hee , Kim Hong Lim , Lee Myung-Shik , Komatsu Masaaki , Ha Hunjoo , Lim Ji Hee , Park Cheol Whee , Yang Chul Woo , Kim Jin , Kim Yong Kyun 
Published: January 2019

AbstractRenal fibrosis is the final common pathway of various renal injuries and it leads to chronic kidney disease. Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death and proliferation. Cellular response during unilateral ureteral obstruction (UUO) is tubular segment specific. Thus the role of autophagy on renal tubulointerstitial fibrosis (TIF) after UUO may be different according to segment of nephron. The role of autophagy during UUO remains unclear especially in distal tubules. In this study, we investigated the role of autophagy in distal tubules on renal TIF using conditional knockout mice in which Atg7 was genetically ablated specifically in distal tubular epithelial cell (TEC). In green fluorescent protein (GFP)-LC3 transgenic mice, GFP-LC3 puncta was highly expressed in distal tubular cells of the obstructed kidneys after UUO. Genetic deletion of Atg7 specifically in distal TEC increased renal tubulointerstial fibrosis and epithelial-mesenchymal transition-like phenotype change after UUO through Smad4-dependent transforming growth factor (TGF)-β pathway. Distal tubule-specific autophagy-deficient mice increased the accumulation of damaged mitochondria and SQSTM1/p62-positive aggregates in the obstructed kidney and resulted in increased expression of NLRP3 inflammasome, interleukin (IL) 1-β and caspase-1. Distal TEC-specific Atg7 deletion enhanced apoptosis of TECs after UUO. In summary, our data showed that autophagy in distal TEC plays a protective role in development of renal tubulointerstial fibrosis through regulating the expression of TGF-β an IL1-β after UUO.
PD-1/PD-L1 checkpoint blockade harnesses monocyte-derived macrophages to combat cognitive impairment in a tauopathy mouse model
Authors: Rosenzweig Neta , Dvir-Szternfeld Raz , Tsitsou-Kampeli Afroditi , Keren-Shaul Hadas , Ben-Yehuda Hila , Weill-Raynal Pierre , Cahalon Liora , Kertser Alex , Baruch Kuti , Amit Ido , Weiner Assaf , Schwartz Michal 
Published: January 2019

AbstractAlzheimer’s disease (AD) is a heterogeneous disorder with multiple etiologies. Harnessing the immune system by blocking the programmed cell death receptor (PD)-1 pathway in an amyloid beta mouse model was shown to evoke a sequence of immune responses that lead to disease modification. Here, blocking PD-L1, a PD-1 ligand, was found to have similar efficacy to that of PD-1 blocking in disease modification, in both animal models of AD and of tauopathy. Targeting PD-L1 in a tau-driven disease model resulted in increased immunomodulatory monocyte-derived macrophages within the brain parenchyma. Single cell RNA-seq revealed that the homing macrophages expressed unique scavenger molecules including macrophage scavenger receptor 1 (MSR1), which was shown here to be required for the effect of PD-L1 blockade in disease modification. Overall, our results demonstrate that immune checkpoint blockade targeting the PD-1/PD-L1 pathway leads to modification of common factors that go awry in AD and dementia, and thus can potentially provide an immunotherapy to help combat these diseases.
Optimal Gaussian measurements for phase estimation in single-mode Gaussian metrology
Authors: Oh Changhun , Lee Changhyoup , Rockstuhl Carsten , Jeong Hyunseok , Kim Jaewan , Nha Hyunchul , Lee Su-Yong 
Published: January 2019

AbstractThe central issue in quantum parameter estimation is to find out the optimal measurement setup that leads to the ultimate lower bound of an estimation error. We address here a question of whether a Gaussian measurement scheme can achieve the ultimate bound for phase estimation in single-mode Gaussian metrology that exploits single-mode Gaussian probe states in a Gaussian environment. We identify three types of optimal Gaussian measurement setups yielding the maximal Fisher information depending on displacement, squeezing, and thermalization of the probe state. We show that the homodyne measurement attains the ultimate bound for both displaced thermal probe states and squeezed vacuum probe states, whereas for the other single-mode Gaussian probe states, the optimized Gaussian measurement cannot be the optimal setup, although they are sometimes nearly optimal. We then demonstrate that the measurement on the basis of the product quadrature operators $$\hat X\hat P + \hat P\hat X$$

X

̂

P

̂

+

P

̂

X

̂

, i.e., a non-Gaussian measurement, is required to be fully optimal.
Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease
Authors: Kim Ko Woon , Kwon Hunki , Kim Young-Eun , Yoon Cindy W. , Kim Yeo Jin , Kim Yong Bum , Lee Jong Min , Yoon Won Tae , Kim Hee Jin , Lee Jin San , Jang Young Kyoung , Kim Yeshin , Jang Hyemin , Ki Chang-Seok , Youn Young Chul , Shin Byoung-Soo , Bang Oh Young , Kim Gyeong-Moon , Chung Chin-Sang , Kim Seung Joo , Na Duk L. , Duering Marco , Cho Hanna , Seo Sang Won 
Published: January 2019

AbstractCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). We enrolled typical CADASIL patients (N = 11) and SVCI patients [with NOTCH3 variants (N = 15), without NOTCH3 variants (N = 101)]. To adjust the age difference, which reflects the known difference in clinical and radiologic courses between typical CADASIL patients and SVCI patients, we constructed a W-score of measurement for diffusion tensor image and cortical thickness. Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected). We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, FDR-corrected) than typical CADASIL patients. In this study, typical CADASIL and SVCI showed distinct anatomic vulnerabilities in the cortical and subcortical structures. However, there was no difference between SVCI with NOTCH3 variants and SVCI without NOTCH3 variants.
Accurate signal-source localization in brain slices by means of high-density microelectrode arrays
Authors: Obien Marie Engelene J. , Hierlemann Andreas , Frey Urs 
Published: January 2019

AbstractExtracellular recordings by means of high-density microelectrode arrays (HD-MEAs) have become a powerful tool to resolve subcellular details of single neurons in active networks grown from dissociated cells. To extend the application of this technology to slice preparations, we developed models describing how extracellular signals, produced by neuronal cells in slices, are detected by microelectrode arrays. The models help to analyze and understand the electrical-potential landscape in anin vitroHD-MEA-recording scenario based on point-current sources. We employed two modeling schemes, (i) a simple analytical approach, based on the method of images (MoI), and (ii) an approach, based on finite-element methods (FEM). We compared and validated the models with large-scale, high-spatiotemporal-resolution recordings of slice preparations by means of HD-MEAs. We then developed a model-based localization algorithm and compared the performance of MoI and FEM models. Both models provided accurate localization results and a comparable and negligible systematic error, when the point source was in saline, a condition similar to cell-culture experiments. Moreover, the relative random error in the x-y-z-localization amounted only up to 4.3% for z-distances up to 200 μm from the HD-MEA surface. In tissue, the systematic errors of both, MoI and FEM models were significantly higher, and a pre-calibration was required. Nevertheless, the FEM values proved to be closer to the tissue experimental results, yielding 5.2 μm systematic mean error, compared to 22.0 μm obtained with MoI. These results suggest that the medium volume or “saline height”, the brain slice thickness and anisotropy, and the location of the reference electrode, which were included in the FEM model, considerably affect the extracellular signal and localization performance, when the signal source is at larger distance to the array. After pre-calibration, the relative random error of the z-localization in tissue was only 3% for z-distances up to 200 μm. We then applied the model and related detailed understanding of extracellular recordings to achieve an electrically-guided navigation of a stimulating micropipette, solely based on the measured HD-MEA signals, and managed to target spontaneously active neurons in an acute brain slice for electroporation.
The flagellin of candidate live biotherapeutic Enterococcus gallinarum MRx0518 is a potent immunostimulant
Authors: Lauté-Caly Delphine L. , Raftis Emma J. , Cowie Philip , Hennessy Emma , Holt Amy , Panzica D. Alessio , Sparre Christina , Minter Beverley , Stroobach Eline , Mulder Imke E. 
Published: January 2019

AbstractMany links between gut microbiota and disease development have been established in recent years, with particular bacterial strains emerging as potential therapeutics rather than causative agents. In this study we describe the immunostimulatory properties ofEnterococcus gallinarumMRx0518, a candidate live biotherapeutic with proven anti-tumorigenic efficacy. Here we demonstrate that strain MRx0518 elicits a strong pro-inflammatory response in key components of the innate immune system but also in intestinal epithelial cells. Using a flagellin knock-out derivative and purified recombinant protein, MRx0518 flagellin was shown to be a TLR5 and NF-κB activator in reporter cells and an inducer of IL-8 production by HT29-MTX cells.E. gallinarumflagellin proteins display a high level of sequence diversity and the flagellin produced by MRx0518 was shown to be more potent than flagellin fromE. gallinarumDSM100110. Collectively, these data infer that flagellin may play a role in the therapeutic properties ofE. gallinarumMRx0518.
Effects of Dihydroartemisinin-Piperaquine Phosphate and Artemether-Lumefantrine on QTc Interval Prolongation
Authors: Funck-Brentano Christian , Bacchieri Antonella , Valentini Giovanni , Pace Silvia , Tommasini Silva , Voiriot Pascal , Ubben David , Duparc Stephan , Evene Eric , Felices Mathieu , Corsi Marco 
Published: January 2019

AbstractQT/QTc interval prolongation reflects delayed cardiac repolarization which can lead to Torsade de Pointes and sudden death. Many antimalarial drugs prolong QT/QTc interval. However, due to confounding factors in patients with malaria, the precise extent of this effect has been found to be highly variable among studies. We compared the effects of dihydroartemisinin-piperaquine phosphate (DHA-PQP) and artemether-lumefantrine (A-L) on QT interval duration in healthy volunteers. In this randomized, parallel groups, active moxifloxacin- and placebo-controlled study, prolongation of the QT/QTc interval following treatment with DHA-PQP in fasted and fed condition and A-L in fed state was investigated in healthy subjects (n = 287; Clinicaltrials.gov: NCT01103830). DHA-PQP resulted in significant mean (95% confidence interval (CI)) maximum increases in QTc Fridericia (QTcF) of 21.0 ms (15.7, 26.4) for DHA-PQP fasted, 35.9 ms (31.1, 40.6) for DHA-PQP high-fat/low-caloric and 46.0 ms (39.6, 52.3) for DHA-PQP high-fat/high-caloric breakfast. For A-L, the largest difference from baseline relative to placebo was 9.9 ms (95% CI: 6.8, 12.9). Increases in QTcF related to maximum plasma concentrations of piperaquine. Moxifloxacin demonstrated assay sensitivity. Increases in QTcF following DHA-PQP and A-L were clinically relevant. Food increased piperaquine exposure and QTcF interval prolongation emphasizing the need to administer DHA-PQP in the fasting state.
RgsD negatively controls development, toxigenesis, stress response, and virulence in Aspergillus fumigatus
Authors: Kim Young , Lee Min-Woo , Jun Sang-Cheol , Choi Yong-Ho , Yu Jae-Hyuk , Shin Kwang-Soo 
Published: January 2019

AbstractThe regulator of G protein signaling (RGS) domain proteins generally attenuate heterotrimeric G protein signaling, thereby fine-tune the duration and strength of signal transduction. In this study, we characterize the functions of RgsD, one of the six RGS domain proteins present in the human pathogenic fungus Aspergillus fumigatus. The deletion (Δ) of rgsD results in enhanced asexual sporulation coupled with increased mRNA levels of key developmental activators. Moreover, ΔrgsD leads to increased spore tolerance to UV and oxidative stress, which might be associated with the enhanced expression of melanin biosynthetic genes and increased amount of melanin. Yeast two-hybrid assays reveal that RgsD can interact with the three Gα proteins GpaB, GanA, and GpaA, showing the highest interaction potential with GpaB. Importantly, the ΔrgsD mutant shows elevated expression of genes in the cAMP-dependent protein kinase A (PKA) pathway and PKA catalytic activity. The ΔrgsD mutant also display increased gliotoxin production and elevated virulence toward Galleria mellonella wax moth larvae. Transcriptomic analyses using RNA-seq reveal the expression changes associated with the diverse phenotypic outcomes caused by ΔrgsD. Collectively, we conclude that RgsD attenuates cAMP-PKA signaling pathway and negatively regulates asexual development, toxigenesis, melanin production, and virulence in A. fumigatus.
Study of CuO Nanowire Growth on Different Copper Surfaces
Authors: Fritz-Popovski Gerhard , Sosada-Ludwikowska Florentyna , Köck Anton , Keckes Jozef , Maier Günther A. 
Published: January 2019

AbstractCupric oxide (CuO) nanowires were produced by thermal oxidation of copper surfaces at temperatures up to 450 °C. Three different surfaces, namely a copper foil as well as evaporation deposited copper and an application relevant sputtered copper film on Si(100) substrates were characterized ex-situ before and after the experiment. The development of oxide layers and nanowires were monitored in-situ using grazing incidence small angle X-ray scattering. The number density of nanowires is highest for the sputtered surface and lowest for the surface prepared by evaporation deposition. This can be linked to different oxide grain sizes and copper grain boundary diffusions on the different surfaces. Small grains of the copper substrate and high surface roughness thereby lead to promoted growth of the nanowires.
Rosemary (Rosmarinus officinalis) extract causes ROS-induced necrotic cell death and inhibits tumor growth in vivo
Authors: Pérez-Sánchez Almudena , Barrajón-Catalán Enrique , Ruiz-Torres Verónica , Agulló-Chazarra Luz , Herranz-López María , Valdés Alberto , Cifuentes Alejandro , Micol Vicente 
Published: January 2019

AbstractColorectal cancer is the third most common diagnosed cancer globally. Although substantial advances have been obtained both in treatment and survival rates, there is still a need for new therapeutical approaches. Natural compounds are a realistic source of new bioactive compounds with anticancer activity. Among them, rosemary polyphenols have shown a vast antiproliferative capacity against colon cancer cells in vitro and in animal models. We have investigated the antitumor activity of a rosemary extract (RE) obtained by using supercritical fluid extraction through its capacity to inhibit various signatures of cancer progression and metastasis such as proliferation, migration, invasion and clonogenic survival. RE strongly inhibited proliferation, migration and colony formation of colon cancer cells regardless their phenotype. Treatment with RE led to a sharp increase of intracellular ROS that resulted in necrosis cell death. Nrf2 gene silencing increased RE cytotoxic effects, thus suggesting that this pathway was involved in cell survival. These in vitro results were in line with a reduction of tumor growth by oral administration of RE in a xenograft model of colon cancer cells using athymic nude mice. These findings indicate that targeting colon cancer cells by increasing intracellular ROS and decreasing cell survival mechanisms may suppose a therapeutic option in colon cancer through the combination of rosemary compounds and chemotherapeutic drugs.
Formation of environmentally stable hole-doped graphene films with instantaneous and high-density carrier doping via a boron-based oxidant
Authors: Kanahashi Kaito , Tanaka Naoki , Shoji Yoshiaki , Maruyama Mina , Jeon Il , Kawahara Kenji , Ishihara Masatou , Hasegawa Masataka , Ohta Hiromichi , Ago Hiroki , Matsuo Yutaka , Okada Susumu , Fukushima Takanori , Takenobu Taishi 
Published: February 2019

AbstractLarge-area graphene films have substantial potential for use as next-generation electrodes because of their good chemical stability, high flexibility, excellent carrier mobility, and lightweight structure. However, various issues remain unsolved. In particular, high-density carrier doping within a short time by a simple method, and air stability of doped graphene films, are highly desirable. Here, we demonstrate a solution-based high-density (>1014 cm−2) hole doping approach that promises to push the performance limit of graphene films. The reaction of graphene films with a tetrakis(pentafluorophenyl)borate salt, containing a two-coordinate boron cation, achieves doping within an extremely short time (4 s), and the doped graphene films are air stable for at least 31 days. X-ray photoelectron spectroscopy reveals that the graphene films are covered by the chemically stable anions, resulting in an improved stability in air. Moreover, the doping reduces the transmittance by only 0.44 ± 0.23%. The simplicity of the doping process offers a viable route to the large-scale production of functional graphene electrodes.
Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation
Authors: Diesch Jeannine , Bywater Megan J. , Sanij Elaine , Cameron Donald P. , Schierding William , Brajanovski Natalie , Son Jinbae , Sornkom Jirawas , Hein Nadine , Evers Maurits , Pearson Richard B. , McArthur Grant A. , Ganley Austen R. D. , O’Sullivan Justin M. , Hannan Ross D. , Poortinga Gretchen 
Published: January 2019

AbstractThe three-dimensional organization of the genome contributes to its maintenance and regulation. While chromosomal regions associate with nucleolar ribosomal RNA genes (rDNA), the biological significance of rDNA-genome interactions and whether they are dynamically regulated during disease remain unclear. rDNA chromatin exists in multiple inactive and active states and their transition is regulated by the RNA polymerase I transcription factor UBTF. Here, using a MYC-driven lymphoma model, we demonstrate that during malignant progression the rDNA chromatin converts to the open state, which is required for tumor cell survival. Moreover, this rDNA transition co-occurs with a reorganization of rDNA-genome contacts which correlate with gene expression changes at associated loci, impacting gene ontologies including B-cell differentiation, cell growth and metabolism. We propose that UBTF-mediated conversion to open rDNA chromatin during malignant transformation contributes to the regulation of specific gene pathways that regulate growth and differentiation through reformed long-range physical interactions with the rDNA.
Cupric-superoxide complex that induces a catalytic aldol reaction-type C–C bond formation
Authors: Abe Tsukasa , Hori Yuta , Shiota Yoshihito , Ohta Takehiro , Morimoto Yuma , Sugimoto Hideki , Ogura Takashi , Yoshizawa Kazunari , Itoh Shinobu 
Published: February 2019

AbstractMuch recent attention has been focused on the structure and reactivity of transition-metal superoxide complexes, among which mononuclear copper(II)-superoxide complexes are recognized as key reactive intermediates in many biological and abiological dioxygen-activation processes. So far, several types of copper(II)-superoxide complexes have been developed and their electrophilic reactivity has been explored in C–H and O–H bond activation reactions. Here we demonstrate that a mononuclear copper(II)-(end-on)superoxide complex supported by a N-[(2-pyridyl)methyl]-1,5-diazacyclooctane tridentate ligand can induce catalytic C–C bond formation reaction between carbonyl compounds (substrate) and the solvent molecule (acetone), giving β-hydroxy-ketones (aldol). Kinetic and spectroscopic studies at low temperature as well as DFT calculation studies support a nucleophilic reactivity of the superoxide species toward the carbonyl compounds, providing new insights into the reactivity of transition-metal superoxide species not only in biological oxidation reactions but also in synthetic organic chemistry.
A case study for the formation of stanene on a metal surface
Authors: Maniraj M. , Stadtmüller B. , Jungkenn D. , Düvel M. , Emmerich S. , Shi W. , Stöckl J. , Lyu L. , Kollamana J. , Wei Z. , Jurenkow A. , Jakobs S. , Yan B. , Steil S. , Cinchetti M. , Mathias S. , Aeschlimann M. 
Published: February 2019

AbstractThe discovery and realization of graphene as an ideal two-dimensional (2D) material has triggered extensive efforts to create similar 2D materials with exciting spin-dependent properties. Here, we report on a novel Sn 2D superstructure on Au(111) that shows similarities and differences to the expected electronic features of ideal stanene. Using spin- and angle-resolved photoemission spectroscopy, we find that a particular Sn/Au superstructure reveals a linearly dispersing band centered at the$${\bar{\mathrm \Gamma }}$$Γ¯-point and below the Fermi level with anti-parallel spin polarization and a Fermi velocity ofvF≈ 1×106m/s, the same value as for graphene. We attribute the origin of the band structure to the hybridization between the Sn and the Au orbitals at the 2D Sn-Au interface. Considering that free-standing stanene simply cannot exist, our investigated structure is an important step towards the search of useful stanene-like overstructures for future technological applications.
RDS(on) vs. inductance: comparison of SiC MOSFETs in 7pin D2Pak and 4pin TO‐247 and their benefits for high‐power MHz inverters
Authors: Denk Fabian , Haehre Karsten , Eizaguirre Cabrera Santiago , Simon Christoph , Heidinger Michael , Kling Rainer , Heering Wolfgang 
Published: February 2019

In this work, the authors present their investigations of the benefits of combining the latest silicon carbide MOSFETs with novel packages for electronic ballasts of inductively coupled plasmas. Such plasmas require MHz inverters with output powers above 2 kW. Additionally, for a breakthrough of the technology efficiencies >90% have to be realised. It has been shown that a combination is achievable with SiC FETs. Nevertheless, even though the transistors have undergone significant development in recent years, one limiting factor has mostly remained untouched. The common TO‐247 package does not fit to the requirements of a fast switching application. Within the latest launch of the new generations of SiC MOSFETs, some are available in novel packages with kelvin source connection, like 4pin TO‐247 and 7pin D2Pak. The authors compare three versions of the latest generation in a resonant full‐bridge inverter and in application‐oriented test. Thereby, the 7pin D2Pak and one of the 4pin TO‐247 transistors were 65 mΩ devices and the second 4pin TO‐247 FET was a 45 mΩ device. For the investigations, the authors made simulations, built three MHz inverters, and conducted measurements. Consequently, efficiencies of 93.9% could be achieved at a switching frequency of 2.5 MHz and an output power of Pout=2.6 kW.