bluuebunny/crossref_metadata_2025 huggingface dataset:
SREIS-D
Authors: Vöhringer Matthias , Schütz Astrid , Gessler Sarah , Schröder-Abé Michela
Published: May 2020

Zusammenfassung. Emotionale Intelligenz (EI) ist ein zentraler Prädiktor psychischer Gesundheit. Im deutschsprachigen Raum lag bislang keine am Vier-Facetten-Modell der EI orientierte Selbstbeschreibungsskala vor, die an klinischen und nicht-klinischen Gruppen getestet wurde. Die Self-Rated Emotional Intelligence Scale (SREIS) ist mit 19 Items ein ökonomisch einsetzbares Instrument. Die Skala wurde ins Deutsche übertragen und psychometrisch überprüft. Außerdem wurde die SREIS erstmals an einer klinischen Population getestet. Auch werden erstmals differenzierte Ergebnisse zu den vier EI-Facetten vorgelegt. Die Ergebnisse bestätigen die Faktorenstruktur der englischen Originalskala. Die Reliabilität der Gesamtskala ist als gut einzustufen. Validität wird durch erwartungskonforme Korrelationen mit anderen EI-Maßen sowie klinischen Parametern belegt. Durch Diskriminationsfähigkeit zwischen klinischer Stichprobe und nicht-klinischer Kontrollgruppe zeigt die Skala zusätzlich klinische Relevanz. Skalare Messinvarianz zwischen beiden Gruppen liegt vor. Die SREIS-D ist ein ökonomisch einsetzbares Selbstberichtsmaß zur Erfassung von Facetten der EI im klinischen und subklinischen Bereich.
Aligning Climate Models With Stakeholder Needs: Advances in Communicating Future Rainfall Uncertainties for South Florida Decision Makers
Authors: Infanti Johnna M. , Kirtman Ben P. , Aumen Nicholas G. , Stamm John , Polsky Colin
Published: May 2020

Changes in future precipitation are of great importance to climate data users in South Florida. A recent U.S. Geological Survey workshop, “Increasing Confidence in Precipitation Projections for Everglades Restoration,” highlighted a gap between standard climate model outputs and the climate information needs of some key Florida natural resource managers. These natural resource managers (hereafter broadly defined as “climate data users”) need more tailored output than is commonly provided by the climate modeling community. This study responds to these user needs by outlining and testing an adaptable methodology to select output from ensemble climate‐model simulations based on user‐defined precipitation drivers, using statistical methods common across scientific disciplines. This methodology is developed to provide a “decision matrix” that guides climate data users to specify the subset of models most important to their work based on each user's season (winter, summer, and annual) and the condition (dry, wet, neutral, and no threshold events) of interest. The decision matrix is intended to better communicate the subset of models best representing precipitation drivers. This information could increase users' confidence in climate models as a resource for natural resource planning and can be used to direct future dynamical downscaling efforts. This methodology is based in dynamical processes controlling precipitation via remote and local teleconnections. We also suggest that future climate studies in South Florida include high‐resolution climate model runs (i.e., ocean eddy resolving) in conjunction with dynamical downscaling to adequately capture precipitation variability.
Temperature‐Dependent Changes in the Normal Albedo of the Lunar Surface at 1,064 nm
Authors: Deutsch Ariel N. , Neumann Gregory A. , Head James W. , Lucey Paul G.
Published: May 2020

Over the extreme temperature variations experienced in a single lunar day (∆T ≈ 300 K), particular minerals common to the lunar surface show spectral changes at discrete near‐infrared wavelengths in laboratory settings (Roush & Singer, 1986, 1987, https://10.1111/10.1029/JB091iB10p10301, https://10.1111/10.1016/0019-1035(87)90026-1; Singer & Roush, 1985, https://10.1111/10.1029/JB090iB14p12434). Variations in temperature can cause variations in the size and shape of crystallographic sites, which control the position, shape, and depth of crystal field absorptions. At an observation wavelength of 1,064 nm, the Lunar Orbiter Laser Altimeter (LOLA) should be highly sensitive to temperature‐dependent changes of orthopyroxene. Here we analyze temperature‐dependent spectral changes of the lunar surface as measured from orbit by LOLA. We couple LOLA measurements of normal albedo with measurements of surface temperature from the Diviner Lunar Radiometer Experiment, analyzing the maria and highlands between ±50°. We provide the first evidence of temperature‐dependent spectral changes on the lunar surface from orbital observations, finding that the majority of the surface between ±50° demonstrates a small, yet measurable, negative change in 1,064‐nm albedo with temperature (−∆R/∆T). The measurable effect is on the order of a few percent change in reflectance per ~80 K, indicating that temperature changes do not have a large effect on measurements of albedo at the sensitivity of the LOLA instrument. Stronger −∆R/∆T values tend to be associated with regions with elevated orthopyroxene, and the maria typically have higher levels of orthopyroxene and stronger −∆R/∆T values than the highlands. Our results suggest that single‐wavelength lasers may be powerful tools for understanding the distribution of particular minerals on the lunar surface.
Relative Roles of Eurasian Snow Depth and Sea Surface Temperature in Indian and Korean Summer Monsoons Based on GME Model Simulations
Authors: Panda S. K. , Hong Mi‐Jin , Dash S. K. , Oh Jai‐Ho , Pattnayak K. C.
Published: May 2020

Indian Summer Monsoon (ISM) and East Asian Summer Monsoon (EASM) are the most important weather systems in India and Korea respectively. The interannual variations of ISM and EASM largely depend on the anomalies of sea surface temperatures (SSTs) of Tropical Equtorial Pacific and Indian Ocean and also on the Eurasian Snow Depth/Cover. In this study, the relative roles of these two most important surface boundary conditions on the Indian and Korean monsoons have been examined using the high resolution (40 km) global numerical weather prediction model of German Weather Service (GME). Four sets of experiments were carried out by varying the climatological and observed values of SSTs and snow. This study shows that there is a negative (positive) relationship between the Western (Eastern) Eurasian snow depth and ISMR, whereas a positive (negative) relationship between the Western (Eastern) Eurasian snow depth and Korean monsoon rainfall has been observed. Results show that when observed SST and snow are prescribed to the model as boundary conditions, the simulated winds and rainfall are close to the NCEP/NCAR reanalyzed winds and GPCP rainfall, respectively. This study reveals that the model simulated summer monsoons in Indian and Korean domains are not good enough unless an observed Eurasian snow is prescribed in addition to the observed SST.
Toward Understanding the Simulated Phase Partitioning of Arctic Single‐Layer Mixed‐Phase Clouds in E3SM
Authors: Zhang Meng , Xie Shaocheng , Liu Xiaohong , Lin Wuyin , Zhang Kai , Ma Hsi‐Yen , Zheng Xue , Zhang Yuying
Published: May 2020

Arctic mixed‐phase clouds simulated by the U.S. Department of Energy (DOE) Energy Exascale Earth System Model (E3SM) Atmosphere Model version 1 (EAMv1) are found to be overly dominated by supercooled liquid with little ice production. Sensitivity experiments using the short‐term hindcast approach are performed to isolate the impact of several new parameterizations on the simulated mixed‐phase clouds in EAMv1. These include the Classical Nucleation Theory (CNT) ice nucleation scheme, the Cloud Layer Unified By Binormals (CLUBB) parameterization, and the updated Morrison and Gettelman microphysics scheme (MG2). Results are compared to the DOE's Atmospheric Radiation Measurement (ARM) Mixed‐Phase Arctic Cloud Experiment (M‐PACE) observations. It is found that all of these new parameterizations are responsible for the decrease of cloud ice water content in EAMv1 simulated single‐layer mixed‐phase clouds. A budget analysis of detailed cloud microphysical processes suggests that a lack of initial ice particles from ice nucleation or convective detrainment strongly diminishes the cloud ice water content through the subsequent ice mass growth processes. Reduced heterogeneous ice nucleation by CNT at temperatures warmer than −15°C along with negligible ice processes in CLUBB are primarily responsible for the problem. Because the use of MG2 does not impact initial ice formation, the MG2 cloud microphysics is not the primary reason for the underestimate of cloud ice. However, using MG2 leads to a lower total ice mass due to a higher accretion rate of liquid droplets by rain drops and a lower ice mass growth rate.
A Model for Predicting Coastal Aerosol Size Distributions in Chinese Seas
Authors: Pan Yue , Cui Shengcheng , Rao Ruizhong
Published: May 2020

Aerosol is a key factor in the study of interactions between light and radiation. In coastal environments, the diversity and complexity of aerosol components make it difficult to accurately determine their microphysical and optical properties. In this paper, the analysis focuses on the aerosol size distribution (ASD) prediction in the coasts of the South China Sea (SCS, Maoming) and the Yellow Sea (YS, Qingdao). Due to large differences in spatial scale with respect to geographical and meteorological conditions, ASD in Maoming and Qingdao showed large differences. On the basis of Navy Aerosol Model (NAM) and Piazzola et al.'s models, combined with the observation data of Maoming and Qingdao, a coastal aerosol model (CAM) was developed to predict ASD for Chinese coastal environment. The aerosol concentration is calculated by the function of fetch and wind speed. Although the aerosol distributions at the two sites are quite different, the CAM is found to be applicable to both sites. Furthermore, the CAM was used in predicting the ASDs in the SCS against the research ship Shenkuo cruise data. The model results were in agreement with the measured values in coastal zone. The model presented in this work would be a useful tool to model ASDs in Chinese coastal seas.
Effects of Microphysical Processes on the Precipitation Spectrum in a Strongly Forced Environment
Authors: Huang Jin‐De , Wu Chien‐Ming
Published: May 2020

This study investigates the effects of microphysical processes on the precipitation spectrum in a strongly forced environment using the vector vorticity cloud‐resolving model (VVM). Experiments are performed under imposed advective cooling and moistening with two microphysics parameterizations: the predicted particle properties scheme (P3) and Lin scheme (VVM‐Lin). Even though the domain‐averaged precipitation is similar in the two experiments, P3 exhibits stronger extreme precipitation in the spectrum compared with VVM‐Lin. Changes in convective structures are responsible for such a difference. Using the isentropic analyses, we identify that in P3, stronger convective updrafts take place in the high θei regime, where air parcels rarely reach. This is caused by the reduced melting of rimed ice particles for energic parcels. Through defining convective core clouds, the relation between the convective structure on the isentropic diagram and the extreme precipitation can be identified. The shifts toward extreme intensity in the precipitation spectrum suggest that the microphysical processes have significant impacts on the extreme precipitation by the convective core clouds. The treatment of microphysics has significant impacts on the convective structures and then alter the probability of extreme events under the strongly forced environment.
Subsurface Structure at the InSight Landing Site From Compliance Measurements by Seismic and Meteorological Experiments
Authors: Kenda B. , Drilleau M. , Garcia R. F. , Kawamura T. , Murdoch N. , Compaire N. , Lognonné P. , Spiga A. , Widmer‐Schnidrig R. , Delage P. , Ansan V. , Vrettos C. , Rodriguez S. , Banerdt W. B. , Banfield D. , Antonangeli D. , Christensen U. , Mimoun D. , Mocquet A. , Spohn T.
Published: May 2020

Measurements of ground compliance at the InSight landing site—describing the surface response to pressure loading—are obtained from seismic and meteorological data. Compliance observations show an increase with frequency indicating the presence of a stiffer rock layer beneath the exposed regolith. We performed a Markov chain Monte Carlo inversion to investigate the vertical profile of the elastic parameters down to 20 m below InSight. Compliance was inverted both freely and assuming prior knowledge of compaction in the regolith, and the limitations and strengths of the methods were assessed on the basis of theoretical considerations and synthetic tests. The inverted Young modulus exhibits an increase by a factor of 10–100 over the first 10–15 m, compatible with a structural discontinuity between 0.7 and 7 m. The proposed scheme can be used for joint inversion of other seismic, geological, or mechanical constraints to refine the resulting vertical section.
Tanshinone IIA inhibits oral squamous cell carcinoma via reducing Akt-c-Myc signaling-mediated aerobic glycolysis
Authors: Li Ming , Gao Feng , Zhao Qing , Zuo Huilan , Liu Wenbin , Li Wei
Published: May 2020

Aerobic glycolysis is one of the hallmarks of human cancer cells. Overexpression of hexokinase 2 (HK2) plays a crucial role in the maintaining of unlimited tumor cell growth. In the present study, we found that the oral squamous cell carcinoma (OSCC) cells exhibited an aerobic glycolysis phenotype. Moreover, HK2 is highly expressed in OSCC patient derived-tissues and cell lines. Depletion of HK2 inhibited OSCC cell growth in vitro and in vivo. With a natural product screening, we identified Tanshinone IIA (Tan IIA) as a potential anti-tumor compound for OSCC through suppressing HK2-mediated glycolysis. Tan IIA decreased glucose consumption, lactate production, and promoted intrinsic apoptosis in OSCC cells. The mechanism study revealed that Tan IIA inhibited the Akt-c-Myc signaling and promoted E3 ligase FBW7-mediated c-Myc ubiquitination and degradation, which eventually reduced HK2 expression at the transcriptional level. In summary, these results indicate that targeting HK2-mediated aerobic glycolysis is a promising anti-tumor strategy for OSCC treatment.
Neutrophils undergo switch of apoptosis to NETosis during murine fatty liver injury via S1P receptor 2 signaling
Authors: Zhao Xinhao , Yang Le , Chang Na , Hou Lei , Zhou Xuan , Yang Lin , Li Liying
Published: May 2020

Inappropriate neutrophil infiltration and subsequent neutrophil extracellular trap (NET) formation have been confirmed to be involved in chronic inflammatory conditions. Fatty liver disease is an increasingly severe health problem worldwide and currently considered the most common cause of chronic liver disease. Sphingosine 1-phosphate (S1P), a product of membrane sphingolipid metabolism, regulates vital physiological and pathological actions by inducing infiltration and activation of various cell types through S1P receptors (S1PRs). Here, we seek to determine the S1PR-mediated effects on neutrophil activation during chronic liver inflammation. In this study, NETs are detected in the early stage of methionine-choline-deficient and a high-fat (MCDHF) diet-induced liver injury. NET depletion by deoxyribonuclease I intraperitoneal injection significantly protects liver from MCDHF-induced liver injury in vivo. Meanwhile, we show that levels of myeloperoxidase-DNA complex (NET marker) in the serum present positive correlation with sphingosine kinase1 (S1P rate-limiting enzyme) messenger RNA expression or S1P levels in the injured liver of MCDHF-fed mice. In vitro, S1PR2 participates in the redirection of neutrophil apoptosis to NETosis via Gαi/o, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and reactive oxygen species signaling pathways. Moreover, S1PR2 knockdown in MCDHF-fed mice by S1PR2-siRNA intravenous injection significantly inhibits NET formation in damaged liver tissue and then alleviates hepatic inflammation and fibrosis. Conclusion: In the early stage of fatty liver disease, S1PR2-mediated neutrophil activation plays an important role in the evolvement of liver injury.
BCL-xL/BCL2L1 is a critical anti-apoptotic protein that promotes the survival of differentiating pancreatic cells from human pluripotent stem cells
Authors: Loo Larry Sai Weng , Soetedjo Andreas Alvin Purnomo , Lau Hwee Hui , Ng Natasha Hui Jin , Ghosh Soumita , Nguyen Linh , Krishnan Vidhya Gomathi , Choi Hyungwon , Roca Xavier , Hoon Shawn , Teo Adrian Kee Keong
Published: May 2020

The differentiation of human pluripotent stem cells into pancreatic cells involves cellular proliferation and apoptosis during cell fate transitions. However, their implications for establishing cellular identity are unclear. Here, we profiled the expression of BCL-2 family of proteins during pancreatic specification and observed an upregulation of BCL-xL, downregulation of BAK and corresponding downregulation of cleaved CASP3 representative of apoptosis. Experimental inhibition of BCL-xL reciprocally increased apoptosis and resulted in a decreased gene expression of pancreatic markers despite a compensatory increase in anti-apoptotic protein BCL-2. RNA-Seq analyses then revealed a downregulation of multiple metabolic genes upon inhibition of BCL-xL. Follow-up bioenergetics assays revealed broad downregulation of both glycolysis and oxidative phosphorylation when BCL-xL was inhibited. Early perturbation of BCL-xL during pancreatic specification also had subsequent detrimental effects on the formation of INS+ pancreatic beta-like cells. In conclusion, the more differentiated pancreatic progenitors are dependent on anti-apoptotic BCL-xL for survival, whereas the less differentiated pancreatic progenitors that survived after WEHI-539 treatment would exhibit a more immature phenotype. Therefore, modulation of the expression level of BCL-xL can potentially increase the survival and robustness of pancreatic progenitors that ultimately define human pancreatic beta cell mass and function.
Functionally distinct high and low theta oscillations in the human hippocampus
Authors: Goyal Abhinav , Miller Jonathan , Qasim Salman E. , Watrous Andrew J. , Zhang Honghui , Stein Joel M. , Inman Cory S. , Gross Robert E. , Willie Jon T. , Lega Bradley , Lin Jui-Jui , Sharan Ashwini , Wu Chengyuan , Sperling Michael R. , Sheth Sameer A. , McKhann Guy M. , Smith Elliot H. , Schevon Catherine , Jacobs Joshua
Published: May 2020

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4–10 Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta’s function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior–posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.
Accurate deep neural network inference using computational phase-change memory
Authors: Joshi Vinay , Le Gallo Manuel , Haefeli Simon , Boybat Irem , Nandakumar S. R. , Piveteau Christophe , Dazzi Martino , Rajendran Bipin , Sebastian Abu , Eleftheriou Evangelos
Published: May 2020

In-memory computing using resistive memory devices is a promising non-von Neumann approach for making energy-efficient deep learning inference hardware. However, due to device variability and noise, the network needs to be trained in a specific way so that transferring the digitally trained weights to the analog resistive memory devices will not result in significant loss of accuracy. Here, we introduce a methodology to train ResNet-type convolutional neural networks that results in no appreciable accuracy loss when transferring weights to phase-change memory (PCM) devices. We also propose a compensation technique that exploits the batch normalization parameters to improve the accuracy retention over time. We achieve a classification accuracy of 93.7% on CIFAR-10 and a top-1 accuracy of 71.6% on ImageNet benchmarks after mapping the trained weights to PCM. Our hardware results on CIFAR-10 with ResNet-32 demonstrate an accuracy above 93.5% retained over a one-day period, where each of the 361,722 synaptic weights is programmed on just two PCM devices organized in a differential configuration.
Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor
Authors: Guan Chengcheng , Niu Yange , Chen Si-Cong , Kang Yunlu , Wu Jing-Xiang , Nishi Koji , Chang Catherine C. Y. , Chang Ta-Yuan , Luo Tuoping , Chen Lei
Published: May 2020

Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members.
Author Correction: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer
Authors: Färkkilä Anniina , Gulhan Doga C. , Casado Julia , Jacobson Connor A. , Nguyen Huy , Kochupurakkal Bose , Maliga Zoltan , Yapp Clarence , Chen Yu-An , Schapiro Denis , Zhou Yinghui , Graham Julie R. , Dezube Bruce J. , Munster Pamela , Santagata Sandro , Garcia Elizabeth , Rodig Scott , Lako Ana , Chowdhury Dipanjan , Shapiro Geoffrey I. , Matulonis Ursula A. , Park Peter J. , Hautaniemi Sampsa , Sorger Peter K. , Swisher Elizabeth M. , D’Andrea Alan D. , Konstantinopoulos Panagiotis A.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice
Authors: Yoshida Shota , Nakagami Hironori , Hayashi Hiroki , Ikeda Yuka , Sun Jiao , Tenma Akiko , Tomioka Hideki , Kawano Tomohiro , Shimamura Munehisa , Morishita Ryuichi , Rakugi Hiromi
Published: May 2020

Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4+ CD44high CD62Llow PD-1+ CD153+ cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) conjugate vaccine with Alhydrogel (CD153-Alum) or CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10–11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A complement-dependent cytotoxicity (CDC) assay indicated that the mouse IgG2 antibody produced in the CD153-CpG-vaccinated mice successfully reduced the number of senescent T cells. The CD153-CpG vaccine is an optional tool for senolytic therapy.
Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma
Authors: Thurner Lorenz , Hartmann Sylvia , Fadle Natalie , Regitz Evi , Kemele Maria , Kim Yoo-Jin , Bohle Rainer Maria , Nimmesgern Anna , von Müller Lutz , Kempf Volkhard A. J. , Weniger Marc A. , Neumann Frank , Schneider Nadine , Vornanen Martine , Sundström Christer , de Leval Laurence , Engert Andreas , Eichenauer Dennis A. , Küppers Ralf , Preuss Klaus-Dieter , Hansmann Martin-Leo , Pfreundschuh Michael
Published: May 2020

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta’ (RpoC) fromMoraxella catarrhalisas frequent antigen of BCRs of IgD+LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed byMoraxella catarrhalisthat is known to activate IgD+B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD+DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD+BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies.
The genome of Mekong tiger perch (Datnioides undecimradiatus) provides insights into the phylogenetic position of Lobotiformes and biological conservation
Authors: Sun Shuai , Wang Yue , Zeng Wenhong , Du Xiao , Li Lei , Hong Xiaoning , Huang Xiaoyun , Zhang He , Zhang Mengqi , Fan Guangyi , Liu Xin , Liu Shanshan
Published: May 2020

Mekong tiger perch (Datnioides undecimradiatus) is an ornamental and vulnerable freshwater fish native to the Mekong basin in Indochina, belonging to the order Lobotiformes. Here, we generated 121X stLFR co-barcode clean reads and 18X Oxford Nanopore MinION reads and obtained a 595 Mb Mekong tiger perch genome, which is the first whole genome sequence in the order Lobotiformes. Based on this genome, the phylogenetic tree analysis suggested that Lobotiformes is more closely related to Sciaenidae than to Tetraodontiformes, resolving a long-time dispute. We depicted the genes involved in pigment development in Mekong tiger perch and results confirmed that the four rate-limiting genes of pigment synthesis had been retained after fish-specific genome duplication. We also estimated the demographic history of Mekong tiger perch, which showed that the effective population size suffered a continuous reduction possibly related to the contraction of immune-related genes. Our study provided a reference genome resource for the Lobotiformes, as well as insights into the phylogenetic position of Lobotiformes and biological conservation.
Re-estimation improved the performance of two Framingham cardiovascular risk equations and the Pooled Cohort equations: A nationwide registry analysis
Authors: Wallisch Christine , Heinze Georg , Rinner Christoph , Mundigler Gerald , Winkelmayer Wolfgang C. , Dunkler Daniela
Published: May 2020

Equations predicting the risk of occurrence of cardiovascular disease (CVD) are used in primary care to identify high-risk individuals among the general population. To improve the predictive performance of such equations, we updated the Framingham general CVD 1991 and 2008 equations and the Pooled Cohort equations for atherosclerotic CVD within five years in a contemporary cohort of individuals who participated in the Austrian health-screening program from 2009–2014. The cohort comprised 1.7 M individuals aged 30–79 without documented CVD history. CVD was defined by hospitalization or death from cardiovascular cause. Using baseline and follow-up data, we recalibrated and re-estimated the equations. We evaluated the gain in discrimination and calibration and assessed explained variation. A five-year general CVD risk of 4.61% was observed. As expected, discrimination c-statistics increased only slightly and ranged from 0.73–0.79. The two original Framingham equations overestimated the CVD risk, whereas the original Pooled Cohort equations underestimated it. Re-estimation improved calibration of all equations adequately, especially for high-risk individuals. Half of the individuals were reclassified into another risk category using the re-estimated equations. Predictors in the re-estimated Framingham equations explained 7.37% of the variation, whereas the Pooled Cohort equations explained 5.81%. Age was the most important predictor.
Venturicidin A, A Membrane-active Natural Product Inhibitor of ATP synthase Potentiates Aminoglycoside Antibiotics
Authors: Yarlagadda Venkateswarlu , Medina Ricardo , Wright Gerard D.
Published: May 2020

Despite the remarkable advances due to the discovery and development of antimicrobials agents, infectious diseases remain the second leading cause of death worldwide. This fact underlines the importance of developing new therapeutic strategies to address the widespread antibiotic resistance, which is the major contributing factor for clinical failures of the current therapeutics. In a screen for antibiotic adjuvants, we identified a natural product from actinomycetes, venturicidin A (VentA), that potentiates the aminoglycoside antibiotic gentamicin against multidrug-resistant clinical isolates of Staphylococcus, Enterococcus, and Pseudomonas aeruginosa. Furthermore, the combination of gentamicin and VentA was bactericidal and rapidly eradicated methicillin-resistant S. aureus (MRSA). The molecular mechanism of gentamicin potentiation activity is attributed to uncoupling of ATP synthesis by VentA from electron transport presumably by blocking the proton flow through ATP synthase, which results in an elevated concentration of extracellular protons and subsequent anticipated raise in gentamicin uptake. The disruption of the proton flux was characterized by perturbed membrane potential in MRSA. These results demonstrate that inhibition of ATP synthase along with the subsequent membrane dysregulation, as shown here with VentA, complements aminoglycoside antibiotics against MDR bacteria, and that this approach may be employed to combat bacterial resistance.
Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer’s transgenic mice
Authors: Dodiya Hemraj B. , Frith Mary , Sidebottom Ashley , Cao Yajun , Koval Jason , Chang Eugene , Sisodia Sangram S.
Published: May 2020

In preceding efforts, we demonstrated that antibiotic (ABX) cocktail-mediated perturbations of the gut microbiome in two independent transgenic lines, termed APPSWE/PS1ΔE9 and APPPS1-21, leads to a reduction in Aβ deposition in male mice. To determine whether these observed reductions of cerebral Aβ amyloidosis are specific to any individual antibiotic or require the synergistic effects of several antibiotics, we treated male APPPS1-21 transgenic mice with either individual ABX or an ABX cocktail and assessed amyloid deposition. Specifically, mice were subject to oral gavage with high dose kanamycin, gentamicin, colistin, metronidazole, vancomycin, individually or in a combination (ABX cocktail) from postnatal days (PND) 14 to 21, followed by ad libitum, low-dose individual ABX or ABX cocktail in the drinking water until the time of sacrifice. A control group was subject to gavage with water from PND 14 to 21 and received drinking water till the time of sacrifice. At the time of sacrifice, all groups showed distinct cecal microbiota profiles with the highest differences between control and ABX cocktail-treated animals. Surprisingly, only the ABX cocktail significantly reduced brain Aβ amyloidosis compared to vehicle-treated animals. In parallel studies, and to assess the potential exposure of ABX to the brain, we quantified the levels of each ABX in the brain by liquid chromatography-mass spectrometry (LC-MS) at PND 22 or at 7 weeks of age. With the exception of metronidazole (which was observed at less than 3% relative to the spiked control brains), we were unable to detect the other individual ABX in brain homogenates. Our findings suggest that synergistic alterations of gut microbial consortia, rather than individual antimicrobial agents, underlie the observed reductions in brain amyloidosis.
HIV-1 Tat – TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway
Authors: Bahraoui Elmostafa , Serrero Manutea , Planès Rémi
Published: May 2020

In the present study we showed that HIV-1 Tat protein stimulated the expression of Indoleamine 2,3 dioxygenase (IDO) -1 in human monocytes derived dendritic cells (MoDC) but not IDO-2 by acting directly at the cell membrane level. This induction of IDO-1 is dependent on the secondary structure of Tat protein, since stimulation with a chemically oxidized Tat protein loses its capacity to induce the production of IDO-1. Among the variety of candidate receptors described for Tat, we demonstrated that Tat protein interacted physically with TLR4/MD2 complex. Strikingly, blockade of Tat-TLR4 interaction by anti-TLR4 antibodies (clone HTA125), LPS-RS, a known TLR4 antagonist, or by soluble recombinant TLR4/MD2 complex inhibited strongly or totally the capacity of Tat to induce IDO-1 in MoDC while such treatments had no effect on IFN-γ-induced IDO-1. Furthermore, we showed that the activation of the transcription factor NF-κB by Tat is essential for the production of IDO-1 by human MoDC. Indeed, Tat activated NF-κB pathway in MoDC as demonstrated by the phosphorylation of p65 in Tat-treated MoDC. Further, we demonstrate that the stimulation of IDO-1 by Tat or by IFN-γ was totally or partially inhibited in the presence of NF-κB inhibitor respectively. These results suggest that Tat and IFN-γ act probably by two distinct mechanisms to induce the production of IDO-1. Our results clearly demonstrated that, although TLR4 pathway is necessary for Tat-induced IDO-1 in MoDC, it seems not to be sufficient since stable transfection of a functional TLR4/MD2 pathway in HEK or HeLa cell lines which are endogenously defectives for TLR4, did not restore the capacity of Tat to induce IDO-1 while IFN-γ treatment induces IDO-1 in HeLa cells independently of TLR4 pathway. These results suggest the involvement of additional stimuli in addition to TLR4 pathway which remain to be identified. Altogether our results demonstrated that, in human MoDC, HIV-1 Tat protein induced IDO-1 expression and activity in a NF-κB dependent-manner by recruiting TLR4 pathway.
Evaporation coefficient and condensation coefficient of vapor under high gas pressure conditions
Authors: Ohashi Kotaro , Kobayashi Kazumichi , Fujii Hiroyuki , Watanabe Masao
Published: May 2020

We investigated the evaporation and condensation coefficients of vapor, which represent evaporation and condensation rates of vapor molecules, under high gas pressure (high gas density) conditions in a system of a vapor/gas-liquid equilibrium state. The mixture gas is composed of condensable gas (vapor) and non-condensable gas (NC gas) molecules. We performed numerical simulations of vapor/gas–liquid equilibrium systems with the Enskog–Vlasov direct simulation Monte Carlo (EVDSMC) method. As a result of the simulations, we found that the evaporation and condensation fluxes decrease with increasing NC gas pressure, which leads to a decrease in the evaporation and condensation coefficients of vapor molecules. Especially, under extremely high gas pressure conditions, the values of these coefficients are close to zero, which means the vapor molecules cannot evaporate and condensate at the interface. Moreover, we found that the vapor molecules behave as NC gas molecules under high gas pressure conditions. We also discussed the reason why NC gas molecules interfere with evaporation and condensation of vapor molecules at the vapor/gas–liquid interface.
Estimation of dietary 14C dose coefficient using 13C-labelled compound administration analysis
Authors: Masuda Tsuyoshi , Yoshioka Toshitada , Takahashi Tomoyuki , Takeda Hiroshi , Hatta Hideo , Matsushita Kensaku , Tako Yasuhiro , Takaku Yuichi , Hisamatsu Shun’ichi
Published: May 2020

Carbon-14 released from nuclear facilities has been assessed to contribute significantly to the radiation dose that people are exposed to through the food chain. However, the current dose coefficient for members of public, which is the ratio of the 50-year committed effective dose to ingested 1 Bq 14C, recommended by the International Commission on Radiological Protection (ICRP) is not based on experimental human metabolic data for 14C in nutrients and diet. Therefore, to validate the coefficient, we administered 13C-labelled nutrients consisting of four amino acids, three fatty acids, and one monosaccharide to volunteers as substitutes for 14C labelled nutrients and measured the 13C concentration in various excreta samples. Although metabolic models were constructed from the excretion data, a significant fraction of administered 13C was not recovered from some nutrients. The dose coefficients of 14C in uniformly labelled Japanese diet, which were estimated under several assumptions about the unrecoverable fraction, varied from (6.2 ± 0.9) × 10–11 to (8.9 ± 4.4) × 10–10 Sv Bq−1 and were approximately comparable to the current value of 5.8 × 10–10 Sv Bq−1 recommended by the ICRP. Further studies are necessary to elucidate the metabolism of 14C in various nutrients in the unrecoverable fraction.
Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential?
Authors: Venn-Watson Stephanie , Lumpkin Richard , Dennis Edward A.
Published: May 2020

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants. Higher circulating concentrations of OCFAs, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are associated with lower risks of cardiometabolic diseases, and higher dietary intake of OCFAs is associated with lower mortality. Population-wide circulating OCFA levels, however, have been declining over recent years. Here, we show C15:0 as an active dietary fatty acid that attenuates inflammation, anemia, dyslipidemia, and fibrosisin vivo, potentially by binding to key metabolic regulators and repairing mitochondrial function. This is the first demonstration of C15:0’s direct role in attenuating multiple comorbidities using relevant physiological mechanisms at established circulating concentrations. Pairing our findings with evidence that (1) C15:0 is not readily made endogenously, (2) lower C15:0 dietary intake and blood concentrations are associated with higher mortality and a poorer physiological state, and (3) C15:0 has demonstrated activities and efficacy that parallel associated health benefits in humans, we propose C15:0 as a potential essential fatty acid. Further studies are needed to evaluate the potential impact of decades of reduced intake of OCFA-containing foods as contributors to C15:0 deficiencies and susceptibilities to chronic disease.
Hybrid optical fiber for light-induced superconductivity
Authors: Sedov Evgeny , Sedova Irina , Arakelian Sergey , Eramo Giuseppe , Kavokin Alexey
Published: May 2020

We exploit the recent proposals for the light-induced superconductivity mediated by a Bose-Einstein condensate of exciton-polaritons to design a superconducting fiber that would enable long-distance transport of a supercurrent at elevated temperatures. The proposed fiber consists of a conventional core made of a silica glass with the first cladding layer formed by a material sustaining dipole-polarised excitons with a binding energy exceeding 25 meV. To be specific, we consider a perovskite cladding layer of 20 nm width. The second cladding layer is made of a conventional superconductor such as aluminium. The fiber is covered by a conventional coating buffer and by a plastic outer jacket. We argue that the critical temperature for a superconducting phase transition in the second cladding layer may be strongly enhanced due to the coupling of the superconductor to a bosonic condensate of exciton-polaritons optically induced by the evanescent part of the guiding mode confined in the core. The guided light mode would penetrate to the first cladding layer and provide the strong exciton-photon coupling regime. We run simulations that confirm the validity of the proposed concept. The fabrication of superconducting fibers where a high-temperature superconductivity could be controlled by light would enable passing superconducting currents over extremely long distances.
Non-invasive tunnelled catheter reposition (NTCR): A simple and safe method to restore central tunnelled catheter function for haemodialysis
Authors: Porazko Tomasz , Hobot Jacek , Klinger Marian
Published: May 2020

Despite all efforts, still many end-stage kidney disease (ESKD) patients are dialysed using a central tunnelled catheter (CTC) as vascular access. When the CTC blood flow becomes ineffective, a number of protocols are advised. However, all of them are time- and cost-consuming. The manoeuvre of a non-invasive tunnelled catheter reposition (NTCR) was introduced to restore the CTC function. NTCR was based on gentle movements of the CTC, with or without a simultaneous flushing of the CTC lines, which resulted in a quick reposition of the CTC tip. This study comprises the analysis of a total of 297 NTCRs, which were performed in 114 patients, thus enabling an effective blood flow after 133 procedures (44.7%).Partially effective blood flow followed 123 procedures (41.4%), and it failed altogether in 41 cases (13.9%). Overall, 86% of conducted NTCRs improved the CTC patency to perform a haemodialysis session. The procedure could be successfully repeated, with a similar result after the first and the second attempt. Complications were observed only after 3.4% of all interventions. The novel NTCR manoeuvre was safe and effective in the majority of the CTC dysfunction episodes. It seemed to reduce fibrinolytic usage, allowed an immediate haemodialysis session commencement, therefore, it might save both the costs and the nursing staff time.
Enzyme- and gene-specific biases in reverse transcription of RNA raise concerns for evaluating gene expression
Authors: Minshall Nicola , Git Anna
Published: May 2020

Reverse transcription is the first step of most analyses of gene expression, yet the quantitative biases it introduces are largely overlooked. Following a series of purpose-designed systematic experiments we cherry-pick examples of various biases introduced by reverse transcription, and alert the “gene expression community” to the pitfalls and improved practice of this fundamental technique.
The IL-33-induced p38-/JNK1/2-TNFα axis is antagonized by activation of β-adrenergic-receptors in dendritic cells
Authors: Helbig Christiane , Weber Franziska , Andreas Nico , Herdegen Thomas , Gaestel Matthias , Kamradt Thomas , Drube Sebastian
Published: May 2020

IL-33, an IL-1 cytokine superfamily member, induces the activation of the canonical NF-κB signaling, and of Mitogen Activated Protein Kinases (MAPKs). In dendritic cells (DCs) IL-33 induces the production of IL-6, IL-13 and TNFα. Thereby, the production of IL-6 depends on RelA whereas the production of IL-13 depends on the p38-MK2/3 signaling module. Here, we show that in addition to p65 and the p38-MK2/3 signaling module, JNK1/2 are essential for the IL-33-induced TNFα production. The central roles of JNK1/2 and p38 in DCs are underpinned by the fact that these two MAPK pathways are controlled by activated β-adrenergic receptors resulting in a selective regulation of the IL-33-induced TNFα response in DCs.
Cyclin D2-knock-out mice with attenuated dentate gyrus neurogenesis have robust deficits in long-term memory formation
Authors: Petkova Stela P. , Pride Michael , Klocke Carolyn , Fenton Timothy A. , White Jeannine , Lein Pamela J. , Ellegood Jacob , Lerch Jason P. , Silverman Jill L. , Waldau Ben
Published: May 2020

Neurobehavioral studies have produced contradictory findings concerning the function of neurogenesis in the adult dentate gyrus. Previous studies have proved inconsistent across several behavioral endpoints thought to be dependent on dentate neurogenesis, including memory acquisition, short-term and long-term retention of memory, pattern separation, and reversal learning. We hypothesized that the main function of dentate neurogenesis is long-term memory formation because we assumed that a newly formed and integrated neuron would have a long-term impact on the local neural network. We used a cyclin D2-knock-out (cyclin D2−/−) mouse model of endogenously deficient dentate neurogenesis to test this hypothesis. We found that cyclin D2−/− mice had robust and sustained loss of long-term memory in two separate behavioral tasks, Morris water maze (MWM) and touchscreen intermediate pattern separation. Moreover, after adjusting for differences in brain volumes determined by magnetic resonance (MR) imaging, reduced dentate neurogenesis moderately correlated with deficits in memory retention after 24 hours. Importantly, cyclin D2−/− mice did not show deficits in learning acquisition in a touchscreen paradigm of intermediate pattern separation or MWM platform location, indicating intact short-term memory. Further evaluation of cyclin D2−/− mice is necessary to confirm that deficits are specifically linked to dentate gyrus neurogenesis since cyclin D2−/− mice also have a reduced size of the olfactory bulb, hippocampus, cerebellum and cortex besides reduced dentate gyrus neurogenesis.
Serum level of HDL particles are independently associated with long-term prognosis in patients with coronary artery disease: The GENES study
Authors: Duparc Thibaut , Ruidavets Jean-Bernard , Genoux Annelise , Ingueneau Cécile , Najib Souad , Ferrières Jean , Perret Bertrand , Martinez Laurent O.
Published: May 2020

HDL-Cholesterol (HDL-C) is not an accurate surrogate marker to measure the cardioprotective functions of HDL in coronary artery diseases (CAD) patients. Hence, measurement of other HDL-related parameters may have prognostic superiority over HDL-C. In this work, we examined the predictive value of HDL particles profile for long-term mortality in CAD patients and to compare its informative value to that of HDL-C and apoA-I. HDL particles profiles were measured by nuclear magnetic resonance (NMR) spectroscopy in 214 male participants with stable CAD (45–74 years). Median follow up was 12.5 years with a 36.4% mortality rate. Cardiovascular mortality accounted for 64.5%. Mean concentrations of total HDL particles (HDL-P), small-sized HDL (SHDL-P) and apoA-I were lower in deceased than in surviving patients whereas no difference was observed according to HDL-C and large HDL particles. All NMR-HDL measures were correlated between themselves and with other HDL markers (HDL-C, apoA-I and LpA-I). In a multivariate model adjusted for cardiovascular risk factors and bioclinical variables, HDL-P and SHDL-P displayed the strongest inverse association with all-cause and cardiovascular mortality. Weaker associations were recorded for apoA-I. Based on our results, we conclude that HDL particle profile measured by NMR spectroscopy should be considered to better stratify risk in population at high risk or in the setting of pharmacotherapy.