bluuebunny/crossref_metadata_2025 huggingface dataset:
Washington State Disaster Risk and Preparedness: A Primer for Health Care Providers
Authors: Morris Stephen C.
Published: April 2020

Disaster in Washington State (USA) is inevitable. It is incumbent on health care providers to understand the practice environment as it will be affected by disasters. This means understanding the basic concepts of emergency management, local to national emergency response structure, and the risks and vulnerabilities of the region where one works. This understanding will help health care providers anticipate and prepare for disaster response and recovery. Washington State has many unique features with regard to climate and geography, population, public health, and general infrastructure that create significant vulnerabilities to disaster and strengths with regard to potential response and recovery. This report attempts to define and contextualize emergency management and to condense the extensive research and planning that has been conducted in Washington State surrounding disaster assessment, planning, mitigation, and response from a health care providerʼs prospective. The aim is to increase awareness of and preparation for disaster-related topics among health care providers by creating informed responders.
Automatic Fiber Length Measurements with a Multi-Stencil Fast Marching Method on Microscopy Images
Authors: Liu Chanjuan , Bergmeijer Menno , Pierrat Sébastien , Guise Olivier
Published: April 2020

Fiber length has a strong impact on the mechanical properties of composite materials. It is one of the most important quantitative features in characterizing microstructures for understanding the material performance. Studies conducted to determine fiber length distribution have primarily focused on sample preparation and fiber dispersion. However, the subsequent image analysis is frequently performed manually or semi-automatically, which either requires careful sample preparation or manual intervention in the image analysis and processing. In this article, an image processing and analysis method has been developed based on medial axis transformation via the multi-stencil fast marching method for fiber length measurements on acquired microscopy images. The developed method can be implemented fully automatically and without any user induced delays. This method offers high efficiency, sub-pixel accuracy, and excellent statistical representativity.
Unterrichtsstörungen – eine Frage der Lehre!?
Authors: Schlosser Daniela , Rebmann Marius
Published: April 2020

Zusammenfassung. Unterrichtsstörungen werden meist oder fast ausschließlich den Lernenden zugeschrieben. Dass auch Lehrende die Ursache von Unterrichtsstörungen sein können und wie sie erkannt bzw. vermieden werden können, wird im nachfolgenden Beitrag geschildert.
Reforestation as a Local Cooling Mechanism
Authors: Sidder Aaron
Published: April 2020

Reforestation has been shown to cool surface temperatures, and a novel study suggests it may also reduce air temperature up to several stories above the ground.
Chinese Swamp Core Reveals 47,000 Years of Monsoon History
Authors: Stanley Sarah
Published: April 2020

Magnetic analysis of mineral composition supports the importance of tropical climate processes in shaping long-term monsoon patterns.
Cross organelle stress response disruption promotes gentamicin-induced proteotoxicity
Authors: Igwebuike Chinaemere , Yaglom Julia , Huiting Leah , Feng Hui , Campbell Joshua D. , Wang Zhiyong , Havasi Andrea , Pimentel David , Sherman Michael Y. , Borkan Steven C.
Published: April 2020

Gentamicin is a nephrotoxic antibiotic that causes acute kidney injury (AKI) primarily by targeting the proximal tubule epithelial cell. The development of an effective therapy for gentamicin-induced renal cell injury is limited by incomplete mechanistic insight. To address this challenge, we propose that RNAi signal pathway screening could identify a unifying mechanism of gentamicin-induced cell injury and suggest a therapeutic strategy to ameliorate it. Computational analysis of RNAi signal screens in gentamicin-exposed human proximal tubule cells suggested the cross-organelle stress response (CORE), the unfolded protein response (UPR), and cell chaperones as key targets of gentamicin-induced injury. To test this hypothesis, we assessed the effect of gentamicin on the CORE, UPR, and cell chaperone function, and tested the therapeutic efficacy of enhancing cell chaperone content. Early gentamicin exposure disrupted the CORE, evidenced by a rise in the ATP:ADP ratio, mitochondrial-specific H2O2 accumulation, Drp-1-mediated mitochondrial fragmentation, and endoplasmic reticulum–mitochondrial dissociation. CORE disruption preceded measurable increases in whole-cell oxidative stress, misfolded protein content, transcriptional UPR activation, and its untoward downstream effects: CHOP expression, PARP cleavage, and cell death. Geranylgeranylacetone, a therapeutic that increases cell chaperone content, prevented mitochondrial H2O2 accumulation, preserved the CORE, reduced the burden of misfolded proteins and CHOP expression, and significantly improved survival in gentamicin-exposed cells. We identify CORE disruption as an early and remediable cause of gentamicin proteotoxicity that precedes downstream UPR activation and cell death. Preserving the CORE significantly improves renal cell survival likely by reducing organelle-specific proteotoxicity during gentamicin exposure.
Rapid time-resolved Circular Polarization Luminescence (CPL) emission spectroscopy
Authors: MacKenzie Lewis E. , Pålsson Lars-Olof , Parker David , Beeby Andrew , Pal Robert
Published: April 2020

Circular polarisation luminescence (CPL) emission spectroscopy is a powerful tool for probing the fundamental chiroptical features of optically emissive chiral molecular systems. However, uptake of CPL spectroscopy has been impeded by the limitations of conventional scanning monochromator (SM) CPL spectrometers, which are costly to acquire and maintain, and typically require tens of minutes to acquire a typical CPL spectrum. Here, we demonstrate a design of CPL spectrometer which uses rapid readout solid state (SS) spectrometer detectors and a dual channel optical layout to acquire CPL spectra in as little as 10 milliseconds. We validate and demonstrate equivalent CPL measurement by measuring CPL spectra of two reference europium(III) complexes. Further, we demonstrate time-gated CPL acquisition, enabling long-lived CPL luminescence to be distinguished from short-lived emission of other fluorescent species. We anticipate that SS-CPL spectrometers will enable flexible, rapid, and relatively low-cost CPL spectroscopy for diverse applications.
Intercellular communication between artificial cells by allosteric amplification of a molecular signal
Authors: Buddingh’ Bastiaan C. , Elzinga Janneke , van Hest Jan C. M.
Published: April 2020

Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.
METTL3 is essential for postnatal development of brown adipose tissue and energy expenditure in mice
Authors: Wang Yuqin , Gao Ming , Zhu Fuxing , Li Xinzhi , Yang Ying , Yan Qiuxin , Jia Linna , Xie Liwei , Chen Zheng
Published: April 2020

Brown adipose tissue (BAT) undergoes rapid postnatal development and then protects against cold and obesity into adulthood. However, the molecular mechanism that determines postnatal development and maturation of BAT is largely unknown. Here we show that METTL3 (a key RNA methyltransferase) expression increases significantly in interscapular brown adipose tissue (iBAT) after birth and plays an essential role in the postnatal development and maturation of iBAT. BAT-specific deletion of Mettl3 severely impairs maturation of BAT in vivo by decreasing m6A modification and expression of Prdm16, Pparg, and Ucp1 transcripts, which leads to a marked reduction in BAT-mediated adaptive thermogenesis and promotes high-fat diet (HFD)-induced obesity and systemic insulin resistance. These data demonstrate that METTL3 is an essential regulator that controls iBAT postnatal development and energy homeostasis.
Oncogenic KrasG12D causes myeloproliferation via NLRP3 inflammasome activation
Authors: Hamarsheh Shaima’a , Osswald Lena , Saller Benedikt S. , Unger Susanne , De Feo Donatella , Vinnakota Janaki Manoja , Konantz Martina , Uhl Franziska M. , Becker Heiko , Lübbert Michael , Shoumariyeh Khalid , Schürch Christoph , Andrieux Geoffroy , Venhoff Nils , Schmitt-Graeff Annette , Duquesne Sandra , Pfeifer Dietmar , Cooper Matthew A. , Lengerke Claudia , Boerries Melanie , Duyster Justus , Niemeyer Charlotte M. , Erlacher Miriam , Blazar Bruce R. , Becher Burkard , Groß Olaf , Brummer Tilman , Zeiser Robert
Published: April 2020

Oncogenic Ras mutations occur in various leukemias. It was unclear if, besides the direct transforming effect via constant RAS/MEK/ERK signaling, an inflammation-related effect of KRAS contributes to the disease. Here, we identify a functional link between oncogenic KrasG12D and NLRP3 inflammasome activation in murine and human cells. Mice expressing active KrasG12D in the hematopoietic system developed myeloproliferation and cytopenia, which is reversed in KrasG12D mice lacking NLRP3 in the hematopoietic system. Therapeutic IL-1-receptor blockade or NLRP3-inhibition reduces myeloproliferation and improves hematopoiesis. Mechanistically, KrasG12D-RAC1 activation induces reactive oxygen species (ROS) production causing NLRP3 inflammasome-activation. In agreement with our observations in mice, patient-derived myeloid leukemia cells exhibit KRAS/RAC1/ROS/NLRP3/IL-1β axis activity. Our findings indicate that oncogenic KRAS not only act via its canonical oncogenic driver function, but also enhances the activation of the pro-inflammatory RAC1/ROS/NLRP3/IL-1β axis. This paves the way for a therapeutic approach based on immune modulation via NLRP3 blockade in KRAS-mutant myeloid malignancies.
Comprehensive scan for nonmagnetic Weyl semimetals with nonlinear optical response
Authors: Xu Qiunan , Zhang Yang , Koepernik Klaus , Shi Wujun , van den Brink Jeroen , Felser Claudia , Sun Yan
Published: April 2020

First-principles calculations have recently been used to develop comprehensive databases of nonmagnetic topological materials that are protected by time-reversal or crystalline symmetry. However, owing to the low symmetry requirement of Weyl points, a symmetry-based approach to identifying topological states cannot be applied to Weyl semimetals (WSMs). To date, WSMs with Weyl points in arbitrary positions are absent from the well-known databases. In this work, we develop an efficient algorithm to search for Weyl points automatically and establish a database of nonmagnetic WSMs with Weyl points near the Fermi level based on the experimental non-centrosymmetric crystal structures in the Inorganic Crystal Structure Database (ICSD). In total, 46 Weyl semimetals were discovered to have nearly clean Fermi surfaces and Weyl points within 300 meV of the Fermi level. Nine of them are chiral structures which may exhibit the quantized circular photogalvanic effect. In addition, the nonlinear optical response is studied and the giant shift current is explored. Besides nonmagnetic WSMs, our powerful tools can also be used in the discovery of magnetic topological materials.
Near-field corrosion interactions between glass and corrosion resistant alloys
Authors: Guo Xiaolei , Gin Stephane , Liu Hongshen , Ngo Dien , Luo Jiawei , Kim Seong H. , Mohanty Chandi , Vienna John D. , Ryan Joseph V. , Frankel Gerald S.
Published: April 2020

This study explores the corrosion interactions between model nuclear waste glass materials and corrosion resistant alloys, under accelerated conditions that simulate the near field of a nuclear waste repository. The interactions between the corrosion of stainless steel (SS) 316, alloy G30, or alloy 625, and international simple glass or soda-lime silica glass are systematically studied. The dissimilar materials were exposed in close proximity to each other in different electrolytes at 90 °C. After exposure, the glass surface exposed near metals showed different regimes of corrosion, with distinct surface morphologies and chemistries that were likely affected by the local environment created by the localized corrosion of metals. Surface and solution analyses showed that the corrosion rate of glass was enhanced by the presence of metals. Infrared spectroscopy data suggested the local build-up of stresses in the contact area of glass, which may lead to the mechanical instability of the glass alteration layer. On the other hand, the effect of glass on metal corrosion is strongly dependent on the leaching solution. In electrolytes containing abundant aggressive anions such as Cl−, glass seems to suppress the localized corrosion of SS by the precipitation of a Si-rich surface film that protects the SS substrate from solutions. However, in less aggressive electrolytes, the corrosion rate of SS was increased by the presence of glass corrosion products. Overall, our study showed that the hidden and localized damage on glass in contact with metals may enhance the release rate of glass components compared to typical uniform glass corrosion.
On-demand generation and characterization of a microwave time-bin qubit
Authors: Ilves J. , Kono S. , Sunada Y. , Yamazaki S. , Kim M. , Koshino K. , Nakamura Y.
Published: April 2020

Superconducting circuits offer a scalable platform for the construction of large-scale quantum networks, where information can be encoded in multiple temporal modes of propagating microwaves. Characterization of such microwave signals with a method extendable to an arbitrary number of temporal modes with a single detector and demonstration of their phase-robust nature are of great interest. Here, we show the on-demand generation and Wigner tomography of a microwave time-bin qubit with superconducting circuit quantum electrodynamics architecture. We perform the tomography with a single heterodyne detector by dynamically switching the measurement quadrature independently for two temporal modes through the pump phase of a phase-sensitive amplifier. We demonstrate that the time-bin encoding scheme relies on the relative phase between the two modes and does not need a shared phase reference between sender and receiver.
Overdispersed gene expression in schizophrenia
Authors: Huang Guangzao , Osorio Daniel , Guan Jinting , Ji Guoli , Cai James J.
Published: April 2020

Schizophrenia (SCZ) is a severe, highly heterogeneous psychiatric disorder with varied clinical presentations. The polygenic genetic architecture of SCZ makes identification of causal variants a daunting task. Gene expression analyses hold the promise of revealing connections between dysregulated transcription and underlying variants in SCZ. However, the most commonly used differential expression analysis often assumes grouped samples are from homogeneous populations and thus cannot be used to detect expression variance differences between samples. Here, we applied the test for equality of variances to normalized expression data, generated by the CommonMind Consortium (CMC), from brains of 212 SCZ and 214 unaffected control (CTL) samples. We identified 87 genes, includingVEGFA(vascular endothelial growth factor) andBDNF(brain-derived neurotrophic factor), that showed a significantly higher expression variance among SCZ samples than CTL samples. In contrast, only one gene showed the opposite pattern. To extend our analysis to gene sets, we proposed a Mahalanobis distance-based test for multivariate homogeneity of group dispersions, with which we identified 110 gene sets with a significantly higher expression variability in SCZ, including sets of genes encoding phosphatidylinositol 3-kinase (PI3K) complex and several others involved in cerebellar cortex morphogenesis, neuromuscular junction development, and cerebellar Purkinje cell layer development. Taken together, our results suggest that SCZ brains are characterized by overdispersed gene expression—overall gene expression variability among SCZ samples is significantly higher than that among CTL samples. Our study showcases the application of variability-centric analyses in SCZ research.
A 3 km spatially and temporally consistent European daily soil moisture reanalysis from 2000 to 2015
Authors: Naz Bibi S. , Kollet Stefan , Franssen Harrie-Jan Hendricks , Montzka Carsten , Kurtz Wolfgang
Published: April 2020

High-resolution soil moisture (SM) information is essential to many regional applications in hydrological and climate sciences. Many global estimates of surface SM are provided by satellite sensors, but at coarse spatial resolutions (lower than 25 km), which are not suitable for regional hydrologic and agriculture applications. Here we present a 16 years (2000–2015) high-resolution spatially and temporally consistent surface soil moisture reanalysis (ESSMRA) dataset (3 km, daily) over Europe from a land surface data assimilation system. Coarse-resolution satellite derived soil moisture data were assimilated into the community land model (CLM3.5) using an ensemble Kalman filter scheme, producing a 3 km daily soil moisture reanalysis dataset. Validation against 112 in-situ soil moisture observations over Europe shows that ESSMRA captures the daily, inter-annual, intra-seasonal patterns well with RMSE varying from 0.04 to 0.06 m3m−3 and correlation values above 0.5 over 70% of stations. The dataset presented here provides long-term daily surface soil moisture at a high spatiotemporal resolution and will be beneficial for many hydrological applications over regional and continental scales.
The impacts of intrauterine Bisphenol A exposure on pregnancy and expression of miRNAs related to heart development and diseases in animal model
Authors: Rasdi Zatilfarihiah , Kamaludin Roziana , Ab. Rahim Sharaniza , Syed Ahmad Fuad Syed Baharom , Othman Mohd Hafiz Dzarfan , Siran Rosfaiizah , Mohd Nor Noor Shafina , Abdul Hamid Hasani Narimah , Sheikh Abdul Kadir Siti Hamimah
Published: April 2020

This study aimed to examine the impact of BPA exposure on pregnancy and foetuses on cardiac tissues and the expression of cardiac microRNAs (miRNAs) related to heart development and diseases. Pregnancy is known to be the “critical windows” in determining the offspring physical and cells development in their life after birth. The increment of the risk of cardiovascular disease (CVD) in a later stage of life has been reported by few studies demonstrated from prenatal exposure of BPA. BPA has been shown to alter miRNAs expression profiles for organ development, regeneration and metabolic functions. These alterations have been associated with the risk of CVDs. However, the associations between pregnancy outcomes and miRNAs expression in cardiac of mother- and foetuses-exposed to BPA are still not entirely explored. In BPA-exposed pregnant rat groups, a significant weight gained was observed in comparison to control (p < 0.05). Interestingly, significant changes in systolic and diastolic blood pressure between the first and third trimester of BPA-exposed pregnant rats were also observed (p < 0.05). In BPA-exposed pregnant rats, miR-499-5p was significantly altered in the heart (p < 0.01). Meanwhile, altered miR-17-5p, -208-3p, and -210-3p expressions were observed in all heart of the foetuses from BPA-exposed pregnant rats (p < 0.05). In H&E staining, BPA-exposed foetal hearts showed a sign of fibrosis while BPA-exposed pregnant rats showed muscle remnant. Masson trichrome staining further confirmed the presence of fibrosis observed in BPA-exposed foetal heart and reduced expression of cardiac troponin I (cTnI) was also observed in BPA-exposed foetal heart. In summary, altered cardiac miRNAs with histological changes were observed in both mother- and foetus-exposed BPA These findings put forward the importance of future work to further understand how prenatal BPA exposure affect foetuses in their later stage of life.
Comparison of wavelet and correlation indices of cerebral autoregulation in a pediatric swine model of cardiac arrest
Authors: Liu Xiuyun , Hu Xiao , Brady Ken M. , Koehler Raymond , Smielewski Peter , Czosnyka Marek , Donnelly Joseph , Lee Jennifer K.
Published: April 2020

Existing cerebrovascular blood pressure autoregulation metrics have not been translated to clinical care for pediatric cardiac arrest, in part because signal noise causes high index time-variability. We tested whether a wavelet method that uses near-infrared spectroscopy (NIRS) or intracranial pressure (ICP) decreases index variability compared to that of commonly used correlation indices. We also compared whether the methods identify the optimal arterial blood pressure (ABPopt) and lower limit of autoregulation (LLA). 68 piglets were randomized to cardiac arrest or sham procedure with continuous monitoring of cerebral blood flow using laser Doppler, NIRS and ICP. The arterial blood pressure (ABP) was gradually reduced until it dropped to below the LLA. Several autoregulation indices were calculated using correlation and wavelet methods, including the pressure reactivity index (PRx and wPRx), cerebral oximetry index (COx and wCOx), and hemoglobin volume index (HVx and wHVx). Wavelet methodology had less index variability with smaller standard deviations. Both wavelet and correlation methods distinguished functional autoregulation (ABP above LLA) from dysfunctional autoregulation (ABP below the LLA). Both wavelet and correlation methods also identified ABPopt with high agreement. Thus, wavelet methodology using NIRS may offer an accurate vasoreactivity monitoring method with reduced signal noise after pediatric cardiac arrest.
The conifer root rot pathogens Heterobasidion irregulare and Heterobasidion occidentale employ different strategies to infect Norway spruce
Authors: Hu Yang , Elfstrand Malin , Stenlid Jan , Durling Mikael Brandström , Olson Åke
Published: April 2020

Heterobasidion irregulare and H. occidentale are two closely related conifer root rot pathogens in the H. annosum sensu lato (s.l.) species complex. The two species H. irregulare and H. occidentale have different host preference with pine and non-pine tree species favored, respectively. The comparison of transcriptomes of H. irregulare and H. occidentale growing in Norway spruce bark, a susceptible host non-native to North America, showed large differences in gene expression. Heterobasidion irregulare induced more genes involved in detoxification of host compounds and in production of secondary metabolites, while the transcriptome induced in H. occidentale was more oriented towards carbohydrate degradation. Along with their separated evolutionary history, the difference might be driven by their host preferences as indicated by the differentially expressed genes enriched in particular Gene Ontology terms.
µgreen-db: a reference database for the 23S rRNA gene of eukaryotic plastids and cyanobacteria
Authors: Djemiel Christophe , Plassard Damien , Terrat Sébastien , Crouzet Olivier , Sauze Joana , Mondy Samuel , Nowak Virginie , Wingate Lisa , Ogée Jérôme , Maron Pierre-Alain
Published: April 2020

Studying the ecology of photosynthetic microeukaryotes and prokaryotic cyanobacterial communities requires molecular tools to complement morphological observations. These tools rely on specific genetic markers and require the development of specialised databases to achieve taxonomic assignment. We set up a reference database, called µgreen-db, for the 23S rRNA gene. The sequences were retrieved from generalist (NCBI, SILVA) or Comparative RNA Web (CRW) databases, in addition to a more original approach involving recursive BLAST searches to obtain the best possible sequence recovery. At present, µgreen-db includes 2,326 23S rRNA sequences belonging to both eukaryotes and prokaryotes encompassing 442 unique genera and 736 species of photosynthetic microeukaryotes, cyanobacteria and non-vascular land plants based on the NCBI and AlgaeBase taxonomy. When PR2/SILVA taxonomy is used instead, µgreen-db contains 2,217 sequences (399 unique genera and 696 unique species). Using µgreen-db, we were able to assign 96% of the sequences of the V domain of the 23S rRNA gene obtained by metabarcoding after amplification from soil DNA at the genus level, highlighting good coverage of the database. µgreen-db is accessible at http://microgreen-23sdatabase.ea.inra.fr.
Dynamical Quantum Filtering via Enhanced Scattering of para-H2 on the Orientationally Anisotropic Potential of SrTiO3(001)
Authors: Shimizu Koji , Diño Wilson Agerico , Nakanishi Hiroshi , Kasai Hideaki , Takeyasu Kotaro , Fukutani Katsuyuki , Yajima Ayako
Published: April 2020

Quantum dynamics calculation, performed on top of density functional theory (DFT)-based total energy calculations, show dynamical quantum filtering via enhanced scattering of para-H2 on SrTiO3(001). We attribute this to the strongly orientation-dependent (electrostatic) interaction potential between the H2 (induced) quadrupole moment and the surface electric field gradient of ionic SrTiO3(001). These results suggest that ionic surfaces could function as a scattering/filtering media to realize rotationally state-resolved H2. This could find significant applications not only in H2 storage and transport, but also in realizing materials with pre-determined characteristic properties.
Phenotypic and functional characterization of natural killer cells in rheumatoid arthritis-regulation with interleukin-15
Authors: Lin Syh-Jae , Hsu Chien-Ya , Kuo Ming-Ling , Lee Pei-Tzu , Hsiao Hsiu-Shan , Chen Ji-Yih
Published: April 2020

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction. Previous studies have shown that natural killer (NK) cells may play an important role in the pathogenesis of RA. Interleukin (IL)-15, a pro-inflammatory cytokine which induces proliferation and differentiation of NK cells, is overexpressed in RA. In this present study, we examine various NKRs and adhesion molecule expression on NK cells from RA patients and their response to IL-15 stimulation. We also sought to study cytokine-induced memory-like (CIML) NK cells in RA patients. We established that 1. RA patients had higher NK cell percentages in peripheral blood and their serum IL-15 levels were higher compared to healthy volunteers; 2. NK cells from RA patients showed lower NKp46 expression and an impaired CD69 response to IL-15; 3. NK cells from RA patients showed higher CD158b and CD158e expression but lower CD62L expression; 4. exogenous IL-15 up-regulated CD69, CD158b, CD158e but down-regulated NKp46 and CD62L expression in RA; 5. As to CIML NK cells, restimulation - induced NK cytotoxicity and IFN-γ production was impaired in RA patients, 6. Reduced NKp46, perforin, and granzyme B expression on NK cells was found in RA patients with bone deformity and erosion, 7. RA disease activity (DAS28) showed inverse correlation with the percentages of CD56+CD3− NK cells, and NKp46 and perforin expression on NK cells, respectively. Taken together, our study demonstrated differential expression of various NK receptors in RA patients. NKp46, CD158e, and perforin expression on NK cells may serve as markers of RA severity.
High density cultivation for efficient sesquiterpenoid biosynthesis in Synechocystis sp. PCC 6803
Authors: Dienst Dennis , Wichmann Julian , Mantovani Oliver , Rodrigues João S. , Lindberg Pia
Published: April 2020

Cyanobacteria and microalgae are attractive photoautotrophic host systems for climate-friendly production of fuels and other value-added biochemicals. However, for economic applications further development and implementation of efficient and sustainable cultivation strategies are essential. Here, we present a comparative study on cyanobacterial sesquiterpenoid biosynthesis in Synechocystis sp. PCC 6803 using a commercial lab-scale High Density Cultivation (HDC) platform in the presence of dodecane as in-situ extractant. Operating in a two-step semi-batch mode over a period of eight days, volumetric yields of (E)-α-bisabolene were more than two orders of magnitude higher than previously reported for cyanobacteria, with final titers of 179.4 ± 20.7 mg * L−1. Likewise, yields of the sesquiterpene alcohols (−)-patchoulol and (−)-α-bisabolol were many times higher than under reference conditions, with final titers of 17.3 ± 1.85 mg * L−1 and 96.3 ± 2.2 mg * L−1, respectively. While specific productivity was compromised particularly for (E)-α-bisabolene in the HDC system during phases of high biomass accumulation rates, volumetric productivity enhancements during linear growth at high densities were more pronounced for (E)-α-bisabolene than for the hydroxylated terpenoids. Together, this study provides additional insights into cell density-related process characteristics, introducing HDC as highly efficient strategy for phototrophic terpenoid production in cyanobacteria.
Neuropeptide Y deficiency induces anxiety-like behaviours in zebrafish (Danio rerio)
Authors: Shiozaki Kazuhiro , Kawabe Momoko , Karasuyama Kiwako , Kurachi Takayoshi , Hayashi Akito , Ataka Koji , Iwai Haruki , Takeno Hinako , Hayasaka Oki , Kotani Tomonari , Komatsu Masaharu , Inui Akio
Published: April 2020

Neuropeptide Y (NPY) controls energy homeostasis including orexigenic actions in mammalians and non-mammalians. Recently, NPY has attracted attention as a mediator of emotional behaviour and psychosomatic diseases. However, its functions are not fully understood. We established npy gene-deficient (NPY-KO) zebrafish (Danio rerio) to assess the relationship between NPY and emotional behaviours. The NPY-KO zebrafish exhibited similar growth, but pomc and avp mRNA levels in the brain were higher as compared to wild-type fish. NPY-KO zebrafish exhibited several anxiety-like behaviours, such as a decrease in social interaction in mirror test and decreased locomotion in black-white test. The acute cold stress-treated NPY-KO zebrafish exhibited anxiety-like behaviours such as remaining stationary and swimming along the side of the tank in the mirror test. Moreover, expression levels of anxiety-associated genes (orx and cck) and catecholamine production (gr, mr, th1 and th2) were significantly higher in NPY-KO zebrafish than in wild-type fish. We demonstrated that NPY-KO zebrafish have an anxiety phenotype and a stress-vulnerability like NPY-KO mice, whereby orx and/or catecholamine signalling may be involved in the mechanism actions.
Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a pilot study
Authors: Ragusa Rosetta , Di Molfetta Arianna , D’Aurizio Romina , Del Turco Serena , Cabiati Manuela , Del Ry Silvia , Basta Giuseppina , Pitto Letizia , Amodeo Antonio , Trivella Maria Giovanna , Rizzo Milena , Caselli Chiara
Published: April 2020

Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.
Exploring the configuration spaces of surface materials using time-dependent diffraction patterns and unsupervised learning
Authors: Packwood Daniel M.
Published: April 2020

Computational methods for exploring the atomic configuration spaces of surface materials will lead to breakthroughs in nanotechnology and beyond. In order to develop such methods, especially ones utilizing machine learning approaches, descriptors which encode the structural features of the candidate configurations are required. In this paper, we propose the use of time-dependent electron diffraction simulations to create descriptors for the configurations of surface materials. Our proposal utilizes the fact that the sub-femtosecond time-dependence of electron diffraction patterns are highly sensitive to the arrangement of atoms in the surface region of the material, allowing one to distinguish configurations which possess identical symmetry but differ in the locations of the atoms in the unit cell. We demonstrate the effectiveness of this approach by considering the simple cases of copper(111) and an organic self-assembled monolayer system, and use it to search for metastable configurations of these materials.
Geographic variation in baseline innate immune function does not follow variation in aridity along a tropical environmental gradient
Authors: Nwaogu Chima J. , Cresswell Will , Tieleman B. Irene
Published: April 2020

Geographic variation in aridity determines environmental productivity patterns, including large-scale variability in pathogens, vectors and associated diseases. If disease risk decreases with increasing aridity and is matched by immune defense, we predict a decrease in innate immune function along a gradient of increasing aridity from the cool-wet forest to the hot-dry Sahel, from south to north in Nigeria. We sampled blood and measured five innate immune indices from 286 Common BulbulsPycnonotus barbatusbetween 6 and 13°N. We sampled in the dry season; we resampled the first location (Jos) also as the last sample location to test temporal change in immune function. Immune indices did not decrease with aridity. One immune index, nitric oxide concentration showed a weak quadratic pattern. In Jos, ovotransferrin concentration, haemagglutination and haemolysis titres increased 12 weeks into the dry season, contrary to expectations that immune indices should decrease with increased dryness. In this tropical system, innate immune function does not decrease with increasing aridity but temporal factors within a location may influence immune function more strongly than spatial variation in aridity, suggesting that immune variation does not follow a simple environmental productivity pattern. Consequently, caution should probably be exercised in predicting effects of climate variability on immune function or disease risk.
Assessment of metals induced histopathological and gene expression changes in different organs of non-diabetic and diabetic rats
Authors: Riaz Muhammad Ahsan , Nisa Zaib Un , Anjum Muhammad Sohail , Butt Hira , Mehmood Azra , Riaz Ayesha , Akhtar Amtul Bari Tabinda
Published: April 2020

Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrils and vacuolization in the heart tissue of metal treated groups as evident from hematoxylin and eosin (H & E) staining. The kidney tissue of rats treated with heavy metals showed tubular degeneration, fibrosis, hemorrhage, and vacuolation. The liver of the heavy metals treated rats exhibited cellular degeneration and necrosis. The pancreatic tissue of streptozotocin injected untreated and metal treated rats revealed severe degeneration, necrosis, degranulation, shrinkage, and depression in the islets of Langerhans. Increased red pulp area and congestion were observed in the spleen of the metal mixture treated non-diabetic and diabetic rats. In line with the histological data, the qRT-PCR analysis showed downregulated expression ofBcl2and upregulation ofCaspase-3in non-diabetic and diabetic metal treated rats as compared to the non-diabetic untreated rats. In conclusion, the present study revealed, diabetic rats are more prone to metal alone as well as metal mixture induced organ damage as compared to non-diabetic rats.
Bidirectional Association Between Psoriasis and Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis
Authors: Ger Tzong-Yun , Fu Yun , Chi Ching-Chi
Published: April 2020

The link between psoriasis and obstructive sleep apnea (OSA) has not been confirmed. We aimed to investigate the relationship between psoriasis and OSA. We conducted a systematic review and meta-analysis of case-control, cross-sectional, and cohort studies on the association between psoriasis and OSA. We searched MEDLINE and Embase for relevant studies on May 11, 2019. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included studies. We performed random-effects model meta-analysis to calculate pooled odds ratio (ORs) with 95% confidence intervals (CIs) for case-control and cross-sectional studies as well as pooled incidence rate ratio (IRR) with 95% CIs for cohort studies in association between psoriasis and OSA. A total of 4 case-control or cross-sectional studies and 3 cohort studies with a total of 5,840,495 subjects were included. We identified a significantly increased odds for OSA in psoriasis patients (pooled OR 2.60; 95% CI 1.07–6.32), and significantly increased risk for psoriasis in OSA patients (pooled IRR 2.52; 95% CI 1.89–3.36). In conclusion, our study identified a bidirectional association between psoriasis and OSA. Sleep quality should be inquired in patients with psoriasis. Respirologist consultation or polysomnography may be indicated for those presenting with night snoring, recurrent awaking, and excessive daytime sleepiness.
MicroRNA-331 and microRNA-151-3p as biomarkers in patients with ST-segment elevation myocardial infarction
Authors: Horváth Martin , Horváthová Veronika , Hájek Petr , Štěchovský Cyril , Honěk Jakub , Šenolt Ladislav , Veselka Josef
Published: April 2020

We sought to analyse plasma levels of peripheral blood microRNAs (miRs) as biomarkers of ST-segment-elevation myocardial infarction (STEMI) due to type-1 myocardial infarction as a model situation of vulnerable plaque (VP) rupture. Samples of 20 patients with STEMI were compared both with a group of patients without angina pectoris in whom coronary angiogram did not reveal coronary atherosclerotic disease (no coronary atherosclerosis-NCA) and a group of patients with stable angina pectoris and at least one significant coronary artery stenosis (stable coronary artery disease-SCAD). This study design allowed us to identify miRs deregulated in the setting of acute coronary artery occlusion due to VP rupture. Based on an initial large scale miR assay screening, we selected a total of 12 miRs (three study miRs and nine controls) that were tested in the study. Two of the study miRs (miR-331 and miR-151-3p) significantly distinguished STEMI patients from the control groups, while ROC analysis confirmed their suitability as biomarkers. Importantly, this was observed in patients presenting early with STEMI, even before the markers of myocardial necrosis (cardiac troponin I, miR-208 and miR-499) were elevated, which suggests that the origin of miR-331 and miR-151-3p might be in the VP. In conclusion, the study provides two novel biomarkers observed in STEMI, which may be associated with plaque rupture.
Author Correction: Robust skill of decadal climate predictions
Authors: Smith D. M. , Eade R. , Scaife A. A. , Caron L.-P. , Danabasoglu G. , DelSole T. M. , Delworth T. , Doblas-Reyes F. J. , Dunstone N. J. , Hermanson L. , Kharin V. , Kimoto M. , Merryfield W. J. , Mochizuki T. , Müller W. A. , Pohlmann H. , Yeager S. , Yang X.
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Quantifying the use of connected digital products in clinical research
Authors: Marra Caroline , Chen Jacqueline L. , Coravos Andrea , Stern Ariel D.
Published: April 2020

Over recent years, the adoption of connected technologies has grown dramatically, with potential for improving health care delivery, research, and patient experience. Yet, little has been documented about the prevalence and use of connected digital products (e.g., products that capture physiological and behavioral metrics) in formal clinical research. Using 18 years of data from ClinicalTrials.gov, we document substantial growth in the use of connected digital products in clinical trials (~34% CAGR) and show that these products have been used across all phases of research and by a diverse group of trial sponsors. We identify four distinct use cases for how such connected products have been integrated within clinical trial design and suggest implications for various stakeholders engaging in clinical research.
Transmembrane protein rotaxanes reveal kinetic traps in the refolding of translocated substrates
Authors: Feng Jianfei , Martin-Baniandres Pablo , Booth Michael J. , Veggiani Gianluca , Howarth Mark , Bayley Hagan , Rodriguez-Larrea David
Published: April 2020

Understanding protein folding under conditions similar to those found in vivo remains challenging. Folding occurs mainly vectorially as a polypeptide emerges from the ribosome or from a membrane translocon. Protein folding during membrane translocation is particularly difficult to study. Here, we describe a single-molecule method to characterize the folded state of individual proteins after membrane translocation, by monitoring the ionic current passing through the pore. We tag both N and C termini of a model protein, thioredoxin, with biotinylated oligonucleotides. Under an electric potential, one of the oligonucleotides is pulled through a α-hemolysin nanopore driving the unfolding and translocation of the protein. We trap the protein in the nanopore as a rotaxane-like complex using streptavidin stoppers. The protein is subjected to cycles of unfolding-translocation-refolding switching the voltage polarity. We find that the refolding pathway after translocation is slower than in bulk solution due to the existence of kinetic traps.
Anti-HIV agent azidothymidine decreases Tet(X)-mediated bacterial resistance to tigecycline in Escherichia coli
Authors: Liu Yuan , Jia Yuqian , Yang Kangni , Li Ruichao , Xiao Xia , Wang Zhiqiang
Published: April 2020

Recent emergence of high-level tigecycline resistance mediated by Tet(X3/X4) in Enterobacteriaceae undoubtably constitutes a serious threat for public health worldwide. Antibiotic adjuvant strategy makes antibiotic more effective against these resistant pathogens through interfering intrinsic resistance mechanisms or enhancing antibiotic actions. Herein, we screened a collection of drugs to identify compounds that are able to restore tigecycline activity against resistant pathogens. Encouragingly, we discovered that anti-HIV agent azidothymidine dramatically potentiates tigecycline activity against clinically resistant bacteria. Meanwhile, addition of azidothymidine prevents the evolution of tigecycline resistance inE. coliand the naturally occurring horizontal transfer oftet(X4). Evidence demonstrated that azidothymidine specifically inhibits DNA synthesis and suppresses resistance enzyme activity. Moreover, in in vivo infection models by Tet(X4)-expressionE. coli, the combination of azidothymidine and tigecycline achieved remarkable treatment benefits including increased survival and decreased bacterial burden. These findings provide an effective regimen to treat infections caused by tigecycline-resistantEscherichia coli.
Molecular bases for HOIPINs-mediated inhibition of LUBAC and innate immune responses
Authors: Oikawa Daisuke , Sato Yusuke , Ohtake Fumiaki , Komakura Keidai , Hanada Kazuki , Sugawara Koji , Terawaki Seigo , Mizukami Yukari , Phuong Hoang T. , Iio Kiyosei , Obika Shingo , Fukushi Masaya , Irie Takashi , Tsuruta Daisuke , Sakamoto Shinji , Tanaka Keiji , Saeki Yasushi , Fukai Shuya , Tokunaga Fuminori
Published: April 2020

The NF-κB and interferon antiviral signaling pathways play pivotal roles in inflammatory and innate immune responses. The LUBAC ubiquitin ligase complex, composed of the HOIP, HOIL-1L, and SHARPIN subunits, activates the canonical NF-κB pathway through Met1-linked linear ubiquitination. We identified small-molecule chemical inhibitors of LUBAC, HOIPIN-1 and HOIPIN-8. Here we show that HOIPINs down-regulate not only the proinflammatory cytokine-induced canonical NF-κB pathway, but also various pathogen-associated molecular pattern-induced antiviral pathways. Structural analyses indicated that HOIPINs inhibit the RING-HECT-hybrid reaction in HOIP by modifying the active Cys885, and residues in the C-terminal LDD domain, such as Arg935 and Asp936, facilitate the binding of HOIPINs to LUBAC. HOIPINs effectively induce cell death in activated B cell-like diffuse large B cell lymphoma cells, and alleviate imiquimod-induced psoriasis in model mice. These results reveal the molecular and cellular bases of LUBAC inhibition by HOIPINs, and demonstrate their potential therapeutic uses.
Atomically dispersed palladium catalyses Suzuki–Miyaura reactions under phosphine-free conditions
Authors: Ding Guodong , Hao Leiduan , Xu Haiping , Wang Liguang , Chen Jian , Li Tao , Tu Xinman , Zhang Qiang
Published: April 2020

Single-atom catalysts have emerged as a new frontier in catalysis science. However, their applications are still limited to small molecule activations in the gas phase, the classic organic transformations catalyzed by single-atom catalysts are still rare. Here, we report the use of a single-atom Pd catalyst for the classic Suzuki–Miyaura carbon–carbon coupling reaction under phosphine-free and open-air conditions at room temperature. The single-atom Pd catalyst is prepared through anchoring Pd on bimetal oxides (Pd-ZnO-ZrO2). The significant synergetic effect of ZnO and ZrO2is observed. The catalyst exhibits high activity and tolerance of a wide scope of substrates. Characterization demonstrates that Pd single atoms are coordinated with two oxygen atoms in Pd-ZnO-ZrO2 catalyst. The catalyst can be fabricated on a multi-gram scale using a simple in situ co-precipitation method, which endows this catalytic system with great potential in practical applications.