bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-association and subcellular localization of Puumala hantavirus envelope proteins
Authors: Sperber Hannah Sabeth , Welke Robert-William , Petazzi Roberto Arturo , Bergmann Ronny , Schade Matthias , Shai Yechiel , Chiantia Salvatore , Herrmann Andreas , Schwarzer Roland
Published: January 2019

Hantavirus assembly and budding are governed by the surface glycoproteins Gn and Gc. In this study, we investigated the glycoproteins of Puumala, the most abundant Hantavirus species in Europe, using fluorescently labeled wild-type constructs and cytoplasmic tail (CT) mutants. We analyzed their intracellular distribution, co-localization and oligomerization, applying comprehensive live, single-cell fluorescence techniques, including confocal microscopy, imaging flow cytometry, anisotropy imaging and Number&Brightness analysis. We demonstrate that Gc is significantly enriched in the Golgi apparatus in absence of other viral components, while Gn is mainly restricted to the endoplasmic reticulum (ER). Importantly, upon co-expression both glycoproteins were found in the Golgi apparatus. Furthermore, we show that an intact CT of Gc is necessary for efficient Golgi localization, while the CT of Gn influences protein stability. Finally, we found that Gn assembles into higher-order homo-oligomers, mainly dimers and tetramers, in the ER while Gc was present as mixture of monomers and dimers within the Golgi apparatus. Our findings suggest that PUUV Gc is the driving factor of the targeting of Gc and Gn to the Golgi region, while Gn possesses a significantly stronger self-association potential.
3D vessel-wall virtual histology of whole-body perfused mice using a novel heavy element stain
Authors: Dunmore-Buyze P. Joy , Cruje Charmainne , Nong Zengxuan , Lee Jason J. , Kiernan John A. , Pickering J. Geoffrey , Drangova Maria
Published: January 2019

Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute flushing with detergent-containing saline followed by 15-minute perfusion with the stain and a final 5-minute saline flush), animals are scanned using micro-CT. We demonstrate that the new staining protocol enables sharp delineation of the vessel walls in three dimensions over the whole body; corresponding histological analysis verified that the CT stain is localized primarily in the endothelial cells and media of large arteries and the endothelium of smaller vessels, such as the coronaries. The rapid perfusion and scanning protocol ensured that all tissues are available for further analysis via higher resolution CT of smaller sections or traditional histological sectioning.
The Impact of Cardiac Lipotoxicity on Cardiac Function and Mirnas Signature in Obese and Non-Obese Rats with Myocardial Infarction
Authors: Marín-Royo Gema , Ortega-Hernández Adriana , Martínez-Martínez Ernesto , Jurado-López Raquel , Luaces María , Islas Fabián , Gómez-Garre Dulcenombre , Delgado-Valero Beatriz , Lagunas Esther , Ramchandani Bunty , García-Bouza Mónica , Nieto María Luisa , Cachofeiro Victoria
Published: January 2019

Cardiac lipotoxicity is involved in the cardiac functional consequences associated with obesity. Therefore, the aim of this study was to explore whether changes in the mitochondrial lipid cardiac profile could reflect differences in cardiac function and structure in obese and non-obese rats with myocardial infarction (MI). Whether these changes can also be reflected in a specific plasma miRNA signature as markers of cardiac damage was also evaluated. Rats were fed with either standard (3.5% fat) or high fat diet (35% fat) for 6 weeks before the induction of MI and sacrificed 4 weeks later. MI showed cardiac lipotoxicity independently of the presence of obesity, although obese and non-obese rats did not present the same cardiac lipid profile at mitochondrial level. Several cardiac lipid species in mitochondria, including cardiolipins and triglycerides, were associated with myocardial fibrosis, with mitochondrial triglyceride levels being independently associated with it; this supports that lipotoxicity can affect cardiac function. MI down-regulated plasma levels of miRNA 15b-5p and 194-5p in obese and non-obese animals, which were associated with cardiac function, mitochondrial lipids and myocardial fibrosis, with miRNA 15b-5p levels being independently associated with cardiac fibrosis. This could support that lipotoxicity could affect heart function by modulating plasma miRNAs.
Identification of epileptic brain states by dynamic functional connectivity analysis of simultaneous EEG-fMRI: a dictionary learning approach
Authors: Abreu Rodolfo , Leal Alberto , Figueiredo Patrícia
Published: January 2019

Most fMRI studies of the brain’s intrinsic functional connectivity (FC) have assumed that this is static; however, it is now clear that it changes over time. This is particularly relevant in epilepsy, which is characterized by a continuous interchange between epileptic and normal brain states associated with the occurrence of epileptic activity. Interestingly, recurrent states of dynamic FC (dFC) have been found in fMRI data using unsupervised learning techniques, assuming either their sparse or non-sparse combination. Here, we propose an l1-norm regularized dictionary learning (l1-DL) approach for dFC state estimation, which allows an intermediate and flexible degree of sparsity in time, and demonstrate its application in the identification of epilepsy-related dFC states using simultaneous EEG-fMRI data. With this l1-DL approach, we aim to accommodate a potentially varying degree of sparsity upon the interchange between epileptic and non-epileptic dFC states. The simultaneous recording of the EEG is used to extract time courses representative of epileptic activity, which are incorporated into the fMRI dFC state analysis to inform the selection of epilepsy-related dFC states. We found that the proposed l1-DL method performed best at identifying epilepsy-related dFC states, when compared with two alternative methods of extreme sparsity (k-means clustering, maximum; and principal component analysis, minimum), as well as an l0-norm regularization framework (l0-DL), with a fixed amount of temporal sparsity. We further showed that epilepsy-related dFC states provide novel insights into the dynamics of epileptic networks, which go beyond the information provided by more conventional EEG-correlated fMRI analysis, and which were concordant with the clinical profile of each patient. In addition to its application in epilepsy, our study provides a new dFC state identification method of potential relevance for studying brain functional connectivity dynamics in general.
Influence of accuracy, repeatability and detection probability in the reliability of species-specific eDNA based approaches
Authors: Mauvisseau Quentin , Burian Alfred , Gibson Ceri , Brys Rein , Ramsey Andrew , Sweet Michael
Published: January 2019

Environmental DNA (eDNA) barcoding has a high potential to increase the cost-efficiency of species detection and monitoring in aquatic habitats. However, despite vast developments in the field, many published assays often lack detailed validation and there is little to no commonly (agreed upon) standardization of protocols. In this study, we evaluated the reliability of eDNA detection and quantification using published primers and assays targeting the Freshwater Pearl Mussel as a model organism. We first assessed limits of detection for two different target genes (COI and 16S) following the MIQE guidelines, and then tested the reliability of quantification in a double-blind mesocosm experiment. Our results reveal that different methodological indicators, namely accuracy, repeatability and detection probability affected the reliability of eDNA measurement at the different levels tested. The selection of the optimal analytical method was mainly determined by detection probability. Both the COI and 16S assays were highly specific for the targeted organism and showed similar accuracy and repeatability, whilst the limit of detection was clearly lower for the COI based approach. In contrast, the reliability of eDNA quantification hinged on repeatability, reflected by the scattering (r2 = 0.87) around the relationship between eDNA and mussel density in mesocosms. A bootstrapping approach, which allowed for the assignment of measures associated with repeatability of samples, revealed that variability between natural replicates (i.e. accuracy) strongly influenced the number of replicates required for a reliable species detection and quantification in the field.
Exosomes Cause Preterm Birth in Mice: Evidence for Paracrine Signaling in Pregnancy
Authors: Sheller-Miller Samantha , Trivedi Jayshil , Yellon Steven M. , Menon Ramkumar
Published: January 2019

Endocrine factors and signals of fetal organ maturation are reported determinants of birth timing. To test the hypothesis that paracrine signaling by exosomes are key regulators of parturition, maternal plasma exosomes from CD-1 mice were isolated and characterized throughout gestation and the biological pathways associated with differentially-expressed cargo proteins were determined. Results indicate that the shape and size of exosomes remained constant throughout gestation; however, a progressive increase in the quantity of exosomes carrying inflammatory mediators was observed from gestation day (E)5 to E19. In addition, the effects of late-gestation (E18) plasma exosomes derived from feto-maternal uterine tissues on parturition was determined. Intraperitoneal injection of E18 exosomes into E15 mice localized in maternal reproductive tract tissues and in intrauterine fetal compartments. Compared to controls that delivered at term, preterm birth occurred in exosome-treated mice on E18 and was preceded by increased inflammatory mediators on E17 in the cervix, uterus, and fetal membranes but not in the placenta. This effect was not observed in mice injected with early-gestation (E9) exosomes. This study provides evidence that exosomes function as paracrine mediators of labor and delivery.
Molecular structure and function of myelin protein P0 in membrane stacking
Authors: Raasakka Arne , Ruskamo Salla , Kowal Julia , Han Huijong , Baumann Anne , Myllykoski Matti , Fasano Anna , Rossano Rocco , Riccio Paolo , Bürck Jochen , Ulrich Anne S. , Stahlberg Henning , Kursula Petri
Published: January 2019

Compact myelin forms the basis of nerve insulation essential for higher vertebrates. Dozens of myelin membrane bilayers undergo tight stacking, and in the peripheral nervous system, this is partially enabled by myelin protein zero (P0). Consisting of an immunoglobulin (Ig)-like extracellular domain, a single transmembrane helix, and a cytoplasmic extension (P0ct), P0 harbours an important task in ensuring the integrity of compact myelin in the extracellular compartment, referred to as the intraperiod line. Several disease mutations resulting in peripheral neuropathies have been identified for P0, reflecting its physiological importance, but the arrangement of P0 within the myelin ultrastructure remains obscure. We performed a biophysical characterization of recombinant P0ct. P0ct contributes to the binding affinity between apposed cytoplasmic myelin membrane leaflets, which not only results in changes of the bilayer properties, but also potentially involves the arrangement of the Ig-like domains in a manner that stabilizes the intraperiod line. Transmission electron cryomicroscopy of native full-length P0 showed that P0 stacks lipid membranes by forming antiparallel dimers between the extracellular Ig-like domains. The zipper-like arrangement of the P0 extracellular domains between two membranes explains the double structure of the myelin intraperiod line. Our results contribute to the understanding of PNS myelin, the role of P0 therein, and the underlying molecular foundation of compact myelin stability in health and disease.
The relationship between oxidant levels and gut physiology in a litter-feeding termite
Authors: Sousa Gessica , Gandara Ana Caroline P. , Oliveira Pedro L. , Gomes Fabio M. , Bahia Ana Cristina , Machado Ednildo A.
Published: January 2019

The termite gut is an efficient decomposer of polyphenol-rich diets, such as lignocellulosic biomasses, and it has been proposed that non-enzymatic oxidative mechanisms could be involved with the digestive process in these animals. However, oxidant levels are completely unknown in termites, as well as protective mechanisms against oxidative damage to the termite gut and its microbiota. As the first step in investigating the role oxidants plays in termite gut physiology, this work presents oxidant levels, antioxidant enzymatic defenses, cell renewal and microbiota abundance along the litter-feeding termite Cornitermes cumulans gut compartments (foregut, midgut, mixed segment and hindgut p1, p3, p4, and p5 segments) and salivary glands. The results show variable levels of oxidants along the C. cumulans gut, the production of antioxidant enzymes, gut cell renewal as potential defenses against oxidative injuries and the profile of microbiota distribution (being predominantly inverse to oxidant levels). In this fashion, the oxidative challenges imposed by polyphenol-rich diet seem to be circumvented by the C. cumulans gut, ensuring efficiency of the digestive process together with preservation of tissue homoeostasis and microbiota growth. These results present new insights into the physicochemical properties of the gut in a litter-feeding termite, expanding our view in relation to termites’ digestive physiology.
Finding and analysing the minimum set of driver nodes required to control multilayer networks
Authors: Nacher Jose C. , Ishitsuka Masayuki , Miyazaki Shuichi , Akutsu Tatsuya
Published: January 2019

It is difficult to control multilayer networks in situations with real-world complexity. Here, we first define the multilayer control problem in terms of the minimum dominating set (MDS) controllability framework and mathematically demonstrate that simple formulas can be used to estimate the size of the minimum dominating set in multilayer (MDSM) complex networks. Second, we develop a new algorithm that efficiently identifies the MDSM in up to 6 layers, with several thousand nodes in each layer network. Interestingly, the findings reveal that the MDSM size for similar networks does not significantly differ from that required to control a single network. This result opens future directions for controlling, for example, multiple species by identifying a common set of enzymes or proteins for drug targeting. We apply our methods to 70 genome-wide metabolic networks across major plant lineages, unveiling some relationships between controllability in multilayer networks and metabolic functions at the genome scale.
Geoarchaeological Evidence of Middle-Age Tsunamis at Stromboli and Consequences for the Tsunami Hazard in the Southern Tyrrhenian Sea
Authors: Rosi M. , Levi S. T. , Pistolesi M. , Bertagnini A. , Brunelli D. , Cannavò V. , Di Renzoni A. , Ferranti F. , Renzulli A. , Yoon D.
Published: January 2019

Large-scale landslides at volcanic islands are one of the most dangerous geological phenomena, able to generate tsunamis whose effects can propagate far from the source. However, related deposits are scarcely preserved on-land in the geologic records, and are often difficult to be interpreted. Here we show the discovery of three unprecedented well-preserved tsunami deposits related to repeated flank collapses of the volcanic island of Stromboli (Southern Italy) occurred during the Late Middle Ages. Based on carbon datings, on stratigraphic, volcanological and archaeological evidence, we link the oldest, highest-magnitude investigated tsunami to the following rapid abandonment of the island which was inhabited at that time, contrary than previously thought. The destructive power of this event is also possibly related to a huge marine storm that devastated the ports of Naples in 1343 (200 km north of Stromboli) described by the famous writer Petrarch. The portrayed devastation can be potentially attributed to the arrival of multiple tsunami waves generated by a major landslide in Stromboli island, confirming the hypothetical hazard of these phenomena at a regional scale.
High Serum Uric Acid is Highly Associated with a Reduced Left Ventricular Ejection Fraction Rather than Increased Plasma B-type Natriuretic Peptide in Patients with Cardiovascular Diseases
Authors: Oki Yoshitsugu , Kawai Makoto , Minai Kosuke , Ogawa Kazuo , Inoue Yasunori , Morimoto Satoshi , Tanaka Toshikazu , Nagoshi Tomohisa , Ogawa Takayuki , Yoshimura Michihiro
Published: January 2019

High serum uric acid (UA) has been reported to be associated with left ventricular (LV) dysfunction; however, the relationship between UA and plasma B-type natriuretic peptide (BNP), a sensitive biomarker of heart failure, is still unclear. This study investigated their relationship to provide an accurate assessment of high UA. The study patients consisted of 3,077 subjects who underwent cardiac catheterization because of various cardiovascular disorders. Since the explanatory factors of multiple regression analysis were mostly confounding with each other, subgroup analysis was performed by quartering the study population using the respective risk factors and by covariance structure analysis. This analysis revealed that UA was almost always well associated with a reduced LV ejection fraction (LVEF), but generally not with BNP. UA was significantly associated with BNP in lean aged females, but not in obese adolescent males, although LVEF was significantly reduced in response to a high UA in both groups. A high UA is a direct risk factor for cardiac dysfunction from the perspective of BNP; however, augmentation of BNP in response to a high UA would likely be restricted among obese adolescent males. On the other hand, the observed LV systolic dysfunction, such as LVEF, reflects a high UA on an almost constant basis.
A Ras destabilizer KYA1797K overcomes the resistance of EGFR tyrosine kinase inhibitor in KRAS-mutated non-small cell lung cancer
Authors: Park Jieun , Cho Yong-Hee , Shin Wook-Jin , Lee Sang-Kyu , Lee JaeHeon , Kim Taehyung , Cha Pu-Hyeon , Yang Jee Sun , Cho Jaebeom , Min Do Sik , Han Gyoonhee , Lee Ho-Young , Choi Kang-Yell
Published: January 2019

The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population of patients. The KRAS mutations, which are identified in approximately 20% of NSCLC patients, have shown to be associated with the resistance to the EGFR tyrosine kinase inhibitors (TKIs). Currently, there is no clinically available targeted therapy which can effectively inhibit NSCLC tumors harboring KRAS mutations. This study aims to show the effectiveness of KYA1797K, a small molecule which revealed anti-cancer effect in colorectal cancer by destabilizing Ras via inhibiting the Wnt/β-catenin pathway, for the treatment of KRAS-mutated NSCLC. While erlotinib fail to have anti-transforming effect in NSCLC cell lines harboring KRAS mutations, KYA1797K effectively inhibited the Ras-ERK pathway in KRAS-mutant NSCLC cell lines. As a result, KYA1797K treatment suppressed the growth and transformation of KRAS mutant NSCLC cells and also induced apoptosis. Furthermore, KYA1797K effectively inhibited Kras-driven tumorigenesis in the KrasLA2 mouse model by suppressing the Ras-ERK pathway. The destabilization of Ras via inhibition of the Wnt/β-catenin pathway is a potential therapeutic strategy for KRAS-mutated NSCLC that is resistant to EGFR TKI.
Effects of control measures on the spread of LA-MRSA among Danish pig herds between 2006 and 2015 – a simulation study
Authors: Schulz Jana , Boklund Anette , Toft Nils , Halasa Tariq
Published: January 2019

There has been a rapid increase in Danish pig herds testing positive for livestock-associated Methicillin-resistant Staphylococcus aureus (LA-MRSA) since the first screening in 2008. Despite a national action plan to control LA-MRSA in the Danish pig population, 88% of pig herds tested positive in a 2016 cross-sectional study of 57 herds. The national action plan was initiated in April 2015 and aimed to reduce the spread of LA-MRSA among pig herds. However, its success is uncertain. We used a simulation model mimicking the spread of LA-MRSA among pig herds between 2006 and 2015 to evaluate the impact of control strategies if these had these been implemented in 2007 or 2010. The strategies were combinations of the following control measures: (1) a reduced number of herds using high-risk antibiotics, (2) a reduced probability of indirect transmission among herds via humans, (3) movement restrictions, and (4) voluntary eradication in 5–7.5% of the herds. Almost all tested control strategies simulated a reduction in the spread of LA-MRSA. The combination of two, three or four intervention strategies showed additive effects and led to larger reductions in the predicted herd prevalence. In addition, the prevalence of LA-MRSA-positive herds at the time when control measures were initiated influenced the effects of the control strategies. Combining the simulated control measures can be considered in future action plans to control LA-MRSA.
Author Correction: The relationship between plasma ferritin levels and body mass index among adolescents
Authors: Shattnawi Khulood K. , Alomari Mahmoud A. , Al-Sheyab Nihaya , Salameh Ayman Bani
Published: January 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Silicon increases the phosphorus availability of Arctic soils
Authors: Schaller Jörg , Faucherre Samuel , Joss Hanna , Obst Martin , Goeckede Mathias , Planer-Friedrich Britta , Peiffer Stefan , Gilfedder Benjamin , Elberling Bo
Published: January 2019

Phosphorus availability in soils is an important parameter influencing primary production in terrestrial ecosystems. Phosphorus limitation exists in many soils since a high proportion of soil phosphorus is stored in unavailable forms for plants, such as bound to iron minerals or stabilized organic matter. This is in spite of soils having a high amount of total soil phosphorus. The feasibility of silicon to mobilize phosphorus from strong binding sites of iron minerals has been shown for marine sediments but is less well studied in soils. Here we tested the effect of silicon on phosphorus mobilization for 143 Artic soils (representing contrasting soil characteristics), which have not been affected by agriculture or other anthropogenic management practices. In agreement with marine studies, silicon availabilities were significantly positive correlated to phosphorus mobilization in these soils. Laboratory experiments confirmed that silicon addition significantly increases phosphorus mobilization, by mobilizing Fe(II)-P phases from mineral surfaces. Silicon addition increased also soil respiration in phosphorus deficient soils. We conclude that silicon is a key component regulating mobilization of phosphorous in Arctic soils, suggesting that this may also be important for sustainable management of phosphorus availability in soils in general.
The co-transfer of plasmid-borne colistin-resistant genes mcr-1 and mcr-3.5, the carbapenemase gene blaNDM-5 and the 16S methylase gene rmtB from Escherichia coli
Authors: Long Haiyan , Feng Yu , Ma Ke , Liu Lu , McNally Alan , Zong Zhiyong
Published: January 2019

We found an unusual Escherichia coli strain with resistance to colistin, carbapenem and amikacin from sewage. We therefore characterized the strain and determined the co-transfer of the resistance determinants. Whole genome sequencing was performed using both Illumina HiSeq X10 and MinION sequencers. Short and long reads were subjected to de novo hybrid assembly. Sequence type, antimicrobial resistance genes and plasmid replicons were identified from the genome sequences. Phylogenetic analysis of all IncHI2 plasmids carrying mcr-1 available in GenBank was performed based on core genes. Conjugation experiments were performed. mcr-3.5 was cloned into E. coli DH5α. The strain belonged to ST410, a type with a global distribution. Two colistin-resistant genes, mcr-1.1 and mcr-3.5, a carbapenemase gene blaNDM-5, and a 16S methylase gene rmtB were identified on different plasmids of IncHI2(ST3)/IncN, IncP, IncX3 and IncFII, respectively. All of the four plasmids were self-transmissible and mcr-1.1, mcr-3.5, blaNDM-5 and rmtB were transferred together. mcr-1-carrying IncHI2 plasmids belonged to several sequence types with ST3 and ST4 being predominant. MIC of colistin (4 μg/ml) for DH5α containing mcr-3.5 was identical to that containing the original mcr-3 variant. In conclusion, carbapenem resistance, colistin resistance and high-level aminoglycoside resistance can be transferred together even when their encoding genes are not located on the same plasmid. The co-transfer of multiple clinically-important antimicrobial resistance represents a particular challenge for clinical treatment and infection control in healthcare settings. Isolates with resistance to both carbapenem and colistin are not restricted to a given sequence type but rather are diverse in clonal background, which warrants further surveillance. The amino acid substitutions of MCR-3.5 have not altered its activity against colistin.
Force sharing and force generation by two teams of elastically coupled molecular motors
Authors: Uçar Mehmet Can , Lipowsky Reinhard
Published: January 2019

Many active cellular processes such as long-distance cargo transport, spindle organization, as well as flagellar and ciliary beating are driven by molecular motors. These motor proteins act collectively and typically work in small teams. One particularly interesting example is two teams of antagonistic motors that pull a common cargo into opposite directions, thereby generating mutual interaction forces. Important issues regarding such multiple motor systems are whether or not motors from the same team share their load equally, and how the collectively generated forces depend on the single motor properties. Here we address these questions by introducing a stochastic model for cargo transport by an arbitrary number of elastically coupled molecular motors. We determine the state space of this motor system and show that this space has a rather complex and nested structure, consisting of multiple activity states and a large number of elastic substates, even for the relatively small system of two identical motors working against one antagonistic motor. We focus on this latter case because it represents the simplest tug-of-war that involves force sharing between motors from the same team. We show that the most likely motor configuration is characterized by equal force sharing between identical motors and that the most likely separation of these motors corresponds to a single motor step. These likelihoods apply to different types of motors and to different elastic force potentials acting between the motors. Furthermore, these features are observed both in the steady state and during the initial build-up of elastic strains. The latter build-up is non-monotonic and exhibits a maximum at intermediate times, a striking consequence of mutual unbinding of the elastically coupled motors. Mutual strain-induced unbinding also reduces the magnitude of the collectively generated forces. Our computational approach is quite general and can be extended to other motor systems such as motor teams working against an optical trap or mixed teams of motors with different single motor properties.
Remote sensing of zooplankton swarms
Authors: Basedow Sünnje L. , McKee David , Lefering Ina , Gislason Astthor , Daase Malin , Trudnowska Emilia , Egeland Einar Skarstad , Choquet Marvin , Falk-Petersen Stig
Published: January 2019

Zooplankton provide the key link between primary production and higher levels of the marine food web and they play an important role in mediating carbon sequestration in the ocean. All commercially harvested fish species depend on zooplankton populations. However, spatio-temporal distributions of zooplankton are notoriously difficult to quantify from ships. We know that zooplankton can form large aggregations that visibly change the color of the sea, but the scale and mechanisms producing these features are poorly known. Here we show that large surface patches (>1000 km2) of the red colored copepodCalanus finmarchicuscan be identified from satellite observations of ocean color. Such observations provide the most comprehensive view of the distribution of a zooplankton species to date, and alter our understanding of the behavior of this key zooplankton species. Moreover, our findings suggest that high concentrations of astaxanthin-rich zooplankton can degrade the performance of standard blue-green reflectance ratio algorithms in operational use for retrieving chlorophyll concentrations from ocean color remote sensing.
Anomalous transverse resistance in 122-type iron-based superconductors
Authors: Lv Yangyang , Dong Yu , Lu Dachuan , Tian Wanghao , Xu Zuyu , Chen Wei , Zhou Xianjing , Yuan Jie , Jin Kui , Bao Song , Li Shichao , Wen Jinsheng , Chibotaru Liviu F. , Schwarz Tobias , Kleiner Reinhold , Koelle Dieter , Li Jun , Wang Huabing , Wu Peiheng
Published: January 2019

The study of transverse resistance of superconductors is essential to understand the transition to superconductivity. Here, we investigated the in-plane transverse resistance of Ba0.5K0.5Fe2As2 superconductors, based on ultra-thin micro-bridges fabricated from optimally doped single crystals. An anomalous transverse resistance was found at temperatures around the superconducting transition, although magnetic order or structure distortion are absent in the optimal doping case. With the substitution of magnetic and nonmagnetic impurities into the superconducting layer, the anomalous transverse resistance phenomenon is dramatically enhanced. We find that anisotropic scattering or the superconducting electronic nematic state related with the superconducting transition may contribute to this phenomenon.
Phenotypic analysis of Myo10 knockout (Myo10tm2/tm2) mice lacking full-length (motorized) but not brain-specific headless myosin X
Authors: Bachg Anne C. , Horsthemke Markus , Skryabin Boris V. , Klasen Tim , Nagelmann Nina , Faber Cornelius , Woodham Emma , Machesky Laura M. , Bachg Sandra , Stange Richard , Jeong Hyun-Woo , Adams Ralf H. , Bähler Martin , Hanley Peter J.
Published: January 2019

We investigated the physiological functions of Myo10 (myosin X) using Myo10 reporter knockout (Myo10tm2) mice. Full-length (motorized) Myo10 protein was deleted, but the brain-specific headless (Hdl) isoform (Hdl-Myo10) was still expressed in homozygous mutants. In vitro, we confirmed that Hdl-Myo10 does not induce filopodia, but it strongly localized to the plasma membrane independent of the MyTH4-FERM domain. Filopodia-inducing Myo10 is implicated in axon guidance and mice lacking the Myo10 cargo protein DCC (deleted in colorectal cancer) have severe commissural defects, whereas MRI (magnetic resonance imaging) of isolated brains revealed intact commissures in Myo10tm2/tm2 mice. However, reminiscent of Waardenburg syndrome, a neural crest disorder, Myo10tm2/tm2 mice exhibited pigmentation defects (white belly spots) and simple syndactyly with high penetrance (>95%), and 24% of mutant embryos developed exencephalus, a neural tube closure defect. Furthermore, Myo10tm2/tm2 mice consistently displayed bilateral persistence of the hyaloid vasculature, revealed by MRI and retinal whole-mount preparations. In principle, impaired tissue clearance could contribute to persistence of hyaloid vasculature and syndactyly. However, Myo10-deficient macrophages exhibited no defects in the phagocytosis of apoptotic or IgG-opsonized cells. RNA sequence analysis showed that Myo10 was the most strongly expressed unconventional myosin in retinal vascular endothelial cells and expression levels increased 4-fold between P6 and P15, when vertical sprouting angiogenesis gives rise to deeper layers. Nevertheless, imaging of isolated adult mutant retinas did not reveal vascularization defects. In summary, Myo10 is important for both prenatal (neural tube closure and digit formation) and postnatal development (hyaloid regression, but not retinal vascularization).
Off-target based drug repurposing opportunities for tivantinib in acute myeloid leukemia
Authors: Kuenzi Brent M. , Remsing Rix Lily L. , Kinose Fumi , Kroeger Jodi L. , Lancet Jeffrey E. , Padron Eric , Rix Uwe
Published: January 2019

GSK3α has been identified as a new target in the treatment of acute myeloid leukemia (AML). However, most GSK3 inhibitors lack specificity for GSK3α over GSK3β and other kinases. We have previously shown in lung cancer cells that GSK3α and to a lesser extent GSK3β are inhibited by the advanced clinical candidate tivantinib (ARQ197), which was designed as a MET inhibitor. Thus, we hypothesized that tivantinib would be an effective therapy for the treatment of AML. Here, we show that tivantinib has potent anticancer activity across several AML cell lines and primary patient cells. Tivantinib strongly induced apoptosis, differentiation and G2/M cell cycle arrest and caused less undesirable stabilization of β-catenin compared to the pan-GSK3 inhibitor LiCl. Subsequent drug combination studies identified the BCL-2 inhibitor ABT-199 to synergize with tivantinib while cytarabine combination with tivantinib was antagonistic. Interestingly, the addition of ABT-199 to tivantinib completely abrogated tivantinib induced β-catenin stabilization. Tivantinib alone, or in combination with ABT-199, downregulated anti-apoptotic MCL-1 and BCL-XL levels, which likely contribute to the observed synergy. Importantly, tivantinib as single agent or in combination with ABT-199 significantly inhibited the colony forming capacity of primary patient AML bone marrow mononuclear cells. In summary, tivantinib is a novel GSK3α/β inhibitor that potently kills AML cells and tivantinib single agent or combination therapy with ABT-199 may represent attractive new therapeutic opportunities for AML.
Human pluripotent stem cell-derived alveolar epithelial cells are alternatives for in vitro pulmotoxicity assessment
Authors: Heo Hye-Ryeon , Kim Jeeyoung , Kim Woo Jin , Yang Se-Ran , Han Seon-Sook , Lee Seong Joon , Hong Yoonki , Hong Seok-Ho
Published: January 2019

Human pluripotent stem cell (hPSC)-derived alveolar epithelial cells (AECs) provide new opportunities for understanding lung development and the treatment of pulmonary diseases. However, toxicity assessments using hPSC-AECs have not been undertaken. In this study, we generated functional AECs from hPSCs and evaluated their inflammatory and apoptotic responses to cadmium (Cd) exposure (1, 5, and 10 μM) for 24 h compared with the human bronchial epithelial cell line (BEAS-2B) and primary AECs as controls. Our data showed that Cd (10 μM) treatment induced substantial inflammatory responses and apoptosis in BEAS-2B cells, but not in both hPSC-AECs and primary AECs. Interestingly, conditioned medium from AEC cultures significantly alleviated apoptotic and inflammatory responses to Cd exposure in BEAS-2B cells. Using cytokine arrays, several potential factors secreted from hPSC-AECs and primary AECs were detected and may be involved in reducing Cd-induced cytotoxicity. We also observed higher expression of surfactant proteins B and C in both hPSC-AECs and primary AECs, which may contribute to protection against Cd-induced cytotoxicity. These results suggested that hPSC-AECs phenotypically and functionally resemble primary AECs and could be more biologically relevant alternatives for evaluating the pathological contribution of confirmed or potential pulmotoxic materials included in smoking and microdust.
Liver Derived FGF21 Maintains Core Body Temperature During Acute Cold Exposure
Authors: Ameka Magdalene , Markan Kathleen R. , Morgan Donald A. , BonDurant Lucas D. , Idiga Sharon O. , Naber Meghan C. , Zhu Zhiyong , Zingman Leonid V. , Grobe Justin L. , Rahmouni Kamal , Potthoff Matthew J.
Published: January 2019

Fibroblast Growth Factor 21 (FGF21) elicits an array of metabolic effects. However, the physiological role of FGF21 during thermal challenges is not clear. In this study, we assessed the tissue source of FGF21 and its site of action to regulate core body temperature in response to cold. Using mice lacking FGF21 specifically in the liver (FGF21 LivKO) or adipose tissues (FGF21 AdipoKO), we performed a series of cold exposure studies to examine the tissue specific induction of FGF21 in response to cold. We also examined the physiological site of FGF21 action during cold exposure by impairing FGF21 signaling to adipose tissues or the central nervous system (CNS) using genetic ablation of the FGF21 co-receptor β-klotho in adipose tissues (KLB AdipoKO) or pharmacological blockage of FGF21 signaling. We found that only liver-derived FGF21 enters circulation during acute cold exposure and is critical for thermoregulation. While FGF21 signaling directly to adipose tissues during cold is dispensable for thermoregulation, central FGF21 signaling is necessary for maximal sympathetic drive to brown adipose tissue to maintain thermoregulation during cold. These data demonstrate a previously unrecognized role for FGF21 in the maintenance of body temperature in response to cold.
Potential Spatial Distribution of the Newly Introduced Long-horned Tick, Haemaphysalis longicornis in North America
Authors: Raghavan R. K. , Barker S. C. , Cobos M. E. , Barker D. , Teo E. J. M. , Foley D. H. , Nakao R. , Lawrence K. , Heath A. C. G. , Peterson A. T.
Published: January 2019

The North American distributional potential of the recently invaded tick, Haemaphysalis longicornis, was estimated using occurrence data from its geographic range in other parts of the world and relevant climatic data sets. Several hundred candidate models were built using a correlative maximum entropy approach, and best-fitting models were selected based on statistical significance, predictive ability, and complexity. The median of the best-fitting models indicates a broad potential distribution for this species, but restricted to three sectors—the southeastern United States, the Pacific Northwest, and central and southern Mexico.
Gain–loss situation modulates neural responses to self–other decision making under risk
Authors: Zhang Xiangyi , Li Shijia , Liu Yongfang , Chen Xiyou , Shang Xuesong , Qi Fangzhu , Wang Xiaoyan , Guo Xiuyan , Chen Jie
Published: January 2019

Although self–other behavioral differences in decision making under risk have been observed in some contexts, little is known about the neural mechanisms underlying such differences. Using functional magnetic resonance imaging (fMRI) and the cups task, in which participants choose between risky and sure options for themselves and others in gain and loss situations, we found that people were more risk-taking when making decisions for themselves than for others in loss situations but were equally risk-averse in gain situations. Significantly stronger activations were observed in the dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) when making decisions for the self than for others in loss situations but not in gain situations. Furthermore, the activation in the dmPFC was stronger when people made sure choices for others than for themselves in gain situations but not when they made risky choices, and was both stronger when people made sure and risky choices for themselves than for others in loss situations. These findings suggest that gain–loss situation modulates self–other differences in decision making under risk, and people are highly likely to differentiate the self from others when making decisions in loss situations.
Cerebrospinal fluid from Alzheimer’s disease patients as an optimal formulation for therapeutic application of mesenchymal stem cells in Alzheimer’s disease
Authors: Lee Jeongmin , Kwon Soo Jin , Kim Jang Hoon , Jang Hyemin , Lee Na Kyung , Hwang Jung Won , Kim Jong Hwa , Chang Jong Wook , Na Duk L.
Published: January 2019

Mesenchymal stem cells (MSCs) have emerged as one of the promising treatment options for Alzheimer’s disease (AD). Although many studies have investigated on the efficacy of MSCs in AD, how MSCs actually change following exposure to the AD environment has not been studied extensively. In this study, we investigated on the potential of AD patient-cerebrospinal fluid (CSF) samples to be used as a formulation of MSCs and its application in AD therapeutics. When Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) were stored in the CSF of AD patients, the stemness of WJ-MSCs was preserved. Furthermore, several genes were upregulated following storage in AD CSF. This signified the therapeutic potential of CSF formulation for AD therapy. Overall, these findings suggest that CSF from AD patients can be an optimal source for MSC formulation.
A gene expression signature in developing Purkinje cells predicts autism and intellectual disability co-morbidity status
Authors: Clifford Harry , Dulneva Anna , Ponting Chris P. , Haerty Wilfried , Becker Esther B. E.
Published: January 2019

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease whose underpinning molecular mechanisms and neural substrates are subject to intense scrutiny. Interestingly, the cerebellum has emerged as one of the key brain regions affected in ASD. However, the genetic and molecular mechanisms that link the cerebellum to ASD, particularly during development, remain poorly understood. To gain insight into the genetic and molecular mechanisms that might link the cerebellum to ASD, we analysed the transcriptome dynamics of a developing cell population highly enriched for Purkinje cells of the mouse cerebellum across multiple timepoints. We identified a single cluster of genes whose expression is positively correlated with development and which is enriched for genes associated with ASD. This ASD-associated gene cluster was specific to developing Purkinje cells and not detected in the mouse neocortex during the same developmental period, in which we identified a distinct temporally regulated ASD gene module. Furthermore, the composition of ASD risk genes within the two distinct clusters was significantly different in their association with intellectual disability (ID), consistent with the existence of genetically and spatiotemporally distinct endophenotypes of ASD. Together, our findings define a specific cluster of ASD genes that is enriched in developing PCs and predicts co-morbidity status.
Subcutaneous Inoculation of Echinococcus multilocularis Induces Delayed Regeneration after Partial Hepatectomy
Authors: Apaer Shadike , Tuxun Tuerhongjiang , Zhang Heng , Aierken Amina , Li Tao , Zhao Jin-Ming , Wen Hao
Published: January 2019

Alveolar echinococcosis (AE) is caused by the larval stage of echinococcus multilocularis (E. multilocularis), and hepatectomy is the main modality in hepatic AE patients. Liver regeneration after partial hepatectomy (PHx) in such patients is challenging, and further investigation is needed. Thus far, knowledge regarding the possible impact of E. multilocularis on liver regeneration after PHx is limited. Herein, a subcutaneous infection model of E. multilocularis was developed in C57 BL/6 mice, and after 3 months, PHx was performed. Plasma and liver samples were harvested under inhalational isofluorane (2%) anaesthesia at designated post-PHx time points (0, 24, 48, 96 and 168 h). The parameters included the future remnant liver/body weight ratio (FLR/BW), liver function tests (AST and ALT) and related cytokines (TNF-α, IL-6, Factor V, HMGB1, TGF-β, TSP-1, and TLR4) and proteins (MyD88 and STAT3). To assess the proliferation intensity of hepatocytes, BrdU, Ki67 and PAS staining were carried out in regenerated liver tissue. The FLR/BW in the infected group from 48 h after surgery was lower than that in the control group. The BrdU positive hepatocyte proportions reached their peak at 48 h in the control group and 96 h in the infected group and then gradually decreased. During the first 48 h after surgery, both the AST and ALT levels in the infected group were lower; however, these levels were altered from 96 h after surgery. In the infected group, the concentrations and mRNA expression levels of the pre-inflammatory cytokines TNF-α and IL-6 demonstrated a delayed peak. Moreover, post-operatively, the TGF-β and TSP-1 levels showed high levels in the infected group at each different time-point compared to those in the control group; however, high levels of TGF-β were observed at 96 h in the control group. The MyD88 and STAT3 protein expression levels in the infected group were markedly higher than those in the control group 96 h after surgery. Delayed liver regeneration after PHx was observed in the C57 BL/6 mice with the subcutaneous infection of E. multilocularis in the current study. This phenomenon could be partially explained by the alteration in the pro-inflammatory cytokines in the immunotolerant milieu induced by chronic E. multilocularis infection.
The structure of the nucleoprotein of Influenza D shows that all Orthomyxoviridae nucleoproteins have a similar NPCORE, with or without a NPTAIL for nuclear transport
Authors: Donchet Amélie , Oliva Justine , Labaronne Alice , Tengo Laura , Miloudi Myriam , C.A. Gerard Francine , Mas Caroline , Schoehn Guy , W.H. Ruigrok Rob , Ducatez Mariette , Crépin Thibaut
Published: January 2019

This paper focuses on the nucleoprotein (NP) of the newly identified member of the Orthomyxoviridae family, Influenza D virus. To date several X-ray structures of NP of Influenza A (A/NP) and B (B/NP) viruses and of infectious salmon anemia (ISA/NP) virus have been solved. Here we purified, characterized and solved the X-ray structure of the tetrameric D/NP at 2.4 Å resolution. The crystal structure of its core is similar to NP of other Influenza viruses. However, unlike A/NP and B/NP which possess a flexible amino-terminal tail containing nuclear localization signals (NLS) for their nuclear import, D/NP possesses a carboxy-terminal tail (D/NPTAIL). We show that D/NPTAIL harbors a bipartite NLS and designed C-terminal truncated mutants to demonstrate the role of D/NPTAIL for nuclear transport.
Thermodynamic stability of magnetic states of monovacancy in graphene revealed by ab initio molecular dynamics simulations
Authors: Gao Fei , Gao Shiwu
Published: January 2019

The stability of magnetic states is essential for potential spintronic applications. Here we report on the thermal stability of magnetic states of monovacancy graphene using ab initio molecular dynamics simulations. At room temperature, thermal fluctuations of the graphene lattice induce a rapid magnetic switching between two states with a high and low magnetic moment, indicating that due to the instability of the atomic structure of the vacancy, the associated magnetic moment is thermodynamically unstable. Lowering the temperature can significantly reduce the rate of the switching process and enhance the resident time on the high magnetic state. It stabilizes in the high magnetic state at as low as 30 K. Analyzing the atomic trajectories and the instant electronic structures confirms that these two magnetic states in MD simulations correspond to the magnetic and nonmagnetic states reported in the literatures. Such fluctuations of local magnetic moments are associated with the vertical displacement of the carbon atoms with the unsaturated dangling bond. This study reveals the dynamical correlation between atomic movement and the magnetic switching, and a comprehensive picture of vacancy magnetism in graphene. It has implications in graphene based spintronic devices.