bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractThere 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.
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

AbstractPhosphorus 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

AbstractWe 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

AbstractMany 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

AbstractZooplankton 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

AbstractThe 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

AbstractWe 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

AbstractGSK3α 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

AbstractHuman 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

AbstractFibroblast 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

AbstractThe 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

AbstractAlthough 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

AbstractMesenchymal 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.