bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lineage tracing of acute myeloid leukemia reveals the impact of hypomethylating agents on chemoresistance selection
Authors: Caiado Francisco , Maia-Silva Diogo , Jardim Carolina , Schmolka Nina , Carvalho Tânia , Reforço Cláudia , Faria Rita , Kolundzija Branka , Simões André E. , Baubec Tuncay , Vakoc Christopher R. , da Silva Maria Gomes , Manz Markus G. , Schumacher Ton N. , Norell Håkan , Silva-Santos Bruno 
Published: November 2019

AbstractChemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. Here, we develop an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the AML population dynamics and associated molecular determinants underpinning chemoresistance development. We find that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors (DNMTi, hypomethylating drugs) prevents chemoresistant relapses. Mechanistically, DNMTi suppresses the outgrowth of a pre-determined set of chemoresistant AML clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. Importantly, we confirm the capacity of DNMTi combination to suppress stemness-dependent chemoresistance development in xenotransplantation models and primary AML patient samples. Together, these results support the potential of DNMTi combination treatment to circumvent the development of chemorefractory AML relapses.
Quasi Pd1Ni single-atom surface alloy catalyst enables hydrogenation of nitriles to secondary amines
Authors: Wang Hengwei , Luo Qiquan , Liu Wei , Lin Yue , Guan Qiaoqiao , Zheng Xusheng , Pan Haibin , Zhu Junfa , Sun Zhihu , Wei Shiqiang , Yang Jinlong , Lu Junling 
Published: November 2019

AbstractHydrogenation of nitriles represents as an atom-economic route to synthesize amines, crucial building blocks in fine chemicals. However, high redox potentials of nitriles render this approach to produce a mixture of amines, imines and low-value hydrogenolysis byproducts in general. Here we show that quasi atomic-dispersion of Pd within the outermost layer of Ni nanoparticles to form a Pd1Ni single-atom surface alloy structure maximizes the Pd utilization and breaks the strong metal-selectivity relations in benzonitrile hydrogenation, by prompting the yield of dibenzylamine drastically from ∼5 to 97% under mild conditions (80 °C; 0.6 MPa), and boosting an activity to about eight and four times higher than Pd and Pt standard catalysts, respectively. More importantly, the undesired carcinogenic toluene by-product is completely prohibited, rendering its practical applications, especially in pharmaceutical industry. Such strategy can be extended to a broad scope of nitriles with high yields of secondary amines under mild conditions.
Conditional quorum-sensing induction of a cyanide-insensitive terminal oxidase stabilizes cooperating populations of Pseudomonas aeruginosa
Authors: Yan Huicong , Asfahl Kyle L. , Li Na , Sun Feng , Xiao Junwei , Shen Dongsheng , Dandekar Ajai A. , Wang Meizhen 
Published: November 2019

AbstractPseudomonas aeruginosa, an opportunistic pathogen of humans, uses quorum sensing (QS) to regulate the production of extracellular products that can benefit all members of the population.P. aeruginosacan police QS-deficient cheaters by producing hydrogen cyanide, which is also QS regulated; however, the mechanism by which cooperators selectively protect themselves from the toxicity of cyanide remained unresolved. Here, we show that a cyanide-insensitive terminal oxidase encoded bycioABprovides resistance to cyanide, but only in QS-proficient strains. QS-deficient cheaters do not activatecioABtranscription. QS-mediated regulation ofcioABexpression depends on production of both cyanide by cooperators (which is QS regulated) and reactive oxygen species (ROS) from cheaters (which is not QS regulated). This type of regulatory system allows cooperating populations to respond, via ROS, to the presence of cheaters, and might allow them to defer the substantial metabolic cost of policing until cheaters are present in the population.
Essentiality of fatty acid synthase in the 2D to anchorage-independent growth transition in transforming cells
Authors: Bueno Maria J. , Jimenez-Renard Veronica , Samino Sara , Capellades Jordi , Junza Alejandra , López-Rodríguez María Luz , Garcia-Carceles Javier , Lopez-Fabuel Irene , Bolaños Juan P. , Chandel Navdeep S. , Yanes Oscar , Colomer Ramon , Quintela-Fandino Miguel 
Published: November 2019

AbstractUpregulation of fatty acid synthase (FASN) is a common event in cancer, although its mechanistic and potential therapeutic roles are not completely understood. In this study, we establish a key role of FASN during transformation. FASN is required for eliciting the anaplerotic shift of the Krebs cycle observed in cancer cells. However, its main role is to consume acetyl-CoA, which unlocks isocitrate dehydrogenase (IDH)-dependent reductive carboxylation, producing the reductive power necessary to quench reactive oxygen species (ROS) originated during the switch from two-dimensional (2D) to three-dimensional (3D) growth (a necessary hallmark of cancer). Upregulation of FASN elicits the 2D-to-3D switch; however, FASN's synthetic product palmitate is dispensable for this process since cells satisfy their fatty acid requirements from the media. In vivo, genetic deletion or pharmacologic inhibition of FASN before oncogenic activation prevents tumor development and invasive growth. These results render FASN as a potential target for cancer prevention studies.
Synergized regulation of NK cell education by NKG2A and specific Ly49 family members
Authors: Zhang Xiaoqian , Feng Jin , Chen Shasha , Yang Haoyan , Dong Zhongjun 
Published: November 2019

AbstractMice lacking MHC class-I (MHC-I) display severe defects in natural killer (NK) cell functional maturation, a process designated as “education”. Whether self-MHC-I specific Ly49 family receptors and NKG2A, which are closely linked within the NK gene complex (NKC) locus, are essential for NK cell education is still unclear. Here we show, using CRISPR/Cas9-mediated gene deletion, that mice lacking all members of the Ly49 family exhibit a moderate defect in NK cell activity, while mice lacking only two inhibitory Ly49 members, Ly49C and Ly49I, have comparable phenotypes. Furthermore, the deficiency of NKG2A, which recognizes non-classical MHC-Ib molecules, mildly impairs NK cell function. Notably, the combined deletion of NKG2A and the Ly49 family severely compromises the ability of NK cells to mediate “missing-self” and “induced-self” recognition. Therefore, our data provide genetic evidence supporting that NKG2A and the inhibitory members of Ly49 family receptors synergize to regulate NK cell education.
Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis
Authors: Schmidt Matthias , Wiese Sebastian , Adak Volkan , Engler Jonas , Agarwal Shubhangi , Fritz Günter , Westermark Per , Zacharias Martin , Fändrich Marcus 
Published: November 2019

AbstractATTR amyloidosis is one of the worldwide most abundant forms of systemic amyloidosis. The disease is caused by the misfolding of transthyretin protein and the formation of amyloid deposits at different sites within the body. Here, we present a 2.97 Å cryo electron microscopy structure of a fibril purified from the tissue of a patient with hereditary Val30Met ATTR amyloidosis. The fibril consists of a single protofilament that is formed from an N-terminal and a C-terminal fragment of transthyretin. Our structure provides insights into the mechanism of misfolding and implies the formation of an early fibril state from unfolded transthyretin molecules, which upon proteolysis converts into mature ATTR amyloid fibrils.
Quantum simulation of chemistry with sublinear scaling in basis size
Authors: Babbush Ryan , Berry Dominic W. , McClean Jarrod R. , Neven Hartmut 
Published: November 2019

AbstractWe present a quantum algorithm for simulating quantum chemistry with gate complexity $$\tilde {\cal{O}}(N^{1/3}\eta ^{8/3})$$

O

̃

(

N

1
∕
3

η

8
∕
3

)

where η is the number of electrons and N is the number of plane wave orbitals. In comparison, the most efficient prior algorithms for simulating electronic structure using plane waves (which are at least as efficient as algorithms using any other basis) have complexity $$\tilde {\cal{O}}(N^{8/3}{\mathrm{/}}\eta ^{2/3})$$

O

̃

(

N

8
∕
3

∕

η

2
∕
3

)

. We achieve our scaling in first quantization by performing simulation in the rotating frame of the kinetic operator using interaction picture techniques. Our algorithm is far more efficient than all prior approaches when N ≫ η, as is needed to suppress discretization error when representing molecules in the plane wave basis, or when simulating without the Born-Oppenheimer approximation.
Travel times to hospitals in Australia
Authors: Barbieri Sebastiano , Jorm Louisa 
Published: November 2019

AbstractTravel time to hospital is a key measure of health service accessibility, and impacts patients’ experiences of care and health outcomes. Methods used to estimate travel time vary across studies. In Australia the smallest geographical areas defined by the Australian Bureau of Statistics for the release of population counts are mesh blocks (MBs) and the smallest geographical areas for the release of health-related statistics are statistical areas level 2 (SA2). SA2s are built up from whole MBs. This project used the Open Source Routing Machine (OSRM) HTTP server to compute estimated travel times between the centroid of each inhabited MB and each hospital in Australia, as well as the shortest travel times between MBs and any hospital. By computing population-weighted averages across MBs, the average travel times to hospitals and the shortest travel time to any hospital were estimated for each SA2. This dataset will promote consistency across studies investigating geographic influences on health care in Australia, and the methods are applicable to generating similar datasets for other countries.
Chaotic synchronization of two optical cavity modes in optomechanical systems
Authors: Yang Nan , Miranowicz Adam , Liu Yong-Chun , Xia Keyu , Nori Franco 
Published: November 2019

AbstractThe synchronization of the motion of microresonators has attracted considerable attention. In previous studies, the microresonators for synchronization were studied mostly in the linear regime. While the important problem of synchronizing nonlinear microresonators was rarely explored. Here we present theoretical methods to synchronize the motions of chaotic optical cavity modes in an optomechanical system, where one of the optical modes is strongly driven into chaotic motion and transfers chaos to other weakly driven optical modes via a common mechanical resonator. This mechanical mode works as a common force acting on each optical mode, which, thus, enables the synchronization of states. We find that complete synchronization can be achieved in two identical chaotic cavity modes. For two arbitrary nonidentical chaotic cavity modes, phase synchronization can also be achieved in the strong-coupling small-detuning regime.
Wideband and Large Angle Electromagnetically Induced Transparency by the Equivalent Transmission Line in a Metasurface
Authors: Ning Renxia , Li Dekai , Yang Tianlong , Chen Zhenhai , Qian Hongwen 
Published: November 2019

AbstractA classical structure for a U-shaped metasurface exhibiting a wideband and large angle electromagnetically induced transparency (EIT) effect in the terahertz range is proposed. One horizontal and two vertical strips, which represent the bright and dark modes, respectively, are created for the U-shaped structure. The finite integration time domain (FITD) and equivalent circuit method are compared with the EIT result. The EIT effect is affected by the length of the vertical bar and by the distance from the vertical bar to the symmetry axis. The results show that the asymmetry of the main structure in the x and y axes makes it easier to achieve the EIT effect. In addition, by changing the incident angle, the EIT effect always exists until the angle of the incidental electromagnetic wave is 85 degrees. These results have many potential applications for terahertz filtering, large-angle switching and sensors.
Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice
Authors: Dornbos Peter , Jurgelewicz Amanda , Fader Kelly A. , Williams Kurt , Zacharewski Timothy R. , LaPres John J. 
Published: November 2019

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.
Mesoporous bimetallic Fe/Co as highly active heterogeneous Fenton catalyst for the degradation of tetracycline hydrochlorides
Authors: Li Junchao , Li Xuhua , Han Jindong , Meng Fansheng , Jiang Jinyuan , Li Jiao , Xu Chunlian , Li Yun 
Published: November 2019

AbstractMesoporous bimetallic Fe/Co was prepared as a Fenton-like catalyst to degrade the tetracycline hydrochlorides (TC). The nanocasting strategy with KIT-6 as a hard template was carried out to synthesize the mesoporous bimetallic catalyst. The mesoporous bimetallic Fe/Co catalyst was characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption isotherms, and Brunauer-Emmett-Teller (BET) method. The results showed that the catalyst has significant nanofeatures; the surface area, pore size, and particle size were 113.8 m2g−1, 4 nm, and 10 nm, respectively. In addition, the effects of the operating parameters, such as the iron-to-cobalt ratio, pH, H2O2, and initial TC concentrations on its catalytic performance were investigated. The best operating parameters were as follows: iron-to-cobalt ratio = 2:1 to 1:1, pH = 5–9, H2O2: 30 mmol, initial TC less than 30 mg/L. Furthermore, the mesoporous bimetallic Fe/Co showed a good performance for degrading TC, achieving a removal rate of 86% of TC after 3 h under the reaction conditions of H2O2 = 30 mmol, mesoporous bimetallic Fe/Co = 0.6 g/L, TC = 30 mg/L, pH = 7.0, and temperature = 25.5 °C. The mesoporous bimetallic Fe/Co catalyst shows good stability and reusability. This work demonstrated that mesoporous bimetallic Fe/Co has excellent catalytic efficiency, smaller amounts of leached ions, and wider pH range, which enhance its potential applications.
Aluminium incorporation in polar, semi- and non-polar AlGaN layers: a comparative study of x-ray diffraction and optical properties
Authors: Dinh Duc V. , Hu Nan , Honda Yoshio , Amano Hiroshi , Pristovsek Markus 
Published: November 2019

AbstractGrowth of AlxGa1−xN layers (0 ≤ x ≤ 1) simultaneously on polar (0001), semipolar ($$10\bar{{\rm{1}}}$$
10

1
¯

3) and ($$11\bar{{\rm{2}}}2$$
11

2
¯

2
), as well as nonpolar ($$10\bar{{\rm{1}}}0$$
10

1
¯

0
) and ($$11\bar{{\rm{2}}}0$$
11

2
¯

0
) AlN templates, which were grown on planar sapphire substrates, has been investigated by metal-organic vapour phase epitaxy. By taking into account anisotropic in-plane strain of semi- and non-polar layers, their aluminium incorporation has been determined by x-ray diffraction analysis. Optical emission energy of the layers was obtained from room-temperature photoluminescence spectra, and their effective bandgap energy was estimated from room-temperature pseudo-dielectric functions. Both x-ray diffraction and optical data consistently show that aluminium incorporation is comparable on the polar, semi- and non-polar planes.
Extracellular vesicle integrins act as a nexus for platelet adhesion in cerebral microvessels
Authors: Bagi Zsolt , Couch Yvonne , Broskova Zuzana , Perez-Balderas Francisco , Yeo Tianrong , Davis Simon , Fischer Roman , Sibson Nicola R. , Davis Benjamin G. , Anthony Daniel C. 
Published: November 2019

AbstractCirculating extracellular vesicles (EVs) regulate signaling pathways via receptor-ligand interactions and content delivery, after attachment or internalization by endothelial cells. However, they originate from diverse cell populations and are heterogeneous in composition. To determine the effects of specific surface molecules, the use of synthetic EV mimetics permits the study of specific EV receptor-ligand interactions. Here, we used endogenous EVs derived from the circulation of rats, as well as ligand-decorated synthetic microparticles (MPs) to examine the role of integrin αvβ3 in platelet adhesion under flow in structurally intact cerebral arteries. At an intraluminal pressure of 50 mmHg and flow rate of 10 µl/min, platelets were delivered to the artery lumen and imaged with whole-field fluorescent microscopy. Under basal conditions very few platelets bound to the endothelium. However, adhesion events were markedly increased following the introduction of arginine-glycine-aspartate (RGD)-labelled synthetic MPs or endogenously-derived EVs from experimental stroke animals carrying excess RGD proteins, including vitronectin, CD40-ligand and thrombospondin-1. These data, which were generated in a dynamic and physiologically relevant system, demonstrate the importance of vesicle-carried RGD ligands in platelet adherence to the cerebrovascular endothelium and highlight the ability of synthetic EVs to isolate and identify key components of the molecular handshake between EVs and their targets.
High prevalence of obesity-related hypertension among adults aged 40 to 79 years in Southwest China
Authors: Zhang Yang , Hou Li-Sha , Tang Wei-Wei , Xu Fan , Xu Rong-Hua , Liu Xin , Liu Ya , Liu Jian-Xiong , Yi Yan-Jing , Hu Tai-Shang , Hu Rong , Wang Tzung-Dau , Huang Xiao-Bo 
Published: November 2019

AbstractThis study aimed to assess the prevalence and related factors of obesity-related hypertension among adults aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a multi-stage, stratified sampling method was conducted on 10,589 people aged 40 to 79 years and living in Chengdu and Chongqing investigated by using a questionnaire and performing physical and biochemical measurements. The prevalence of obesity-related hypertension and hypertension overall (systolic ≥130 mmHg and/or diastolic ≥80 mmHg or treated hypertension) was 22.8% and 57.4%, respectively, among all participants. For obesity-related hypertension, the prevalence was higher in women than in men (24.7% versus 19.4%, p < 0.001). For people in the age ranges of 40–49, 50–59, 60–69, and ≥70, the prevalence of obesity-related hypertension were 11.8%, 22.6%, 30.7%, and 36.6%, respectively. Participants with obesity-related hypertension as opposed to those with non-obesity-related hypertension had a higher prevalence of hypertriglyceridemia, high low-density lipoprotein cholesterolemia, diabetes, and hyperuricemia (all p < 0.05). Multivariate logistic regression analysis showed that age, female gender, current smoking, hypertriglyceridemia, diabetes and family history of hypertension were all positively correlated with obesity-related hypertension, whereas higher education level and having spouse were negatively correlated with obesity-related hypertension. The prevalence of obesity-related hypertension was high among adults aged 40 to 79 years in Southwest China. Cardiometabolic abnormalities among participants with obesity-related hypertension were more serious and frequently present than in those with non-obesity-related hypertension. Aggressive and holistic strategies aiming at the prevention and treatment of obesity-related hypertension are needed.
Developmental conditions modulate DNA methylation at the glucocorticoid receptor gene with cascading effects on expression and corticosterone levels in zebra finches
Authors: Jimeno Blanca , Hau Michaela , Gómez-Díaz Elena , Verhulst Simon 
Published: November 2019

AbstractDevelopmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor geneNr3c1has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of theNr3c1gene in blood. Having been reared in a large brood induced higher DNA methylation of theNr3c1regulatory region in adulthood, and this effect persisted over years.Nr3c1expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect onNr3c1methylation at our target region.Nr3c1expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of theNr3c1regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.
Ferroelectric switching in ferroelastic materials with rough surfaces
Authors: Lu Guangming , Li Suzhi , Ding Xiangdong , Sun Jun , Salje Ekhard K. H. 
Published: November 2019

AbstractElectric switching of non-polar bulk crystals is shown to occur when domain walls are polar in ferroelastic materials and when rough surfaces with steps on an atomic scale promote domain switching. All domains emerging from surface nuclei possess polar domain walls. The progression of domains is then driven by the interaction of the electric field with the polarity of domain boundaries. In contrast, smooth surfaces with higher activation barriers prohibit effective domain nucleation. We demonstrate the existence of an electrically driven ferroelectric hysteresis loop in a non-ferroelectric, ferroelastic bulk material.