bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Determinants of Telomere Length in African American Youth
Authors: Zeiger Andrew M. , White Marquitta J. , Eng Celeste , Oh Sam S. , Witonsky Jonathan , Goddard Pagé C. , Contreras Maria G. , Elhawary Jennifer R. , Hu Donglei , Mak Angel C. Y. , Lee Eunice Y. , Keys Kevin L. , Samedy Lesly-Anne , Risse-Adams Oona , Magaña Joaquín , Huntsman Scott , Salazar Sandra , Davis Adam , Meade Kelley , Brigino-Buenaventura Emerita , LeNoir Michael A. , Farber Harold J. , Bibbins-Domingo Kirsten , Borrell Luisa N. , Burchard Esteban G. 
Published: August 2018

AbstractTelomere length (TL) is associated with numerous disease states and is affected by genetic and environmental factors. However, TL has been mostly studied in adult populations of European or Asian ancestry. These studies have identified 34 TL-associated genetic variants recently used as genetic proxies for TL. The generalizability of these associations to pediatric populations and racially diverse populations, specifically of African ancestry, remains unclear. Furthermore, six novel variants associated with TL in a population of European children have been identified but not validated. We measured TL from whole blood samples of 492 healthy African American youth (children and adolescents between 8 and 20 years old) and performed the first genome-wide association study of TL in this population. We were unable to replicate neither the 34 reported genetic associations found in adults nor the six genetic associations found in European children. However, we discovered a novel genome-wide significant association between TL and rs1483898 on chromosome 14. Our results underscore the importance of examining genetic associations with TL in diverse pediatric populations such as African Americans.
Lysyl oxidase (LOX) limits VSMC proliferation and neointimal thickening through its extracellular enzymatic activity
Authors: Varona Saray , Orriols Mar , Galán María , Guadall Anna , Cañes Laia , Aguiló Silvia , Sirvent Marc , Martínez-González José , Rodríguez Cristina 
Published: August 2018

AbstractLysyl oxidase (LOX) plays a critical role in extracellular matrix maturation and limits VSMC proliferation and vascular remodeling. We have investigated whether this anti-proliferative effect relies on the extracellular catalytically active LOX or on its biologically active propeptide (LOX-PP). High expression levels of both LOX and LOX-PP were detected in the vascular wall from transgenic mice over-expressing the full-length human LOX cDNA under the control of SM22α promoter (TgLOX), which targets the transgene to VSMC without affecting the expression of mouse LOX isoenzymes. TgLOX VSMC also secrete high amounts of both mature LOX and LOX-PP. Wild-type (WT) mouse VSMC exposed to VSMC supernatants from transgenic animals showed reduced proliferative rates (low [3H]-thymidine uptake and expression of PCNA) than those incubated with conditioned media from WT cells, effect that was abrogated by β-aminopropionitrile (BAPN), an inhibitor of LOX activity. Lentiviral over-expression of LOX, but not LOX-PP, decreased human VSMC proliferation, effect that was also prevented by BAPN. LOX transgenesis neither impacted local nor systemic inflammatory response induced by carotid artery ligation. Interestingly, in this model, BAPN normalized the reduced neointimal thickening observed in TgLOX mice. Therefore, extracellular enzymatically active LOX is required to limit both VSMC proliferation and vascular remodeling.
In Vitro Selection of Specific DNA Aptamers Against the Anti-Coagulant Dabigatran Etexilate
Authors: Aljohani Maher M. , Chinnappan Raja , Eissa Shimaa , Alsager Omar A. , Weber Karina , Cialla-May Dana , Popp Jürgen , Zourob Mohammed 
Published: August 2018

AbstractDabigatran Etexilate (PRADAXA) is a new oral anticoagulant increasingly used for a number of blood thrombosis conditions, prevention of strokes and systemic emboli among patients with atrial fibrillation. It provides safe and adequate anticoagulation for prevention and treatment of thrombus in several clinical settings. However, anticoagulation therapy can be associated with an increased risk of bleeding. There is a lack of specific laboratory tests to determine the level of this drug in blood. This is considered the most important obstacles of using this medication, particularly for patients with trauma, drug toxicity, in urgent need for surgical interventions or uncontrolled bleeding. In this work, we performed Systematic evolution of ligands by exponential enrichment (SELEX) to select specific DNA aptamers against dabigatran etexilate. Following multiple rounds of selection and enrichment with a randomized 60-mer DNA library, specific DNA aptamers for dabigatran were selected. We investigated the affinity and specificity of generated aptamers to the drug showing dissociation constants (Kd) ranging from 46.8–208 nM. The most sensitive aptamer sequence was selected and applied in an electrochemical biosensor to successfully achieve 0. 01 ng/ml level of detection of the target drug. With further improvement of the assay and optimization, these aptamers would replace conventional antibodies for developing detection assays in the near future.
Indirect Reciprocity and the Evolution of Prejudicial Groups
Authors: Whitaker Roger M. , Colombo Gualtiero B. , Rand David G. 
Published: August 2018

AbstractPrejudicial attitudes are widely seen between human groups, with significant consequences. Actions taken in light of prejudice result in discrimination, and can contribute to societal division and hostile behaviours. We define a new class of group, the prejudicial group, with membership based on a common prejudicial attitude towards the out-group. It is assumed that prejudice acts as a phenotypic tag, enabling groups to form and identify themselves on this basis. Using computational simulation, we study the evolution of prejudicial groups, where members interact through indirect reciprocity. We observe how cooperation and prejudice coevolve, with cooperation being directed in-group. We also consider the co-evolution of these variables when out-group interaction and global learning are immutable, emulating the possible pluralism of a society. Diversity through three factors is found to be influential, namely out-group interaction, out-group learning and number of sub-populations. Additionally populations with greater in-group interaction promote both cooperation and prejudice, while global rather than local learning promotes cooperation and reduces prejudice. The results also demonstrate that prejudice is not dependent on sophisticated human cognition and is easily manifested in simple agents with limited intelligence, having potential implications for future autonomous systems and human-machine interaction.
Changes in benthic community structure and sediment characteristics after natural recolonisation of the seagrass Zostera muelleri
Authors: Lundquist Carolyn J. , Jones Tracey C. , Parkes Samantha M. , Bulmer Richard H. 
Published: August 2018

AbstractMacrofauna are important contributors to estuarine ecosystem services within and outside of seagrass beds. Here we documented the natural recolonisation of a temperate seagrass (Zostera muelleri) community over 15 years in an urban estuary (Waitemata Harbour, North Island, New Zealand). We also investigated the change in macrofaunal communities in relation to seagrass cover over time, from transition from bare sandflat to seagrass. Colonisation by seagrass was associated with an increase in macrofaunal species diversity (from an average of 32 species per core in 2001 to 46 species per core in 2015) and abundance (from 482 to 2273 individuals per core), as well as an increase in sediment mud (from 4.09% to 12.37%) and organic matter content (from 0.90% to 1.41%). The most abundant species within both seagrass and adjacent unvegetated sandflat were similar, the polychaetes Heteromastus filiformis, Aricidea sp., and Prionospio aucklandica, and the amphipod Paracalliope novizealandiae. The difference in macrofaunal community structure between seagrass and unvegetated sandflat was primarily associated with higher abundance of P. novizealandiae and lower abundance of Pseudopolydora sp. in seagrass. A successional effect was observed in macrofaunal communities over the 15 years following seagrass expansion, primarily associated with an increase in the abundance of Aricidea sp., H. filiformis, and P. novizealandiae, and a reduction in the abundance of the bivalve Linucula hartvigiana. This study is the first to document long-term changes in seagrass and their associated communities during a natural recolonisation event, providing insight into timeframes required both for the regrowth of a seagrass meadow from initial colonisation of individual patches, as well as the trajectories and timeframes of change from a sandflat to a seagrass-associated macrofaunal community. This research enhances our understanding of how changes in seagrass distributions due to seagrass loss or restoration may affect macrofaunal community composition and ultimately ecosystem function.
Impact of energy dissipation on interface shapes and on rates for dewetting from liquid substrates
Authors: Peschka Dirk , Bommer Stefan , Jachalski Sebastian , Seemann Ralf , Wagner Barbara 
Published: August 2018

AbstractWe revisit the fundamental problem of liquid-liquid dewetting and perform a detailed comparison of theoretical predictions based on thin-film models with experimental measurements obtained by atomic force microscopy. Specifically, we consider the dewetting of a liquid polystyrene layer from a liquid polymethyl methacrylate layer, where the thicknesses and the viscosities of both layers are similar. Using experimentally determined system parameters like viscosity and surface tension, an excellent agreement of experimentally and theoretically obtained rim profile shapes are obtained including the liquid-liquid interface and even dewetting rates. Our new energetic approach additionally allows to assess the physical importance of different contributions to the energy-dissipation mechanism, for which we analyze the local flow fields and the local dissipation rates. Using this approach, we explain why dewetting rates for liquid-liquid systems follow no universal power law, despite the fact that experimental velocities are almost constant. This is in contrast to dewetting scenarios on solid substrates and in contrast to previous results for liquid-liquid substrates using heuristic approaches.
Impact of cyber-invasive species on a large ecological network
Authors: Doizy Anna , Barter Edmund , Memmott Jane , Varnham Karen , Gross Thilo 
Published: August 2018

AbstractAs impacts of introduced species cascade through trophic levels, they can cause indirect and counter-intuitive effects. To investigate the impact of invasive species at the network scale, we use a generalized food web model, capable of propagating changes through networks with a series of ecologically realistic criteria. Using data from a small British offshore island, we quantify the impacts of four virtual invasive species (an insectivore, a herbivore, a carnivore and an omnivore whose diet is based on a rat) and explore which clusters of species react in similar ways. We find that the predictions for the impacts of invasive species are ecologically plausible, even in large networks. Species in the same taxonomic group are similarly impacted by a virtual invasive species. However, interesting differences within a given taxonomic group can occur. The results suggest that some native species may be at risk from a wider range of invasives than previously believed. The implications of these results for ecologists and land managers are discussed.
E-hooks provide guidance and a soft landing for the microtubule binding domain of dynein
Authors: Tajielyato Nayere , Li Lin , Peng Yunhui , Alper Joshua , Alexov Emil 
Published: August 2018

AbstractMacromolecular binding is a complex process that involves sensing and approaching the binding partner, adopting the proper orientation, and performing the physical binding. We computationally investigated the role of E-hooks, which are intrinsically disordered regions (IDRs) at the C-terminus of tubulin, on dynein microtubule binding domain (MTBD) binding to the microtubule as a function of the distance between the MTBD and its binding site on the microtubule. Our results demonstrated that the contacts between E-hooks and the MTBD are dynamical; multiple negatively charted patches of amino acids on the E-hooks grab and release the same positively charged patches on the MTBD as it approaches the microtubule. Even when the distance between the MTBD and the microtubule was greater than the E-hook length, the E-hooks sensed and guided MTBD via long-range electrostatic interactions in our simulations. Moreover, we found that E-hooks exerted electrostatic forces on the MTBD that were distance dependent; the force pulls the MTBD toward the microtubule at long distances but opposes binding at short distances. This mechanism provides a “soft-landing” for the MTBD as it binds to the microtubule. Finally, our analysis of the conformational states of E-hooks in presence and absence of the MTBD indicates that the binding process is a mixture of the induced-fit and lock-and-key macromolecular binding hypotheses. Overall, this novel binding mechanism is termed “guided-soft-binding” and could have broad-reaching impacts on the understanding of how IDRs dock to structured proteins.
Operation Mechanism of GaN-based Transistors Elucidated by Element-Specific X-ray Nanospectroscopy
Authors: Omika Keiichi , Tateno Yasunori , Kouchi Tsuyoshi , Komatani Tsutomu , Yaegassi Seiji , Yui Keiichi , Nakata Ken , Nagamura Naoka , Kotsugi Masato , Horiba Koji , Oshima Masaharu , Suemitsu Maki , Fukidome Hirokazu 
Published: August 2018

AbstractWith the rapid depletion of communication-frequency resources, mainly due to the explosive spread of information communication devices for the internet of things, GaN-based high-frequency high-power transistors (GaN-HEMTs) have attracted considerable interest as one of the key devices that can operate in the high-frequency millimeter-wave band. However, GaN-HEMT operation is destabilized by current collapse phenomena arising from surface electron trapping (SET), which has not been fully understood thus far. Here, we conduct quantitative mechanistic studies on SET in GaN-HEMTs by applying element- and site-specific photoelectron nanospectroscopy to a GaN-HEMT device under operation. Our study reveals that SET is induced by a large local electric field. Furthermore, surface passivation using a SiN thin film is demonstrated to play a dual role: electric-field weakening and giving rise to chemical interactions that suppress SET. Our findings can contribute to the realization of high-capacity wireless communication systems based on GaN-HEMTs.
Dynamics of neural representations when searching for exemplars and categories of human and non-human faces
Authors: Bayet Laurie , Zinszer Benjamin , Pruitt Zoe , Aslin Richard N. , Wu Rachel 
Published: August 2018

AbstractFace perception abilities in humans exhibit a marked expertise in distinguishing individual human faces at the expense of individual faces from other species (the other-species effect). In particular, one behavioural effect of such specialization is that human adults search for and find categories of non-human faces faster and more accurately than a specific non-human face, and vice versa for human faces. However, a recent visual search study showed that neural responses (event-related potentials, ERPs) were identical when finding either a non-human or human face. We used time-resolved multivariate pattern analysis of the EEG data from that study to investigate the dynamics of neural representations during a visual search for own-species (human) or other-species (non-human ape) faces, with greater sensitivity than traditional ERP analyses. The location of each target (i.e., right or left) could be decoded from the EEG, with similar accuracy for human and non-human faces. However, the neural patterns associated with searching for an exemplar versus a category target differed for human faces compared to non-human faces: Exemplar representations could be more reliably distinguished from category representations for human than non-human faces. These findings suggest that the other-species effect modulates the nature of representations, but preserves the attentional selection of target items based on these representations.
Detection of high-risk carbapenem-resistant Klebsiella pneumoniae and Enterobacter cloacae isolates using volatile molecular profiles
Authors: Rees Christiaan A. , Nasir Mavra , Smolinska Agnieszka , Lewis Alexa E. , Kane Katherine R. , Kossmann Shannon E. , Sezer Orkan , Zucchi Paola C. , Doi Yohei , Hirsch Elizabeth B. , Hill Jane E. 
Published: August 2018

AbstractInfections caused by carbapenem-resistantEnterobacteriaceae(CRE) are alarming in the clinical setting, as CRE isolates often exhibit resistance to most clinically-available antibiotics.Klebsiella pneumoniaecarbapenemase (KPC) is the most common carbapenemase carried by CRE in North America and Europe, frequently detected in isolates ofK.pneumoniae,Escherichia coli, andEnterobacter cloacae. Notably, KPC-expressing strains often arise from clonal lineages, with sequence type 258 (ST258) representing the dominant lineage inK.pneumoniae, ST131 inE.coli, and ST78 and ST171 inE.cloacae. Prior studies have demonstrated that carbapenem-resistantK.pneumoniaediffers from carbapenem-susceptibleK.pneumoniaeat both the transcriptomic and soluble metabolomic levels. In the present study, we sought to determine whether carbapenem-resistant and carbapenem-susceptible isolates ofK.pneumoniae,E.coli, andE.cloacaeproduce distinct volatile metabolic profiles. We were able to identify a volatile metabolic fingerprint that could discriminate between CRE and non-CRE with an area under the receiver operating characteristic curve (AUROC) as high as 0.912. Species-specific AUROCs were as high as 0.988 forK.pneumoniaeand 1.000 forE.cloacae. Paradoxically, curing of KPC-expressing plasmids from a subset ofK.pneumoniaeisolates further accentuated the metabolic differences observed between ST258 and non-ST258.
Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma
Authors: Wang Guanghui , Bie Fenglong , Qu Xiao , Yang Xudong , Liu Shaorui , Wang Yu , Huang Cuicui , Wang Kai , Du Jiajun 
Published: August 2018

AbstractLiver kinase B1 (LKB1) is a tumor suppressor, and there is a very high proportion of LKB1 mutation in lung adenocarcinoma. The function of LKB1 is closely related to that of ubiquitin related genes. Our objective is to analyze the changes in ubiquitin-related genes in LKB1 mutant lung adenocarcinoma. We searched The Cancer Genome Atlas (TCGA) and obtained gene expression profiles from 230 lung adenocarcinoma patients, which were then analyzed using R software. Kaplan–Meier curves and Cox proportional hazards regression were applied to estimate survival. Real-time reverse transcription PCR was used to verify gene expression. Gene function was explored by gene set enrichment analysis. There were significantly expressed differences in the ubiquitin-related gene SH3RF1 between the LKB1 mutant and wild-type lung adenocarcinoma patients (p = 9.78013E-05). Patients with LKB1 mutation and high expression of SH3RF1 had a better prognosis than the low expression group (HR 0.356, 95% CI 0.136–0.929, p = 0.035). SH3RF1 can influence cell cycle, apoptosis, DNA replication and the p53 signaling pathway. SH3RF1 might have great clinical value act as a diagnostic biomarker and indicator to evaluate the prognosis of LKB1 mutant lung adenocarcinoma patients. This gene also can become a new treatment target for LKB1 mutant lung adenocarcinoma patients.
Small-scale displacement fluctuations of vesicles in fibroblasts
Authors: Posey Danielle , Blaisdell-Pijuan Paris , Knoll Samantha K. , Saif Taher A. , Ahmed Wylie W. 
Published: August 2018

AbstractThe intracellular environment is a dynamic space filled with various organelles moving in all directions. Included in this diverse group of organelles are vesicles, which are involved in transport of molecular cargo throughout the cell. Vesicles move in either a directed or non-directed fashion, often depending on interactions with cytoskeletal proteins such as microtubules, actin filaments, and molecular motors. How these proteins affect the local fluctuations of vesicles in the cytoplasm is not clear since they have the potential to both facilitate and impede movement. Here we show that vesicle mobility is significantly affected by myosin-II, even though it is not a cargo transport motor. We find that myosin-II activity increases the effective diffusivity of vesicles and its inhibition facilitates longer states of non-directed motion. Our study suggests that altering myosin-II activity in the cytoplasm of cells can modulate the mobility of vesicles, providing a possible mechanism for cells to dynamically tune the cytoplasmic environment in space and time.
Interplay between interferon regulatory factor 1 and BRD4 in the regulation of PD-L1 in pancreatic stellate cells
Authors: Ebine Kazumi , Kumar Krishan , Pham Thao N. , Shields Mario A. , Collier Katharine A. , Shang Meng , DeCant Brian T. , Urrutia Raul , Hwang Rosa F. , Grimaldo Sam , Principe Daniel R. , Grippo Paul J. , Bentrem David J. , Munshi Hidayatullah G. 
Published: August 2018

AbstractThe fibrotic reaction is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of fibrosis in vivo. While there is increasing interest in the regulation of PD-L1 expression in cancer and immune cells, the expression and regulation of PD-L1 in other stromal cells, such as PSCs, has not been fully evaluated. Here we show that PSCs in vitro express higher PD-L1 mRNA and protein levels compared to the levels present in PDAC cells. We show that inhibitors targeting bromodomain and extra-terminal (BET) proteins and BRD4 knockdown decrease interferon-γ (IFN-γ)-induced PD-L1 expression in PSCs. We also show that c-MYC, one of the well-established targets of BET inhibitors, does not mediate IFN-γ-regulated PD-L1 expression in PSCs. Instead we show that interferon regulatory factor 1 (IRF1) mediates IFN-γ-induced PD-L1 expression in PSCs. Finally, while we show that BET inhibitors do not regulate IFN-γ-induced IRF1 expression in PSCs, BET inhibitors decrease binding of IRF1 and BRD4 to the PD-L1 promoter. Together, these results demonstrate the interplay between IRF1 and BRD4 in the regulation of PD-L1 in PSCs.