bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulating Climate Change Impacts on Surface Water Resources Within a Lake‐Affected Region Using Regional Climate Projections
Authors: Erler Andre R. , Frey Steven K. , Khader Omar , d'Orgeville Marc , Park Young‐Jin , Hwang Hyoun‐Tae , Lapen David R. , Richard Peltier W. , Sudicky Edward A. 
Published: November 2018

AbstractThis study aims to assess the impact of climate change on water resources in a large watershed within the Laurentian Great Lakes region, using the fully integrated surface‐subsurface model HydroGeoSphere. The hydrologic model is forced with an ensemble of high‐resolution climate projections from the Weather Research and Forecasting (WRF) model. The latter has been extended with an interactive lake model (FLake) to capture the effect of the Great Lakes on the regional climate. The WRF ensemble encompasses two different moist physics configurations at resolutions of 90, 30, and 10 km, as well as four different initial and boundary conditions, so as to control for natural climate variability. The integrated hydrologic model is run with a representative seasonal cycle, which effectively controls natural climate variability, while remaining computationally tractable with a large integrated model. However, the range of natural variability is also investigated, as are the impacts of climate model resolution and bias correction. The two WRF configurations show opposite climate change responses in summer precipitation, but similar responses otherwise. The hydrologic simulations generally follow the climate forcing; however, due to the memory of the subsurface, the differences in summer propagate throughout the entire seasonal cycle. This results in a set of dry scenarios with reduced streamflow and water availability year‐round and a set of wet scenarios with increased streamflow for all times excluding the spring peak, which does not increase. Most of the analysis focuses on streamflow, but changes in the seasonal cycle of baseflow and groundwater recharge are also analyzed.
CBX2 identified as driver of anoikis escape and dissemination in high grade serous ovarian cancer
Authors: Wheeler Lindsay J. , Watson Zachary L. , Qamar Lubna , Yamamoto Tomomi M. , Post Miriam D. , Berning Amber A. , Spillman Monique A. , Behbakht Kian , Bitler Benjamin G. 
Published: November 2018

AbstractHigh grade serous ovarian carcinoma (HGSOC) is often diagnosed at an advanced stage. Chromobox 2 (CBX2), a polycomb repressor complex subunit, plays an oncogenic role in other cancers, but little is known about its role in HGSOC. We hypothesize that CBX2 upregulation promotes HGSOC via induction of a stem-like transcriptional profile and inhibition of anoikis. Examination of Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) established that increased CBX2 expression conveyed chemoresistance and worse disease-free and overall survival. In primary HGSOC tumors, we observed CBX2 expression was significantly elevated compared to benign counterparts. In HGSOC cell lines, forced suspension promoted CBX2 expression. Subsequently, CBX2 knockdown inhibited anchorage-independent proliferation and potentiated anoikis-dependent apoptosis. Furthermore, CBX2 knockdown re-sensitized cells to platinum-based chemotherapy. Forced suspension promoted increased ALDH activity and ALDH3A1 expression and CBX2 knockdown led to a decrease in both ALDH activity and ALDH3A1 expression. Investigation of CBX2 expression on a HGSOC tissue microarray revealed CBX2 expression was apparent in both primary and metastatic tissues. CBX2 is an important regulator of stem-ness, anoikis escape, HGSOC dissemination, and chemoresistance and potentially serves as a novel therapeutic target.
IKKβ activates p53 to promote cancer cell adaptation to glutamine deprivation
Authors: Ishak Gabra Mari B. , Yang Ying , Lowman Xazmin H. , Reid Michael A. , Tran Thai Q. , Kong Mei 
Published: November 2018

AbstractOne of the hallmarks of cancer is the ability to reprogram cellular metabolism to increase the uptake of necessary nutrients such as glucose and glutamine. Driven by oncogenes, cancer cells have increased glutamine uptake to support their highly proliferative nature. However, as cancer cells continue to replicate and grow, they lose access to vascular tissues and deplete local supply of nutrients and oxygen. We previously showed that many tumor cells situate in a low glutamine microenvironment in vivo, yet the mechanisms of how they are able to adapt to this metabolic stress are still not fully understood. Here, we report that IκB-kinase β (IKKβ) is needed to promote survival and its activation is accompanied by phosphorylation of the metabolic sensor, p53, in response to glutamine deprivation. Knockdown of IKKβ decreases the level of wild-type and mutant p53 phosphorylation and its transcriptional activity, indicating a novel relationship between IKKβ and p53 in mediating cancer cell survival in response to glutamine withdrawal. Phosphopeptide mass spectrometry analysis further reveals that IKKβ phosphorylates p53 on Ser392 to facilitate its activation upon glutamine deprivation, independent of the NF-κB pathway. The results of this study offer an insight into the metabolic reprogramming in cancer cells that is dependent on a previously unidentified IKKβ–p53 signaling axis in response to glutamine depletion. More importantly, this study highlights a new therapeutic strategy for cancer treatment and advances our understanding of adaptive mechanisms that could lead to resistance to current glutamine targeting therapies.
Biocatalytic production of adiponitrile and related aliphatic linear α,ω-dinitriles
Authors: Betke Tobias , Maier Manuel , Gruber-Wölfler Heidrun , Gröger Harald 
Published: November 2018

AbstractLinear α,ω-dinitriles are important precursors for the polymer industry. Most prominently, adiponitrile is produced on an annual scale of ca. 1 million tons. However, a drawback of today’s dominating process is the need for large amounts of highly toxic hydrogen cyanide. In this contribution, an alternative approach towards such linear dinitriles is presented based on dehydration of readily available α,ω-dialdoximes at ambient conditions by means of aldoxime dehydratases. In contrast to existing production routes this biocatalytic route enables a highly regio- and chemoselective approach towards dinitriles without the use of hydrogen cyanide or harsh reaction conditions. In addition, a selective synthesis of adiponitrile with substrate loadings of up to 100 g/L and high yields of up to 80% was achieved. Furthermore, a lab scale process on liter scale leading to > 99% conversion at 50 g/L underlines the potential and robustness of this method for technical applicability.
Genome-wide association meta-analysis yields 20 loci associated with gallstone disease
Authors: Ferkingstad Egil , Oddsson Asmundur , Gretarsdottir Solveig , Benonisdottir Stefania , Thorleifsson Gudmar , Deaton Aimee M. , Jonsson Stefan , Stefansson Olafur A. , Norddahl Gudmundur L. , Zink Florian , Arnadottir Gudny A. , Gunnarsson Bjarni , Halldorsson Gisli H. , Helgadottir Anna , Jensson Brynjar O. , Kristjansson Ragnar P. , Sveinbjornsson Gardar , Sverrisson David A. , Masson Gisli , Olafsson Isleifur , Eyjolfsson Gudmundur I. , Sigurdardottir Olof , Holm Hilma , Jonsdottir Ingileif , Olafsson Sigurdur , Steingrimsdottir Thora , Rafnar Thorunn , Bjornsson Einar S. , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Sulem Patrick , Stefansson Kari 
Published: November 2018

AbstractGallstones are responsible for one of the most common diseases in the Western world and are commonly treated with cholecystectomy. We perform a meta-analysis of two genome-wide association studies of gallstone disease in Iceland and the UK, totaling 27,174 cases and 736,838 controls, uncovering 21 novel gallstone-associated variants at 20 loci. Two distinct low frequency missense variants in SLC10A2, encoding the apical sodium-dependent bile acid transporter (ASBT), associate with an increased risk of gallstone disease (Pro290Ser: OR = 1.36 [1.25–1.49], P = 2.1 × 10–12, MAF = 1%; Val98Ile: OR = 1.15 [1.10–1.20], P = 1.8 × 10–10, MAF = 4%). We demonstrate that lower bile acid transport by ASBT is accompanied by greater risk of gallstone disease and highlight the role of the intestinal compartment of the enterohepatic circulation of bile acids in gallstone disease susceptibility. Additionally, two low frequency missense variants in SERPINA1 and HNF4A and 17 common variants represent novel associations with gallstone disease.
Adipocyte OGT governs diet-induced hyperphagia and obesity
Authors: Li Min-Dian , Vera Nicholas B. , Yang Yunfan , Zhang Bichen , Ni Weiming , Ziso-Qejvanaj Enida , Ding Sheng , Zhang Kaisi , Yin Ruonan , Wang Simeng , Zhou Xu , Fang Ethan X. , Xu Tian , Erion Derek M. , Yang Xiaoyong 
Published: November 2018

AbstractPalatable foods (fat and sweet) induce hyperphagia, and facilitate the development of obesity. Whether and how overnutrition increases appetite through the adipose-to-brain axis is unclear. O-linked beta-D-N-acetylglucosamine (O-GlcNAc) transferase (OGT) couples nutrient cues to O-GlcNAcylation of intracellular proteins at serine/threonine residues. Chronic dysregulation of O-GlcNAc signaling contributes to metabolic diseases. Here we show that adipocyte OGT is essential for high fat diet-induced hyperphagia, but is dispensable for baseline food intake. Adipocyte OGT stimulates hyperphagia by transcriptional activation of de novo lipid desaturation and accumulation of N-arachidonyl ethanolamine (AEA), an endogenous appetite-inducing cannabinoid (CB). Pharmacological manipulation of peripheral CB1 signaling regulates hyperphagia in an adipocyte OGT-dependent manner. These findings define adipocyte OGT as a fat sensor that regulates peripheral lipid signals, and uncover an unexpected adipose-to-brain axis to induce hyperphagia and obesity.
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions
Authors: Ishiyama Noboru , Sarpal Ritu , Wood Megan N. , Barrick Samantha K. , Nishikawa Tadateru , Hayashi Hanako , Kobb Anna B. , Flozak Annette S. , Yemelyanov Alex , Fernandez-Gonzalez Rodrigo , Yonemura Shigenobu , Leckband Deborah E. , Gottardi Cara J. , Tepass Ulrich , Ikura Mitsuhiko 
Published: November 2018

Abstractα-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.
Comprehensive correlation analysis for super-resolution dynamic fingerprinting of cellular compartments using the Zeiss Airyscan detector
Authors: Scipioni L. , Lanzanó L. , Diaspro A. , Gratton E. 
Published: November 2018

AbstractThe availability of the Airyscan detector in the Zeiss LSM 880 has made possible the development of a new concept in fluctuation correlation spectroscopy using super-resolution. The Airyscan unit acquires data simultaneously on 32 detectors arranged in a hexagonal array. This detector opens up the possibility to use fluctuation methods based on time correlation at single points or at a number of points simultaneously, as well as methods based on spatial correlation in the area covered by the detector. Given the frame rate of this detector, millions of frames can be acquired in seconds, providing a robust statistical basis for fluctuation data. We apply the comprehensive analysis to the molecular fluctuations of free GFP diffusing in live cells at different subcellular compartments to show that at the nanoscale different cell environments can be distinguished by the comprehensive fluctuation analysis.
Dissymmetry enhancement in enantioselective synthesis of helical polydiacetylene by application of superchiral light
Authors: He Chenlu , Yang Guang , Kuai Yan , Shan Sizhen , Yang Lin , Hu Jingang , Zhang Douguo , Zhang Qijin , Zou Gang 
Published: November 2018

AbstractSuperchiral light, generated by the interference of two counter-propagating circularly polarized light (CPL) with same frequency, opposite handedness and different intensity, exhibits enhanced dissymmetry in its interaction with chiral molecules, and has the potential for ultrasensitive detection and characterization of chiral molecules. It is anticipated that the enhanced optical dissymmetry in superchiral light (SCL) field may be utilized to promote asymmetric photochemical reactions efficiency. Herein we reported SCL impart greater chiral bias to trigger asymmetric photo-polymerization reaction from initially achiral diacetylene (DA) monomer, and the enhanced optical dissymmetry for whole polydiacetylene (PDA) films could be achieved. An explanation based on the chiral transfer and amplification of chiral bias from SCL during the polymerization process has been proposed. Moreover, thus formed chiral PDA films polymerized by SCL exhibited enhanced enantioselective recognition ability, and can serve as a direct visual probe for the discrimination of some specific enantiomers.
Shavenbaby and Yorkie mediate Hippo signaling to protect adult stem cells from apoptosis
Authors: Bohère Jérôme , Mancheno-Ferris Alexandra , Al Hayek Sandy , Zanet Jennifer , Valenti Philippe , Akino Kohsuke , Yamabe Yuya , Inagaki Sachi , Chanut-Delalande Hélène , Plaza Serge , Kageyama Yuji , Osman Dani , Polesello Cédric , Payre François 
Published: November 2018

AbstractTo compensate for accumulating damages and cell death, adult homeostasis (e.g., body fluids and secretion) requires organ regeneration, operated by long-lived stem cells. How stem cells can survive throughout the animal life remains poorly understood. Here we show that the transcription factor Shavenbaby (Svb, OvoL in vertebrates) is expressed in renal/nephric stem cells (RNSCs) of Drosophila and required for their maintenance during adulthood. As recently shown in embryos, Svb function in adult RNSCs further needs a post-translational processing mediated by the Polished rice (Pri) smORF peptides and impairing Svb function leads to RNSC apoptosis. We show that Svb interacts both genetically and physically with Yorkie (YAP/TAZ in vertebrates), a nuclear effector of the Hippo pathway, to activate the expression of the inhibitor of apoptosis DIAP1. These data therefore identify Svb as a nuclear effector in the Hippo pathway, critical for the survival of adult somatic stem cells.
Unravelling the role of vacancies in lead halide perovskite through electrical switching of photoluminescence
Authors: Li Cheng , Guerrero Antonio , Huettner Sven , Bisquert Juan 
Published: November 2018

AbstractWe address the behavior in which a bias voltage can be used to switch on and off the photoluminescence of a planar film of methylammonium lead triiodide perovskite (MAPbI3) semiconductor with lateral symmetric electrodes. It is observed that a dark region advances from the positive electrode at a slow velocity of order of 10 μm s–1. Here we explain the existence of the sharp front by a drift of ionic vacancies limited by local saturation, that induce defects and drastically reduce the radiative recombination rate in the film. The model accounts for the time dependence of electrical current due to the ion-induced doping modification, that changes local electron and hole concentration with the drift of vacancies. The analysis of current dependence on time leads to a direct determination of the diffusion coefficient of iodine vacancies and provides detailed information of ionic effects over the electrooptical properties of hybrid perovskite materials.
Cardiac specific PRMT1 ablation causes heart failure through CaMKII dysregulation
Authors: Pyun Jung-Hoon , Kim Hyun-Ji , Jeong Myong-Ho , Ahn Byeong-Yun , Vuong Tuan Anh , Lee Dong I. , Choi Seri , Koo Seung-Hoi , Cho Hana , Kang Jong-Sun 
Published: November 2018

AbstractDysregulation of Ca2+/calmodulin-dependent protein kinase (CaMK)II is closely linked with myocardial hypertrophy and heart failure. However, the mechanisms that regulate CaMKII activity are incompletely understood. Here we show that protein arginine methyltransferase 1 (PRMT1) is essential for preventing cardiac CaMKII hyperactivation. Mice null for cardiac PRMT1 exhibit a rapid progression to dilated cardiomyopathy and heart failure within 2 months, accompanied by cardiomyocyte hypertrophy and fibrosis. Consistently, PRMT1 is downregulated in heart failure patients. PRMT1 depletion in isolated cardiomyocytes evokes hypertrophic responses with elevated remodeling gene expression, while PRMT1 overexpression protects against pathological responses to neurohormones. The level of active CaMKII is significantly elevated in PRMT1-deficient hearts or cardiomyocytes. PRMT1 interacts with and methylates CaMKII at arginine residues 9 and 275, leading to its inhibition. Accordingly, pharmacological inhibition of CaMKII restores contractile function in PRMT1-deficient mice. Thus, our data suggest that PRMT1 is a critical regulator of CaMKII to maintain cardiac function.
Loss of peroxiredoxin-2 exacerbates eccentric contraction-induced force loss in dystrophin-deficient muscle
Authors: Olthoff John T. , Lindsay Angus , Abo-Zahrah Reem , Baltgalvis Kristen A. , Patrinostro Xiaobai , Belanto Joseph J. , Yu Dae-Yeul , Perrin Benjamin J. , Garry Daniel J. , Rodney George G. , Lowe Dawn A. , Ervasti James M. 
Published: November 2018

AbstractForce loss in skeletal muscle exposed to eccentric contraction is often attributed to injury. We show that EDL muscles from dystrophin-deficient mdx mice recover 65% of lost force within 120 min of eccentric contraction and exhibit minimal force loss when the interval between contractions is increased from 3 to 30 min. A proteomic screen of mdx muscle identified an 80% reduction in the antioxidant peroxiredoxin-2, likely due to proteolytic degradation following hyperoxidation by NADPH Oxidase 2. Eccentric contraction-induced force loss in mdx muscle was exacerbated by peroxiredoxin-2 ablation, and improved by peroxiredoxin-2 overexpression or myoglobin knockout. Finally, overexpression of γcyto- or βcyto-actin protects mdx muscle from eccentric contraction-induced force loss by blocking NADPH Oxidase 2 through a mechanism dependent on cysteine 272 unique to cytoplasmic actins. Our data suggest that eccentric contraction-induced force loss may function as an adaptive circuit breaker that protects mdx muscle from injurious contractions.
High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries
Authors: Jain Chirag , Rodriguez-R Luis M. , Phillippy Adam M. , Konstantinidis Konstantinos T. , Aluru Srinivas 
Published: November 2018

AbstractA fundamental question in microbiology is whether there is continuum of genetic diversity among genomes, or clear species boundaries prevail instead. Whole-genome similarity metrics such as Average Nucleotide Identity (ANI) help address this question by facilitating high resolution taxonomic analysis of thousands of genomes from diverse phylogenetic lineages. To scale to available genomes and beyond, we present FastANI, a new method to estimate ANI using alignment-free approximate sequence mapping. FastANI is accurate for both finished and draft genomes, and is up to three orders of magnitude faster compared to alignment-based approaches. We leverage FastANI to compute pairwise ANI values among all prokaryotic genomes available in the NCBI database. Our results reveal clear genetic discontinuity, with 99.8% of the total 8 billion genome pairs analyzed conforming to >95% intra-species and <83% inter-species ANI values. This discontinuity is manifested with or without the most frequently sequenced species, and is robust to historic additions in the genome databases.
A fully inkjet-printed disposable glucose sensor on paper
Authors: Bihar Eloïse , Wustoni Shofarul , Pappa Anna Maria , Salama Khaled N. , Baran Derya , Inal Sahika 
Published: November 2018

AbstractInexpensive and easy-to-use diagnostic tools for fast health screening are imperative, especially in the developing world, where portability and affordability are a necessity. Accurate monitoring of metabolite levels can provide useful information regarding key metabolic activities of the body and detect the concomitant irregularities such as in the case of diabetes, a worldwide chronic disease. Today, the majority of daily glucose monitoring tools rely on piercing the skin to draw blood. The pain and discomfort associated with finger pricking have created a global need to develop non-invasive, portable glucose assays. In this work, we develop a disposable analytical device which can measure physiologically relevant glucose concentrations in human saliva based on enzymatic electrochemical detection. We use inkjet-printing technology for the rapid and low-cost deposition of all the components of this glucose sensor, from the electronics to the biorecognition elements, on commercially available paper substrates. The only electronic component of the sensor is the conducting polymer poly(3,4 ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS), while the biorecognition element comprises of the enzyme glucose oxidase coupled with an electron mediator. We demonstrate that one month after its fabrication and storage in air-free environment, the sensor maintains its function with only minor performance loss. This fully printed, all-polymer biosensor with its ease of fabrication, accuracy, sensitivity and compatibility with easy-to-obtain biofluids such as saliva aids in the development of next generation low-cost, non-invasive, eco-friendly, and disposable diagnostic tools.
Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial–mesenchymal transition suppression and cell polarity disruption
Authors: Lee Cheng-Che , Cheng Yun-Ching , Chang Chi-Yen , Lin Chi-Min , Chang Jang-Yang 
Published: November 2018

AbstractMEC-17, a newly identified alpha-tubulin-N-acetyltransferase 1, serves as the major α-tubulin acetyltransferase to promote α-tubulin acetylation in vitro and in vivo. Alteration of α-tubulin acetylation may be involved in morphology regulation, cell migration, and tumour metastasis. However, MEC-17’s role in cell physiology and its effect on epithelial–mesenchymal transition (EMT) and cell polarity remain elusive. In the present study, we characterized the overexpressed or downregulated cell models through gene targeting as MEC-17 gain- or loss-of-function. Overexpression of MEC-17 enhanced the cell spreading area, suppressed pseudopods formation in a three-dimensional (3D) culture system, and inhibited cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Furthermore, morphological change and migration inhibition of cancer cells were accompanied by EMT repression, Golgi reorientation, and polarity disruption caused by alteration of cdc42 activity via a decrease in Rho-GAP, ARHGAP21. By contrast, a reduction in endogenous MEC-17 accelerated the pseudopods formation and EMT, and facilitated cell migration and invasion. These results demonstrated the crucial role of MEC-17 in the modulation of intrinsic cell morphogenesis, migration, and invasive function through regulation of EMT and cell polarity.