bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modes of Propagation of Continental Breakup and Associated Oblique Rift Structures
Authors: Jourdon Anthony , Le Pourhiet Laetitia , Mouthereau Frédéric , May Dave 
Published: August 2020

AbstractV‐shaped oceanic propagators are widespread around the world. Their geometry combined with magnetic anomalies associated with their opening shows at the first order that ridge propagation in the third dimension occurs by pulses. In this study we use 3D thermomechanical numerical models to show how oblique kinematic boundary conditions control both the intracontinental rift development and the oceanic ridge propagation. To do so, we apply a shortening velocity boundary condition in the direction perpendicular to the extension for “strong” and “weak” crustal rheologies. Numerical model results highlight the finding that three ridge propagation modes can occur. For low out‐of‐plane velocities (12% to 15% of the extension rate), the ridge propagation is fast (>1.5 cm year−1) and straight. Higher shortening velocities (15% to 17%) lead to a ridge propagation by pulses alternating between fast propagation (~1.5 cm year−1) and stalling phases. Finally, for higher velocities (17% to 20%) a ridge jump propagation mode occurs, localizing a new spreading center between 100 and 200 km far from the initial ridge. We also show that ridge propagation phases are associated with dip‐slip‐dominated deformation, while stalling phases are dominated by strike‐slip deformation. These deformation regimes are marked by structure reorientation, while kinematic boundary conditions remain constant. We discuss these results in terms of plate tectonic reconstructions and regional geological studies.
Thermal Pressure in the Laser‐Heated Diamond Anvil Cell: A Quantitative Study and Implications for the Density Versus Mineralogy Correlation of the Mantle
Authors: Yen Connor Ethan , Williams Quentin , Kunz Martin 
Published: August 2020

AbstractThermal pressure is an inevitable thermodynamic consequence of heating a volumetrically constrained sample in the diamond anvil cell. Its possible influences on experimentally determined density‐mineralogy correlations are widely appreciated, yet the effect itself has never been experimentally measured. We present here the first quantitative measurements of the spatial distribution of thermal pressure in a laser‐heated diamond anvil cell (LHDAC) in both olivine and AgI. The observed thermal pressure is strongly localized and closely follows the distribution of the laser hotspot. The magnitude of the thermal pressure is of the order of the thermodynamic thermal pressure (αKTΔT) with gradients between 0.5 and 1.0 GPa/10 μm. Remarkably, we measure a steep gradient in thermal pressure even in a sample that is heated close to its melting line. This generates consequences for pressure determinations in pressure‐volume‐temperature (PVT) equation of state measurements when using an LHDAC. We show that an incomplete account of thermal pressure in PVT experiments can lead to biases in the coveted depth versus mineralogy correlation. However, the ability to spatially resolve thermal pressure in an LHDAC opens avenues to measure difficult‐to‐constrain thermodynamic derivative properties, which are important for comprehensive thermodynamic descriptions of the interior of planets.
Summer High‐Wind Events and Phytoplankton Productivity in the Arctic Ocean
Authors: Crawford Alex D. , Krumhardt Kristen M. , Lovenduski Nicole S. , van Dijken Gert L. , Arrigo Kevin R. 
Published: August 2020

AbstractAt the base of the marine food web, phytoplankton are an essential component of the Arctic Ocean ecosystem and carbon cycle. Especially after sea ice retreats and light becomes more available to the Arctic Ocean each summer, phytoplankton productivity is limited by nutrient availability, which can be replenished by vertical mixing of the water column. One potential mixing mechanism is gale‐force wind associated with summer storm activity. Past studies show that sustained high winds (>10 m s−1) impart sufficient stress on the ocean surface to induce vertical mixing, and it has been speculated that greater storm activity may increase net primary productivity (NPP) on a year‐to‐year timescale. We test this idea using a combination of satellite products and reanalysis data from 1998 to 2018. After controlling for the amount of open water, sea‐surface temperature, and wind direction, we find evidence that greater frequency of high‐wind events in summer is associated with greater seasonal NPP in the Barents, Laptev, East Siberian, and southern Chukchi Seas. This relationship is only robust for the Barents and southern Chukchi Seas, which are more strongly impacted by inflow of relatively nutrient‐rich water from the Atlantic and Pacific Oceans, respectively. In other words, stormier summers may have higher productivity in several regions of the Arctic Ocean, but especially the two inflow seas. Additionally, a recent rise in high‐wind frequency in the Barents Sea may have contributed to the simultaneous increase in NPP.
Linking Geomorphic Process Dominance and the Persistence of Local Elevation
Authors: Sweeney Kristin E. , Roering Joshua J. , Furbish David J. 
Published: August 2020

AbstractThe response of eroding topography to changes in base level is driven by patchy and intermittent mass flux, both on hillslopes and in channels. However, most models of soil‐mantled landscape evolution use continuously differentiable equations that average over these patchy transport processes. Because of the limited time and space resolution of field observations, the relationship between zeroth‐order landscape evolution (i.e., over long space and time scales) and first‐order fluctuations due to patchy, intermittent transport (e.g., tree throw and landsliding) remains unclear. Here, we use five physical experiments of an eroding experimental landscape to examine how the signature of first‐order transport, as described by autocorrelation functions of local elevation time series, varies as a function of the vigor of hillslope transport relative to channel incision. Our results show that experiments with higher hillslope transport efficacy have higher autocorrelation coefficients, suggesting that differences in zeroth‐order transport coefficients may be driven by differences in patchy, first‐order transport processes. These higher autocorrelation coefficients also imply that in landscapes where hillslope transport dominates, landscape dynamism is reduced and patterns of elevation change are more persistent over time. These findings suggest that the balance between channelized and hillslope transport processes is fundamental to landscape response to perturbation and may control landscape susceptibility to unsteady processes like large‐scale reorganization.
Transient Groundwater Flow Through a Coastal Confined Aquifer and Its Impact on Nearshore Submarine Slope Instability
Authors: Sultan N. , Garziglia S. , Bompais X. , Woerther P. , Witt C. , Kopf A. , Migeon S. 
Published: August 2020

AbstractRare in situ pore pressure and temperature data sets collected over more than one decade in a submarine landslide‐prone area off Nice (Southeast France) have been used to characterize a transient groundwater exchange between a coastal confined aquifer and the nearshore shallow‐water submarine shelf. The near‐coast study zone is highly exposed to geohazards and remains sadly famous for the 1979 catastrophic tsunamigenic submarine landslide with several casualties and substantial material damage. Measured pore pressure buildup does not appear to be synchronized with either the discharge of the nearby Var River or with precipitation in the Nice area. Unexpectedly, pore pressure fluctuations synchronizes well with seabed temperature trends indicating that the nearshore submarine shelf is mainly impacted by long smooth seasonal variations. We used the pore pressure and temperature data to describe the general transport mechanisms of pore waters and show that pore pressure diffusion is predominantly responsible for the near‐seabed pore pressure buildup. Based on our results and previously published geotechnical data, slope stability calculations reveal that groundwater exchange has a major impact on slope instability and shear zone formation in a prone‐to‐failure area. Minor earthquake‐induced ground accelerations seem to contribute to the nearshore slope instability by decreasing its factor of safety.
Vertical Structure of Ocean Mesoscale Eddies with Implications for Parameterizations of Tracer Transport
Authors: Stanley Z. , Bachman S. D. , Grooms I. 
Published: August 2020

AbstractThe Gent–McWilliams parameterization is commonly used in global ocean models to model the advective component of tracer transport effected by unresolved mesoscale eddies. The vertical structure of the transfer coefficient in this parameterization is studied using data from a 0.1° resolution global ocean‐ice simulation. The vertical structure is found to be well approximated by a baroclinic mode structure with no flow at the bottom, though horizontal anisotropy is crucial for obtaining a good fit. This vertical structure is motivated by reference to the vertical structure of mesoscale eddy velocity and density anomalies, which are also diagnosed from the data.
Exhumation Timing in the Oregon Cascade Range Decoupled From Deformation, Magmatic, and Climate Patterns
Authors: Pesek Maria E. , Perez Nicholas D. , Meigs Andrew , Rowden C. Charles , Giles Sarah M. 
Published: August 2020

AbstractThe Cascade Range in the Pacific Northwest, USA, developed as an Eocene to recent volcanic arc along the Pacific/North American ocean‐continent subduction zone. The volcanic arc is characterized by temporally and spatially variable magmatism. Crustal deformation that accompanied development of the arc transitions from N‐S transpression in the Yakima Fold Belt and Puget lowland (western Washington, northern Oregon) to generally E‐W transtension in the south (central and southern Oregon). Orography focuses precipitation along the western flank of the Cascade Range, whereas the eastern flank is relatively arid. We use the unique spatial variation in deformation, magmatic history, and orographic precipitation to investigate the contributions from tectonic and surface processes to rock uplift. We reconstruct the exhumation pathway of plutonic rocks throughout the Cascade Range by exploiting the unique juxtaposition of basalt‐capped ridges above valleys exposing exhumed Cenozoic plutons. Multiple bedrock geochronometers and thermochronometers constrain the thermal history in six catchments along the Cascade arc from southern Oregon to southern Washington. U‐Pb geochronology defines circa 10–24 Ma pluton crystallization ages. Apatite and zircon (U‐Th)/He thermochronology ages range from circa 8–23 Ma. 40Ar/39Ar geochronology defines circa 5–8 Ma basalt emplacement. Our results reveal spatially and temporally variable shallow exhumation in the southern Washington and Oregon Cascades and that the timing of exhumation is earlier than circa 6–12 Ma exhumation previously reported in the Washington Cascades. Spatially and temporally variable exhumation highlights that crustal deformation plays a significant role in rock uplift in addition to erosional mass removal in concert with orographic precipitation.
Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease
Authors: Kang Seong Su , Ahn Eun Hee , Ye Keqiang 
Published: August 2020

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease with age as a major risk factor. AD is the most common dementia with abnormal structures, including extracellular senile plaques and intraneuronal neurofibrillary tangles, as key neuropathologic hallmarks. The early feature of AD pathology is degeneration of the locus coeruleus (LC), which is the main source of norepinephrine (NE) supplying various cortical and subcortical areas that are affected in AD. The spread of Tau deposits is first initiated in the LC and is transported in a stepwise manner from the entorhinal cortex to the hippocampus and then to associative regions of the neocortex as the disease progresses. Most recently, we reported that the NE metabolite DOPEGAL activates delta-secretase (AEP, asparagine endopeptidase) and triggers pathological Tau aggregation in the LC, providing molecular insight into why LC neurons are selectively vulnerable to developing early Tau pathology and degenerating later in the disease and how δ-secretase mediates the spread of Tau pathology to the rest of the brain. This review summarizes our current understanding of the crucial role of δ-secretase in driving and spreading AD pathologies by cleaving multiple critical players, including APP and Tau, supporting that blockade of δ-secretase may provide an innovative disease-modifying therapeutic strategy for treating AD.
A clustering-independent method for finding differentially expressed genes in single-cell transcriptome data
Authors: Vandenbon Alexis , Diez Diego 
Published: August 2020

AbstractA common analysis of single-cell sequencing data includes clustering of cells and identifying differentially expressed genes (DEGs). How cell clusters are defined has important consequences for downstream analyses and the interpretation of results, but is often not straightforward. To address this difficulty, we present singleCellHaystack, a method that enables the prediction of DEGs without relying on explicit clustering of cells. Our method uses Kullback–Leibler divergence to find genes that are expressed in subsets of cells that are non-randomly positioned in a multidimensional space. Comparisons with existing DEG prediction approaches on artificial datasets show that singleCellHaystack has higher accuracy. We illustrate the usage of singleCellHaystack through applications on 136 real transcriptome datasets and a spatial transcriptomics dataset. We demonstrate that our method is a fast and accurate approach for DEG prediction in single-cell data. singleCellHaystack is implemented as an R package and is available from CRAN and GitHub.
Wnt activation as a therapeutic strategy in medulloblastoma
Authors: Manoranjan Branavan , Venugopal Chitra , Bakhshinyan David , Adile Ashley A. , Richards Laura , Kameda-Smith Michelle M. , Whitley Owen , Dvorkin-Gheva Anna , Subapanditha Minomi , Savage Neil , Tatari Nazanin , McKenna Dillon , Bassey-Archibong Blessing , Winegarden Neil , Hallett Robin , Provias John P. , Yarascavitch Blake , Ajani Olufemi , Fleming Adam , Bader Gary D. , Pugh Trevor J. , Doble Bradley W. , Singh Sheila K. 
Published: August 2020

AbstractMedulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/β-catenin signaling.
Defining the ATPome reveals cross-optimization of metabolic pathways
Authors: Bennett Neal K. , Nguyen Mai K. , Darch Maxwell A. , Nakaoka Hiroki J. , Cousineau Derek , ten Hoeve Johanna , Graeber Thomas G. , Schuelke Markus , Maltepe Emin , Kampmann Martin , Mendelsohn Bryce A. , Nakamura Jean L. , Nakamura Ken 
Published: August 2020

AbstractDisrupted energy metabolism drives cell dysfunction and disease, but approaches to increase or preserve ATP are lacking. To generate a comprehensive metabolic map of genes and pathways that regulate cellular ATP—the ATPome—we conducted a genome-wide CRISPR interference/activation screen integrated with an ATP biosensor. We show that ATP level is modulated by distinct mechanisms that promote energy production or inhibit consumption. In our system HK2 is the greatest ATP consumer, indicating energy failure may not be a general deficiency in producing ATP, but rather failure to recoup the ATP cost of glycolysis and diversion of glucose metabolites to the pentose phosphate pathway. We identify systems-level reciprocal inhibition between the HIF1 pathway and mitochondria; glycolysis-promoting enzymes inhibit respiration even when there is no glycolytic ATP production, and vice versa. Consequently, suppressing alternative metabolism modes paradoxically increases energy levels under substrate restriction. This work reveals mechanisms of metabolic control, and identifies therapeutic targets to correct energy failure.
Drop impact printing
Authors: Modak Chandantaru Dey , Kumar Arvind , Tripathy Abinash , Sen Prosenjit 
Published: August 2020

AbstractHydrodynamic collapse of a central air-cavity during the recoil phase of droplet impact on a superhydrophobic sieve leads to satellite-free generation of a single droplet through the sieve. Two modes of cavity formation and droplet ejection have been observed and explained. The volume of the generated droplet scales with the pore size. Based on this phenomenon, we propose a drop-on-demand printing technique. Despite significant advancements in inkjet technology, enhancement in mass-loading and particle-size have been limited due to clogging of the printhead nozzle. By replacing the nozzle with a sieve, we demonstrate printing of nanoparticle suspension with 71% mass-loading. Comparatively large particles of 20 μm diameter are dispensed in droplets of ~80 μm diameter. Printing is performed for surface tension as low as 32 mNm−1 and viscosity as high as 33 mPa∙s. In comparison to existing techniques, this way of printing is widely accessible as it is significantly simple and economical.
Intracellular sodium elevation reprograms cardiac metabolism
Authors: Aksentijević Dunja , Karlstaedt Anja , Basalay Marina V. , O’Brien Brett A. , Sanchez-Tatay David , Eminaga Seda , Thakker Alpesh , Tennant Daniel A. , Fuller William , Eykyn Thomas R. , Taegtmeyer Heinrich , Shattock Michael J. 
Published: August 2020

AbstractIntracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 μM ouabain 100 nM blebbistatin) or chronic myocardial Nai load (PLM3SA mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic ‘fingerprint’. Control (PLMWT), transgenic (PLM3SA), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by 23Na, 31P, 13C NMR followed by 1H-NMR metabolomic profiling. Elevated Nai leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Nai overload or inhibition of Na/Camito may be a new approach to ameliorate metabolic dysregulation in heart failure.
Disruption of Cav1.2-mediated signaling is a pathway for ketamine-induced pathology
Authors: Chen Huan , Vandorpe David H. , Xie Xiang , Alper Seth L. , Zeidel Mark L. , Yu Weiqun 
Published: August 2020

AbstractThe general anesthetic ketamine has been repurposed by physicians as an anti-depressant and by the public as a recreational drug. However, ketamine use can cause extensive pathological changes, including ketamine cystitis. The mechanisms of ketamine’s anti-depressant and adverse effects remain poorly understood. Here we present evidence that ketamine is an effective L-type Ca2+channel (Cav1.2) antagonist that directly inhibits calcium influx and smooth muscle contractility, leading to voiding dysfunction. Ketamine prevents Cav1.2-mediated induction of immediate early genes and transcription factors, and inactivation ofCav1.2in smooth muscle mimics the ketamine cystitis phenotype. Our results demonstrate that ketamine inhibition of Cav1.2 signaling is an important pathway mediating ketamine cystitis. In contrast, Cav1.2 agonist Bay k8644 abrogates ketamine-induced smooth muscle dysfunction. Indeed, Cav1.2 activation by Bay k8644 decreases voiding frequency while increasing void volume, indicating Cav1.2 agonists might be effective drugs for treatment of bladder dysfunction.
Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation
Authors: Park Doo Ri , Kim Jihee , Kim Gyeong Min , Lee Haeseung , Kim Minhee , Hwang Donghyun , Lee Hana , Kim Han-Sung , Kim Wankyu , Park Min Chan , Shim Hyunbo , Lee Soo Young 
Published: August 2020

AbstractOsteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.
Chromosome drives via CRISPR-Cas9 in yeast
Authors: Xu Hui , Han Mingzhe , Zhou Shiyi , Li Bing-Zhi , Wu Yi , Yuan Ying-Jin 
Published: August 2020

AbstractSelf-propagating drive systems are capable of causing non-Mendelian inheritance. Here, we report a drive system in yeast referred to as a chromosome drive that eliminates the target chromosome via CRISPR-Cas9, enabling the transmission of the desired chromosome. Our results show that the entire Saccharomyces cerevisiae chromosome can be eliminated efficiently through only one double-strand break around the centromere via CRISPR-Cas9. As a proof-of-concept experiment of this CRISPR-Cas9 chromosome drive system, the synthetic yeast chromosome X is completely eliminated, and the counterpart wild-type chromosome X harboring a green fluorescent protein gene or the components of a synthetic violacein pathway are duplicated by sexual reproduction. We also demonstrate the use of chromosome drive to preferentially transmit complex genetic traits in yeast. Chromosome drive enables entire chromosome elimination and biased inheritance on a chromosomal scale, facilitating genomic engineering and chromosome-scale genetic mapping, and extending applications of self-propagating drives.