bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Thermal 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

At 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

The 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

Rare 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

The 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

The 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

Alzheimer’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

A 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

Medulloblastoma (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

Disrupted 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

Hydrodynamic 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

Intracellular 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

The 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

Osteoarthritis (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

Self-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.
Rapid high-yield expression and purification of fully post-translationally modified recombinant clusterin and mutants
Authors: Satapathy Sandeep , Dabbs Rebecca A. , Wilson Mark R.
Published: August 2020

The first described and best known mammalian secreted chaperone, abundant in human blood, is clusterin. Recent independent studies are now exploring the potential use of clusterin as a therapeutic in a variety of disease contexts. In the past, the extensive post-translational processing of clusterin, coupled with its potent binding to essentially any misfolded protein, have meant that its expression as a fully functional recombinant protein has been very difficult. We report here the first rapid and high-yield system for the expression and purification of fully post-translationally modified and chaperone-active clusterin. Only 5–6 days is required from initial transfection to harvest of the protein-free culture medium containing the recombinant product. Purification to near-homogeneity can then be accomplished in a single affinity purification step and the yield for wild type human clusterin is of the order of 30–40 mg per litre of culture. We have also shown that this system can be used to quickly express and purify custom-designed clusterin mutants. These advances dramatically increase the feasibility of detailed structure–function analysis of the clusterin molecule and will facilitate identification of those specific regions responsible for the interactions of clusterin with receptors and other molecules.
Cholesterol 25-hydroxylase protects against experimental colitis in mice by modulating epithelial gut barrier function
Authors: Sheng Na , Ma Zhongnan , Zhou Yi , Xu Juan , Gao Yan , Fu Xin-Yuan
Published: August 2020

Cholesterol 25-hydroxylase (CH25H) encodes the enzyme that converts cholesterol to 25-hydroxycholesterol (25-HC). 25-HC has been demonstrated to be involved in the pathogenesis of inflammatory bowel disease. However, the role of CH25H in experimental colitis remains unknown. Dextran sulfate sodium (DSS)-induced colitis was monitored in wild type and Ch25h−/− mice in 8-week-old male for 7 days by assessment of body weight, histology, inflammatory cellular infiltration, and colon length. The function of CH25H was investigated using loss-of-function and gain-of-function such as Ch25h-deficient mice, supplementation with exogenous 25-HC and treatment of 25-HC into Caco2 and HCT116 colonic epithelial cells. Ch25h−/− mice with DSS-induced colitis exhibited aggravated injury, including higher clinical colitis scores, severe injury of the epithelial barrier, lower tight junction protein levels and higher levels of IL-6. Supplementation with exogenous 25-HC ameliorated disease symptoms and reduced the extent of damage in DSS-induced colitis, which was characterized by lower colon damage, higher tight junction protein expression, significantly decreased local and systemic production of pro-inflammatory cytokines IL-6. In Caco2 and HCT116 cells, 25-HC induced tight junction genes expression in colon cancer epithelial cells. These effects of CH25H were obtained by promoting ATF3 expression. Taken together, our findings reveal a protective role for 25-HC in DSS-induced colitis and the ability of CH25H to maintain epithelial gut barrier function through ATF3 expression. Supplementation with exogenous 25-HC ameliorates disease symptoms, which provides a new therapeutic strategy for ulcerative colitis.
XRN2 interactome reveals its synthetic lethal relationship with PARP1 inhibition
Authors: Patidar Praveen L. , Viera Talysa , Morales Julio C. , Singh Naveen , Motea Edward A. , Khandelwal Megha , Fattah Farjana J.
Published: August 2020

Persistent R-loops (RNA–DNA hybrids with a displaced single-stranded DNA) create DNA damage and lead to genomic instability. The 5′-3′-exoribonuclease 2 (XRN2) degrades RNA to resolve R-loops and promotes transcription termination. Previously, XRN2 was implicated in DNA double strand break (DSB) repair and in resolving replication stress. Here, using tandem affinity purification-mass spectrometry, bioinformatics, and biochemical approaches, we found that XRN2 associates with proteins involved in DNA repair/replication (Ku70-Ku80, DNA-PKcs, PARP1, MCM2-7, PCNA, RPA1) and RNA metabolism (RNA helicases, PRP19, p54(nrb), splicing factors). Novel major pathways linked to XRN2 include cell cycle control of chromosomal replication and DSB repair by non-homologous end joining. Investigating the biological implications of these interactions led us to discover that XRN2 depletion compromised cell survival after additional knockdown of specific DNA repair proteins, including PARP1. XRN2-deficient cells also showed enhanced PARP1 activity. Consistent with concurrent depletion of XRN2 and PARP1 promoting cell death, XRN2-deficient fibroblast and lung cancer cells also demonstrated sensitivity to PARP1 inhibition. XRN2 alterations (mutations, copy number/expression changes) are frequent in cancers. Thus, PARP1 inhibition could target cancers exhibiting XRN2 functional loss. Collectively, our data suggest XRN2’s association with novel protein partners and unravel synthetic lethality between XRN2 depletion and PARP1 inhibition.
Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo
Authors: Cai Songjie , Choi John Y. , Borges Thiago J. , Zhang Hengcheng , Miao Ji , Ichimura Takaharu , Li Xiaofei , Xu Simiao , Chu Philip , Eskandari Siawosh K. , Allos Hazim , Alhaddad Juliano B. , Muhsin Saif A. , Yatim Karim , Riella Leonardo V. , Sage Peter T. , Chandraker Anil K. , Azzi Jamil R.
Published: August 2020

Solid organ transplantation is a lifesaving therapy for patients with end-organ disease. Current immunosuppression protocols are not designed to target antigen-specific alloimmunity and are uncapable of preventing chronic allograft injury. As myeloid-derived suppressor cells (MDSCs) are potent immunoregulatory cells, we tested whether donor-derived MDSCs can protect heart transplant allografts in an antigen-specific manner. C57BL/6 (H2Kb, I-Ab) recipients pre-treated with BALB/c MDSCs were transplanted with either donor-type (BALB/c, H2Kd, I-Ad) or third-party (C3H, H2Kk, I-Ak) cardiac grafts. Spleens and allografts from C57BL/6 recipients were harvested for immune phenotyping, transcriptomic profiling and functional assays. Single injection of donor-derived MDSCs significantly prolonged the fully MHC mismatched allogeneic cardiac graft survival in a donor-specific fashion. Transcriptomic analysis of allografts harvested from donor-derived MDSCs treated recipients showed down-regulated proinflammatory cytokines. Immune phenotyping showed that the donor MDSCs administration suppressed effector T cells in recipients. Interestingly, significant increase in recipient endogenous CD11b+Gr1+ MDSC population was observed in the group treated with donor-derived MDSCs compared to the control groups. Depletion of this endogenous MDSCs with anti-Gr1 antibody reversed donor MDSCs-mediated allograft protection. Furthermore, we observed that the allogeneic mixed lymphocytes reaction was suppressed in the presence of CD11b+Gr1+ MDSCs in a donor-specific manner. Donor-derived MDSCs prolong cardiac allograft survival in a donor-specific manner via induction of recipient’s endogenous MDSCs.
Multiple ancestral haplotypes harboring regulatory mutations cumulatively contribute to a QTL affecting chicken growth traits
Authors: Wang Yuzhe , Cao Xuemin , Luo Chenglong , Sheng Zheya , Zhang Chunyuan , Bian Cheng , Feng Chungang , Li Jinxiu , Gao Fei , Zhao Yiqiang , Jiang Ziqin , Qu Hao , Shu Dingming , Carlborg Örjan , Hu Xiaoxiang , Li Ning
Published: August 2020

In depth studies of quantitative trait loci (QTL) can provide insights to the genetic architectures of complex traits. A major effect QTL at the distal end of chicken chromosome 1 has been associated with growth traits in multiple populations. This locus was fine-mapped in a fifteen-generation chicken advanced intercross population including 1119 birds and explored in further detail using 222 sequenced genomes from 10 high/low body weight chicken stocks. We detected this QTL that, in total, contributed 14.4% of the genetic variance for growth. Further, nine mosaic precise intervals (Kb level) which contain ancestral regulatory variants were fine-mapped and we chose one of them to demonstrate the key regulatory role in the duodenum. This is the first study to break down the detail genetic architectures for the well-known QTL in chicken and provides a good example of the fine-mapping of various of quantitative traits in any species.
The archives are half-empty: an assessment of the availability of microbial community sequencing data
Authors: Jurburg Stephanie D. , Konzack Maximilian , Eisenhauer Nico , Heintz-Buschart Anna
Published: August 2020

As DNA sequencing has become more popular, the public genetic repositories where sequences are archived have experienced explosive growth. These repositories now hold invaluable collections of sequences, e.g., for microbial ecology, but whether these data are reusable has not been evaluated. We assessed the availability and state of 16S rRNA gene amplicon sequences archived in public genetic repositories (SRA, EBI, and DDJ). We screened 26,927 publications in 17 microbiology journals, identifying 2015 16S rRNA gene sequencing studies. Of these, 7.2% had not made their data public at the time of analysis. Among a subset of 635 studies sequencing the same gene region, 40.3% contained data which was not available or not reusable, and an additional 25.5% contained faults in data formatting or data labeling, creating obstacles for data reuse. Our study reveals gaps in data availability, identifies major contributors to data loss, and offers suggestions for improving data archiving practices.
Diversity in the intrinsic apoptosis pathway of nematodes
Authors: Young Neil D. , Harris Tiffany J. , Evangelista Marco , Tran Sharon , Wouters Merridee A. , Soares da Costa Tatiana P. , Kershaw Nadia J. , Gasser Robin B. , Smith Brian J. , Lee Erinna F. , Fairlie W. Douglas
Published: August 2020

Early studies of the free-living nematode C. elegans informed us how BCL-2-regulated apoptosis in humans is regulated. However, subsequent studies showed C. elegans apoptosis has several unique features compared with human apoptosis. To date, there has been no detailed analysis of apoptosis regulators in nematodes other than C. elegans. Here, we discovered BCL-2 orthologues in 89 free-living and parasitic nematode taxa representing four evolutionary clades (I, III, IV and V). Unlike in C. elegans, 15 species possess multiple (two to five) BCL-2-like proteins, and some do not have any recognisable BCL-2 sequences. Functional studies provided no evidence that BAX/BAK proteins have evolved in nematodes, and structural studies of a BCL-2 protein from the basal clade I revealed it lacks a functionally important feature of the C. elegans orthologue. Clade I CED-4/APAF-1 proteins also possess WD40-repeat sequences associated with apoptosome assembly, not present in C. elegans, or other nematode taxa studied.
Mass spectrometry-based identification of ortho-, meta- and para-isomers using infrared ion spectroscopy
Authors: van Outersterp Rianne E. , Martens Jonathan , Berden Giel , Koppen Valerie , Cuyckens Filip , Oomens Jos
Published: August 2020

Distinguishing positional isomers presents a significant challenge for mass spectrometric analyses, for instance in drug metabolism research. We show that IR ion spectroscopy readily identifies ortho-, meta- and para-isomers.
A novel eco-friendly green approach to produce particalized eggshell membrane (PEM) for skin health applications
Authors: Kulshreshtha Garima , Ahmed Tamer A. E. , Wu Ling , Diep Ty , Hincke Maxwell T.
Published: August 2020

The eggshell membrane (ESM) is a natural bioactive material, which is increasingly utilized for various biomedical applications.
Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors
Authors: Seixas João D. , Sousa Bárbara B. , Marques Marta C. , Guerreiro Ana , Traquete Rui , Rodrigues Tiago , Albuquerque Inês S. , Sousa Marcos F. Q. , Lemos Ana R. , Sousa Pedro M. F. , Bandeiras Tiago M. , Wu Di , Doyle Shelby K. , Robinson Carol V. , Koehler Angela N. , Corzana Francisco , Matias Pedro M. , Bernardes Gonçalo J. L.
Published: August 2020

We identified potent, functionalisable BMX inhibitors and revealed their covalent mode of binding to BMX by X-ray crystallography.
Ionothermal synthesis of crystalline metal phosphites using multifunctional protic ionic liquids
Authors: Li Ting , Mao Yumei , Qi Yue , Zeng Hongmei , Zou Guohong , Lin Zhien
Published: August 2020

A mixed-valence iron phosphite was prepared under ionothermal conditions using a protic ionic liquid as a solvent, a structure-directing agent, a phosphorus source, and a reducing agent.
Recombination mechanisms of luminescence type gas sensors
Authors: Poeplau Michael , Ester Stephan , Henning Bernd , Wagner Thorsten
Published: August 2020

The impact of the recombination mechanisms in luminescent materials is discussed with regard to luminescence based gas-sensing applications and the use of semiconducting materials, as an alternative to organic–metal complexes, is outlined.
Elucidation of distinct fluorescence and room-temperature phosphorescence of organic polymorphs from benzophenone–borate derivatives
Authors: Che Weilong , Gong Yanbin , Tu Liangjing , Han Mengmeng , Li Xiaoning , Xie Yujun , Li Zhen
Published: August 2020

The RTP property of polymorphisms present the different emission derive from the same molecule embed in different intermolecular packings.
Exploring charge density distribution and electronic properties of hybrid organic-germanium layers
Authors: Bento de Oliveira Flávio , Lima Erika Nascimento , da Silva Mauricio Chagas , da Rosa Andreia Luisa , Frauenheim Thomas
Published: August 2020

Theoretical bond characterization of ligand modified germanene structures.
Intrinsic folding of the cysteine residue: competition between folded and extended forms mediated by the –SH group
Authors: Goldsztejn Gildas , Mundlapati Venkateswara Rao , Brenner Valérie , Gloaguen Eric , Mons Michel , Cabezas Carlos , León Iker , Alonso José Luis
Published: August 2020

A dual microwave and optical spectroscopic study of a capped cysteine amino acid isolated in a supersonic expansion, combined with quantum chemistry modelling, enabled us to access the conformational preferences of Cys embedded in a protein chain.
Vibrational energy relaxation of interfacial OH on a water-covered α-Al2O3(0001) surface: a non-equilibrium ab initio molecular dynamics study
Authors: Melani Giacomo , Nagata Yuki , Saalfrank Peter
Published: August 2020

Vibrational dynamics and relaxation of excited non-hydrogen bonded OH-aluminols from non-equilibrium AIMD, towards in silico time-resolved VSF experiments.
Accelerated ageing reactions: towards simpler, solvent-free, low energy chemistry
Authors: Huskić Igor , Lennox Cameron B. , Friščić Tomislav
Published: August 2020

Accelerated ageing reactions proceed spontaneously in mixtures of solid reactants, and provide a route towards developing solvent- and energy-free chemistry.
Exosome trapping and enrichment using a sound wave activated nano-sieve (SWANS)
Authors: Habibi Ruhollah , He Vincent , Ghavamian Sara , de Marco Alex , Lee Tzong-Hsien , Aguilar Marie-Isabel , Zhu Dandan , Lim Rebecca , Neild Adrian
Published: August 2020

Mechanically activated packed-bed of beads (SWANS) traps and rapidly enriches the concentration of exosomes, a form of extracellular vesicles, while preserves the integrity of the lipid bilayer membrane. Also, larger beads perform better in capturing.
Zinc-triggered photocatalytic selective synthesis of benzyl acetate on inverse spinel CuFe2O4 3D networks: a case of coupled redox photocatalytic reaction
Authors: Zhang Yihan , Tian Jingqi , Jiang Tengfei , Xue Huaiguo
Published: August 2020

A zinc dopant in CuFe2O4 3D networks triggers the selectivity of benzaldehyde to benzyl acetate via a coupled redox photocatalytic (CRP) reaction.
Synthesis and catalytic evaluation of PVP–CeO2/rGO as a highly efficient and recyclable heterogeneous catalyst for multicomponent reactions in water
Authors: Siddiqui Shaheen , Siddiqui Zeba N.
Published: August 2020

PVP–CeO2/rGO: synthesis, characterization and application in multicomponent reactions.
Plasmonic-based sensitivity enhancement of a Goos–Hänchen shift biosensor using transition metal dichalcogenides: a theoretical insight
Authors: Guo Yan , Singh Nishtha Manish , Manas Das Chandreyee , Ouyang Qingling , Kang Lixing , Li Kuanbiao , Coquet Philippe , Yong Ken-Tye
Published: August 2020

Layered transition metal dichalcogenides (TMDCs) within two dimension (2D) have been gaining widespread consideration due to their exclusive optoelectronic properties.
Synthesis of gold nanoparticle-loaded magnetic carbon microsphere based on reductive and binding properties of polydopamine for recyclable catalytic applications
Authors: Xu Qiang , Gao Taiping , Zhang Shengxiao , Zhang Mingming , Li Xin , Liu Xia
Published: August 2020

A hierarchical nanostructure of Fe3O4@C–Au, with Fe3O4 as a core and carbon as a shell, was synthesized using a simple method.
Theoretical study on the photocatalytic properties of 2D InX(X = S, Se)/transition metal disulfide (MoS2and WS2) van der Waals heterostructures
Authors: Guo Hailing , Zhang Zhaofu , Huang Bingquan , Wang Xiting , Niu Huan , Guo Yuzheng , Li Baikui , Zheng Ruisheng , Wu Honglei
Published: August 2020

Harvesting solar energy for artificial photosynthesis is an emerging field in alternative energy research.
A N-bridged strategy enables hemilabile phosphine–carbonyl palladium and nickel catalysts to mediate ethylene polymerization and copolymerization with polar vinyl monomers
Authors: Cui Lei , Jian Zhongbao
Published: August 2020

N-Bridged phosphine–carbonyl Pd(ii) and Ni(ii) catalysts enable the enhancement of molecular weights in ethylene polymerization and copolymerization with polar comonomers.
UsingFomitopsis pinicolafor bioinspired synthesis of titanium dioxide and silver nanoparticles, targeting biomedical applications
Authors: Rehman Suriya , Jermy Rabindran , Mousa Asiri Sarah , Shah Manzoor A. , Farooq Romana , Ravinayagam Vijaya , Azam Ansari Mohammad , Alsalem Zainab , Al Jindan Reem , Reshi Zafar , Khan Firdos Alam
Published: August 2020

This study proposes a bio-directed approach for the formation of titanium oxide and silver nanoparticles (TiO2and Ag NPs), using a wild mushroom,Fomitopsis pinicola, identified by 18S ribosomal RNA gene sequencing (gene accession no. MK635350) and phenotypic examination.
1,4-Dithiolbenzene, 1,4-dimethanediolbenzene and 4-thioacetylbiphenyl molecular systems: electronic devices with possible applications in molecular electronics
Authors: Ojeda J. H. , Piracón Muñoz Lina K. , Guerra Pinzón Julian A. , Gómez Castaño Jovanny A.
Published: August 2020

A theoretical study of the electronic transport properties of the 1,4-dithiolbenzene, 1,4-dimethanediolbenzene and 4-thioacetylbiphenyl molecules coupled to two metal contacts is carried out.
Droplet fluid infusion into a dust layer in relation to self-cleaning
Authors: Hassan Ghassan , Yilbas Bekir Sami , Al-Qahtani Hussain
Published: August 2020

Wettability of a droplet liquid on a dusty hydrophobic plate is considered and the fluid infusion into the dust layer is studied pertinent to dust removal from the hydrophobic surfaces via rolling/sliding droplets.
Effective removal of aromatic pollutants via adsorption and photocatalysis of porous organic frameworks
Authors: Wang Congcong , Wang Wei , Wang Jian , Zhang Peiping , Miao Shiding , Jin Bo , Li Lina
Published: August 2020

PAF-45 with a wholly aromatic framework, intrinsic microporosity and π–π conjugation system shows excellent performance in aromatic pollutant removal.
Quercetin loaded folate targeted plasmonic silver nanoparticles for light activated chemo-photothermal therapy of DMBA induced breast cancer in Sprague Dawley rats
Authors: Bose Pritha , Priyam Amiya , Kar Rajiv , Pattanayak Shakti P.
Published: August 2020

Novel plasmonic (>800 nm) pentagonal QRC-FA-AgNPs synthesized through simple chemical technique induces light activated combined chemo-photothermal efficacy against breast cancer.
Retracted Article: The synthesis and biological activity of marine alkaloid derivatives and analogues
Authors: Zhou Shiyang , Huang Gangliang
Published: August 2020

The ocean is the origin of life, with a unique ecological environment, which has given birth to a wealth of marine organisms.
Elaborating piperazinyl-furopyrimidine based scaffolds as phosphoinositol-3-kinase enzyme alpha (PI3Kα) inhibitors to combat pancreatic cancer
Authors: Mansour Mai A. , Lasheen Deena S. , Gaber Hatem M. , Abouzid Khaled A. M.
Published: August 2020

Phosphoinositol-3-kinase alpha (PI3K-α) enzyme inhibition to combat pancreatic cancer.
A rationally designed peptoid for the selective chelation of Zn2+ over Cu2+
Authors: Ghosh Pritam , Maayan Galia
Published: August 2020

A peptoid trimer incorporating picolyl 2,2′:6′,2′′-terpyridine can selectively bind Zn2+ ions in the presence of excess Cu2+ ions and other metal ions, in water and in simulated body fluid (SBF) and can remove Zn2+ from a natural zinc protein in SBF.
Reductive catalytic fractionation of lignocellulose: when should the catalyst meet depolymerized lignin fragments?
Authors: Qiu Shi , Wang Meng , Fang Yunming , Tan Tianwei
Published: August 2020

Immediate stabilization in the RCF process is essential, and delignification and stabilization can be split under certain conditions.
Caregivers' Perceptions of Speech-Language Pathologist Talk About Child Language and Literacy Disorders
Authors: Porter Karmen L. , Oetting Janna B. , Pecchioni Loretta
Published: August 2020

Purpose

This study examined caregiver perceptions of their child's language and literacy disorder as influenced by communications with their speech-language pathologist.

Method

The participants were 12 caregivers of 10 school-aged children with language and literacy disorders. Employing qualitative methods, a collective case study approach was utilized in which the caregiver(s) of each child represented one case. The data came from semistructured interviews, codes emerged directly from the caregivers' responses during the interviews, and multiple coding passes using ATLAS.ti software were made until themes were evident. These themes were then further validated by conducting clinical file reviews and follow-up interviews with the caregivers.

Results

Caregivers' comments focused on the types of information received or not received, as well as the clarity of the information. This included information regarding their child's diagnosis, the long-term consequences of their child's disorder, and the connection between language and reading. Although caregivers were adept at describing their child's difficulties and therapy goals/objectives, their comments indicated that they struggled to understand their child's disorder in a way that was meaningful to them and their child.

Conclusions

The findings showed the value caregivers place on receiving clear and timely diagnostic information, as well as the complexity associated with caregivers' understanding of language and literacy disorders. The findings are discussed in terms of changes that could be made in clinical practice to better support children with language and literacy disorders and their families.
Kernel nullers for an arbitrary number of apertures
Authors: Laugier Romain , Cvetojevic Nick , Martinache Frantz
Published: August 2020

Context.The use of interferometric nulling for the direct detection of extrasolar planets is in part limited by the extreme sensitivity of the instrumental response to tiny optical path differences between apertures. The recently proposed kernel-nuller architecture attempts to alleviate this effect with an all-in-one combiner design that enables the production of observables inherently robust to residual optical path differences (≪λ).

Aims.To date, a unique kernel-nuller design has been proposed ad hoc for a four-beam combiner. We examine the properties of this original design and generalize them for an arbitrary number of apertures.

Methods.We introduce a convenient graphical representation of the complex combiner matrices that model the kernel nuller and highlight the symmetry properties that enable the formation of kernel nulls. The analytical description of the nulled outputs we provide demonstrates the properties of a kernel nuller.

Results.Our description helps outline a systematic way to build a kernel nuller for an arbitrary number of apertures. The designs for three- and six-input combiners are presented along with the original four-input concept. The combiner grows in complexity with the square of the number of apertures. While one can mitigate this complexity by multiplexing nullers working independently over a smaller number of sub-apertures, an all-in-one kernel nuller recombining a large number of apertures appears as the most efficient way to characterize a high-contrast complex astrophysical scene.

Conclusions.Kernel nullers can be designed for an arbitrary number of apertures that produce observable quantities robust to residual perturbations. The designs we recommend are lossless and take full advantage of all the available interferometric baselines. They are complete, result in as many kernel nulls as the theoretically expected number of closure-phases, and are optimized to require the smallest possible number of outputs.
Research of a three-dimensional nonlinear dynamic system describing the process of two-level assimilation
Authors: Chilachava Temur , Pochkhua George
Published: August 2020

The work proposes a new general nonlinear mathematical model describing the social process of two-level assimilation taking into account quadratic members of self-restriction of population growth of three sides. In the case of constant coefficients of the model, the first integral of a three-dimensional dynamic system has been found, which in the phase space of solutions is a cone. The three-dimensional dynamic system is reduced to two-dimensional and with the help of the Bendixon’s criterion the theorem of existence in the first quarter of the phase plane of the closed integral trajectory is proved. Thus, conditions on model parameters are found that do not fully assimilate the third side.