bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiphospholipid Antibodies Inhibit Trophoblast Toll‐Like Receptor and Inflammasome Negative Regulators
Authors: Mulla Melissa J. , Weel Ingrid C. , Potter Julie A. , Gysler Stefan M. , Salmon Jane E. , Peraçoli Maria T. S. , Rothlin Carla V. , Chamley Lawrence W. , Abrahams Vikki M. 
Published: January 2018

ObjectiveWomen with antiphospholipid antibodies (aPL) are at risk for pregnancy complications associated with poor placentation and placental inflammation. Although these antibodies are heterogeneous, some anti–β2‐glycoprotein I (anti‐β2GPI) antibodies can activate Toll‐like receptor 4 (TLR‐4) and NLRP3 in human first‐trimester trophoblasts. The objective of this study was to determine the role of negative regulators of TLR and inflammasome function in aPL‐induced trophoblast inflammation.MethodsHuman trophoblasts were not treated or were treated with anti‐β2GPI aPL or control IgG in the presence or absence of the common TAM (TYRO3, AXL, and Mer tyrosine kinase [MERTK]) receptor ligand growth arrest–specific protein 6 (GAS6) or the autophagy‐inducer rapamycin. The expression and function of the TAM receptor pathway and autophagy were measured by quantitative reverse transcription–polymerase chain reaction (qRT‐PCR), Western blotting, and enzyme‐linked immunosorbent assay (ELISA). Antiphospholipid antibody–induced trophoblast inflammation was measured by qRT‐PCR, activity assays, and ELISA.ResultsAnti‐β2GPI aPL inhibited trophoblast TAM receptor function by reducing cellular expression of the receptor tyrosine kinases AXL and MERTK and the ligand GAS6. The addition of GAS6 blocked the effects of aPL on the TLR‐4–mediated interleukin‐8 (IL‐8) response. However, the NLRP3 inflammasome‐mediated IL‐1β response was not affected by GAS6, suggesting that another regulatory pathway was involved. Indeed, anti‐β2GPI aPL inhibited basal trophoblast autophagy, and reversing this with rapamycin inhibited aPL‐induced inflammasome function and IL‐1β secretion.ConclusionBasal TAM receptor function and autophagy may serve to inhibit trophoblast TLR and inflammasome function, respectively. Impairment of TAM receptor signaling and autophagy by anti‐β2GPI aPL may allow subsequent TLR and inflammasome activity, leading to a robust inflammatory response.
Molecular Basis for Dysregulated Activation of NKX2‐5 in the Vascular Remodeling of Systemic Sclerosis
Authors: Dritsoula Athina , Papaioannou Ioannis , Guerra Sandra G. , Fonseca Carmen , Martin Javier , Herrick Ariane L. , Abraham David J. , Denton Christopher P. , Ponticos Markella 
Published: January 2018

ObjectiveNKX2‐5 is a homeobox transcription factor that is required for the formation of the heart and vessels during development, with significant postnatal down‐regulation and reactivation in disease states, characterized by vascular remodeling. The purpose of this study was to investigate mechanisms that activate NKX2‐5 expression in diseased vessels, such as systemic sclerosis (scleroderma; SSc)–associated pulmonary hypertension (PH), and to identify genetic variability that potentially underlies susceptibility to specific vascular complications.MethodsWe explored NKX2‐5 expression in biopsy samples from patients with SSc‐associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients with scleroderma. Disease‐associated putative functional single‐nucleotide polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene assays. SNP function was further examined through protein–DNA binding assays, chromatin immunoprecipitation assays, and RNA silencing analyses.ResultsIncreased NKX2‐5 expression in biopsy samples from patients with SSc‐associated PH was localized to remodeled vessels and PASMCs. Meta‐analysis of 2 independent scleroderma cohorts revealed an association of rs3131917 with scleroderma (P = 0.029). We demonstrated that disease‐associated SNPs are located in a novel functional enhancer, which increases NKX2-5 transcriptional activity through the binding of GATA‐6, c‐Jun, and myocyte‐specific enhancer factor 2C. We also characterized an activator/coactivator transcription‐enhancer factor domain 1 (TEAD1)/Yes‐associated protein 1 (YAP1) complex, which was bound at rs3095870, another functional SNP, with TEAD1 binding the risk allele and activating the transcription of NKX2-5.ConclusionNKX2-5 is genetically associated with scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs through the interaction of an upstream promoter and a novel downstream enhancer. This mechanism can act as a model for NKX2‐5 activation in cardiovascular disease characterized by vascular remodeling.
Altered functional networks in long‐term unilateral hearing loss: A connectome analysis
Authors: Zhang Yanyang , Mao Zhiqi , Feng Shiyu , Liu Xinyun , Lan Lan , Zhang Jun , Yu Xinguang 
Published: January 2018

AbstractIntroductionIn neuroimaging studies, long‐term unilateral hearing loss (UHL) is associated with functional changes in specific brain regions and connections; however, little is known regarding alterations in the topological organization of whole‐brain functional networks and whether these alterations are related to hearing behavior in UHL patients.MethodsWe acquired resting‐state fMRI data from 21 patients with UHL caused by acoustic neuromas and 21 matched healthy controls. Whole‐brain functional networks were constructed by measuring interregional temporal correlations of 278 brain regions. Alterations in interregional functional connectivity and topological properties (e.g., small‐world, efficiency, and nodal centrality) were identified using graph‐theory analysis. The subjects also completed a battery of hearing behavior measures.ResultsBoth UHL patients and controls exhibited efficient small‐world properties in their functional networks. Compared with controls, UHL patients showed increased and decreased nodal centrality in distributed brain regions. Furthermore, the brain regions with significantly increased and decreased functional connections associated with UHL were components of the following important networks: (1) visual network; (2) higher‐order functional networks, including the default‐mode and attention networks; and (3) subcortical network and cerebellum. Intriguingly, the changes in intranetwork connections in UHL were significantly correlated with disease duration and hearing level.ConclusionsThis study revealed connectome‐level alterations involved in multiple large‐scale networks related to sensory and higher‐level cognitive functions in long‐term UHL patients. These reorganizations of the brain in UHL patients may depend on the stage of deafness and hearing level. Together, our findings provided empirical evidence for understanding the neuroplastic mechanisms underlying hearing impairment, establishing potential biomarkers for monitoring the progression and further treatment effects for UHL patients.
WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP‐14 pathway
Authors: Wang Xingwen , Zhao Xin , Yi Zhigang , Ma Bing , Wang Hong , Pu Yanchuan , Wang Jing , Wang Shuanke 
Published: January 2018

AbstractWNT5A, a representative ligand of activating several non‐canonical WNT signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non‐receptor tyrosine kinase SRC is required for WNT5A‐induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC‐mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC‐induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and invasion of human osteosarcoma MG‐63 cells, whereas inhibiting either SRC kinase activity by siRNA‐mediated SRC silence or ERK1/2 phosphorylation by PD98059 treatment suppressed these effects, which suggested that the activation of SRC and ERK1/2 is essential for WNT5A‐induced MG‐63 cells migration and invasion. Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by SRC siRNA. Additionally, our study further demonstrated that MMP‐14 was upregulated after exposure to WNT5A in MG‐63 cells, and the increased expression was blocked by SRC siRNA or PD98059. Collectively, these results indicate that WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP‐14 expression and MG‐63 cells migration and invasion.
Glycine improves the remodeling process of tenocytes in vitro
Authors: Vieira Cristiano Pedrozo , Viola Manuela , Carneiro Giane Daniela , D'Angelo Maria Luisa , Vicente Cristina Pontes , Passi Alberto , Pimentel Edson Rosa 
Published: January 2018

AbstractTendinitis changes the biochemical and morphological properties of the tendon, promoting an increase of activity of metalloproteinases and disorganization of collagen bundles. Tenocytes, the primary cells in tendon, are scattered throughout the collagenic fibers, and are responsible of tendon remodeling and tissue repair in pathological condition. In vivo, glycine, component of the typical Gly‐X‐Y collagen tripeptide, showed beneficial effects in biochemical and biomechanical properties of Achilles tendon with tendinitis. In this study, we analyzed the effect of glycine in tenocytes subjected to inflammation. Tenocytes from Achilles tendon of rats were treated with TNF‐α (10 ng/mL) with and without previous treatment with glycine (20 mM). Cell proliferation and migration were evaluated, as well as the expression of matrix molecules such as glycosaminoglycans, metalloproteinases (MMPs), TIMPs, and collagen I. Glycine can revert the inflammation due to the action of TNF‐α by controlling the MMPs quantity and activity. These data indicated that the molecules involved to remodeling process of extracellular matrix are modulated both by TNF‐α and the availability of collagen precursors; in fact, this study indicates the glycine can be useful for treatment of inflammation and for modulating tenocytes metabolism in tendons.
Primary growth hormone insensitivity and psychomotor delay
Authors: Castilla‐Cortazar Inma , De Ita Julieta Rodríguez , Aguirre Gabriel A. , Rodríguez‐Rivera Joel , García‐Magariño Mariano , Martín‐Estal Irene , Flores‐Caloca Óscar , Diaz‐Olachea Carlos 
Published: January 2018

Key Clinical MessageWe report a case of short stature irresponsive to growth hormone (GH) replacement therapy. LowGHresponse to provocative tests and undetectableIGF‐1 levels had suggestedGHdeficiency, while response to therapy indicatedGHinsensitivity. Molecular evaluation of theGH/IGF‐1 axis should be performed in these cases to improve diagnosis and therapy.
Laboratory Simulation of an Agricultural Biogas Plant Start‐up
Authors: Kozłowski Kamil , Dach Jacek , Lewicki Andrzej , Cieślik Marta , Czekała Wojciech , Janczak Damian , Brzoski Michał 
Published: January 2018

AbstractDue to the large energy potential of biofuel production, in the near future the construction of new biogas plants in Poland is expected. However, prior to any investment in the biogas market it is necessary to conduct performance tests of methane production from the used substrates and to perform simulation of the initial start‐up on a laboratory scale. The start‐up of agricultural biogas plants on a laboratory scale is simulated using pig slurry and maize silage. In this lab‐scale simulation, the same conditions of running are created as for real‐scale biogas installation. The research tests prove the suitability of advanced continuous stirring‐tank reactors (CSTRs) to optimize the operation of biogas installations on a real scale.
Exact Mapping from Many‐Spin Hamiltonians to Giant‐Spin Hamiltonians
Authors: Ghassemi Tabrizi Shadan , Arbuznikov Alexei V. , Kaupp Martin 
Published: January 2018

AbstractThermodynamic and spectroscopic data of exchange‐coupled molecular spin clusters (e.g. single‐molecule magnets) are routinely interpreted in terms of two different models: the many‐spin Hamiltonian (MSH) explicitly considers couplings between individual spin centers, while the giant‐spin Hamiltonian (GSH) treats the system as a single collective spin. When isotropic exchange coupling is weak, the physical compatibility between both spin Hamiltonian models becomes a serious concern, due to mixing of spin multiplets by local zero‐field splitting (ZFS) interactions (′S‐mixing′). Until now, this effect, which makes the mapping MSH→GSH (′spin projection′) non‐trivial, had only been treated perturbationally (up to third order), with obvious limitations. Here, based on exact diagonalization of the MSH, canonical effective Hamiltonian theory is applied to construct a GSH that exactly matches the energies of the relevant (2S+1) states comprising an effective spin multiplet. For comparison, a recently developed strategy for the unique derivation of effective (′pseudospin′) Hamiltonians, now routinely employed in ab initio calculations of mononuclear systems, is adapted to the problem of spin projection. Expansion of the zero‐field Hamiltonian and the magnetic moment in terms of irreducible tensor operators (or Stevens operators) yields terms of all ranks k (up to k=2S) in the effective spin. Calculations employing published MSH parameters illustrate exact spin projection for the well‐investigated [Ni(hmp)(dmb)Cl]4 (′Ni4′) single‐molecule magnet, which displays weak isotropic exchange (dmb=3,3‐dimethyl‐1‐butanol, hmp− is the anion of 2‐hydroxymethylpyridine). The performance of the resulting GSH in finite field is assessed in terms of EPR resonances and diabolical points. The large tunnel splitting in the M=
4 ground doublet of the S=4 multiplet, responsible for fast tunneling in Ni4, is attributed to a Stevens operator with eightfold rotational symmetry, marking the first quantification of a k=8 term in a spin cluster. The unique and exact mapping MSH→GSH should be of general importance for weakly‐coupled systems; it represents a mandatory ultimate step for comparing theoretical predictions (e.g. from quantum‐chemical calculations) to ZFS, hyperfine or g‐tensors from spectral fittings.
Production of Alternative Liquid Fuels in the Future Energy System
Authors: Dietrich Ralph‐Uwe , Albrecht Friedemann , Pregger Thomas 
Published: January 2018

AbstractDer vorliegende Beitrag skizziert einen möglichen zukünftigen Bedarf an erneuerbaren flüssigen Kraftstoffen, bewertet mögliche Prozessrouten zu deren Erzeugung im großen Maßstab unter Einsatz von erneuerbarem Strom, Biomasse und anderen Kohlenstoffquellen und diskutiert systemische Effekte eines entsprechenden Infrastrukturausbaus. Die in einer Fallstudie erfolgte technische, ökonomische und ökologische Bewertung basiert auf detaillierten Prozesssimulationen verknüpft mit dem Kostenberechnungstool TEPET und ermöglicht so eine größtmögliche Transparenz aus wissenschaftlicher Sicht.
Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules
Authors: Nikiforova Marina N. , Mercurio Stephanie , Wald Abigail I. , Barbi de Moura Michelle , Callenberg Keith , Santana‐Santos Lucas , Gooding William E. , Yip Linwah , Ferris Robert L. , Nikiforov Yuri E. 
Published: January 2018

BACKGROUNDMolecular tests have clinical utility for thyroid nodules with indeterminate fine‐needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test.METHODSThyroSeq v3 is a DNA‐ and RNA‐based next‐generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions. It was validated in 238 tissue samples and 175 FNA samples with known surgical follow‐up. Analytical performance studies were conducted.RESULTSIn the training tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations, including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions, 22q loss, and gene expression alterations. GC cutoffs were established to distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity, and 92.1% accuracy. This correctly classified most papillary, follicular, and Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%, and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content, and reproducible test results under variable stress conditions.CONCLUSIONSThe ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides high accuracy for detecting all common types of thyroid cancer and parathyroid lesions. The analytical sensitivity, specificity, and robustness of the test have been successfully validated and indicate its suitability for clinical use. Cancer 2018;124:1682‐90. © 2018 American Cancer Society
Live‐Animal Imaging of Renal Function by Multiphoton Microscopy
Authors: Dunn Kenneth W. , Sutton Timothy A. , Sandoval Ruben M. 
Published: January 2018

AbstractIntravital microscopy, microscopy of living animals, is a powerful research technique that combines the resolution and sensitivity found in microscopic studies of cultured cells with the relevance and systemic influences of cells in the context of the intact animal. The power of intravital microscopy has recently been extended with the development of multiphoton fluorescence microscopy systems capable of collecting optical sections from deep within the kidney at subcellular resolution, supporting high‐resolution characterizations of the structure and function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent probes are administered to an anesthetized, surgically prepared animal, followed by image acquisition for up to 3 hr. Images are transferred via a high‐speed network to specialized computer systems for digital image analysis. This general approach can be used with different combinations of fluorescent probes to evaluate processes such as glomerular permeability, proximal tubule endocytosis, microvascular flow, vascular permeability, mitochondrial function, and cellular apoptosis/necrosis. © 2018 by John Wiley & Sons, Inc.
Generating Quantitative Cell Identity Labels with Marker Enrichment Modeling (MEM)
Authors: Diggins Kirsten E. , Gandelman Jocelyn S. , Roe Caroline E. , Irish Jonathan M. 
Published: January 2018

AbstractMultiplexed single‐cell experimental techniques like mass cytometry measure 40 or more features and enable deep characterization of well‐known and novel cell populations. However, traditional data analysis techniques rely extensively on human experts or prior knowledge, and novel machine learning algorithms may generate unexpected population groupings. Marker enrichment modeling (MEM) creates quantitative identity labels based on features enriched in a population relative to a reference. While developed for cell type analysis, MEM labels can be generated for a wide range of multidimensional data types, and MEM works effectively with output from expert analysis and diverse machine learning algorithms. MEM is implemented as an R package and includes three steps: (1) calculation of MEM values that quantify each feature's relative enrichment in the population, (2) reporting of MEM labels as a heatmap or as a text label, and (3) quantification of MEM label similarity between populations. The protocols here show MEM analysis using datasets from immunology and oncology. These MEM implementations provide a way to characterize population identity and novelty in the context of computational and expert analyses. © 2018 by John Wiley & Sons, Inc.
Landscape simplification reduces classical biological control and crop yield
Authors: Grab Heather , Danforth Bryan , Poveda Katja , Loeb Greg 
Published: January 2018

AbstractAgricultural intensification resulting in the simplification of agricultural landscapes is known to negatively impact the delivery of key ecosystem services such as the biological control of crop pests. Both conservation and classical biological control may be influenced by the landscape context in which they are deployed; yet studies examining the role of landscape structure in the establishment and success of introduced natural enemies and their interactions with native communities are lacking. In this study, we investigated the relationship between landscape simplification, classical and conservation biological control services and importantly, the outcome of these interactions for crop yield. We showed that agricultural simplification at the landscape scale is associated with an overall reduction in parasitism rates of crop pests. Additionally, only introduced parasitoids were identified, and no native parasitoids were found in crop habitat, irrespective of agricultural landscape simplification. Pest densities in the crop were lower in landscapes with greater proportions of semi‐natural habitats. Furthermore, farms with less semi‐natural cover in the landscape and consequently, higher pest numbers, had lower yields than farms in less agriculturally dominated landscapes. Our study demonstrates the importance of landscape scale agricultural simplification in mediating the success of biological control programs and highlights the potential risks to native natural enemies in classical biological control programs against native insects. Our results represent an important contribution to an understanding of the landscape‐mediated impacts on crop yield that will be essential to implementing effective policies that simultaneously conserve biodiversity and ecosystem services.
Refining mortality estimates in shark demographic analyses: a Bayesian inverse matrix approach
Authors: Smart Jonathan J. , Punt André E. , Espinoza Mario , White William T. , Simpfendorfer Colin A. 
Published: January 2018

AbstractLeslie matrix models are an important analysis tool in conservation biology that are applied to a diversity of taxa. The standard approach estimates the finite rate of population growth (λ) from a set of vital rates. In some instances, an estimate of λ is available, but the vital rates are poorly understood and can be solved for using an inverse matrix approach. However, these approaches are rarely attempted due to prerequisites of information on the structure of age or stage classes. This study addressed this issue by using a combination of Monte Carlo simulations and the sample‐importance‐resampling (SIR) algorithm to solve the inverse matrix problem without data on population structure. This approach was applied to the grey reef shark (Carcharhinus amblyrhynchos) from the Great Barrier Reef (GBR) in Australia to determine the demography of this population. Additionally, these outputs were applied to another heavily fished population from Papua New Guinea (PNG) that requires estimates of λ for fisheries management. The SIR analysis determined that natural mortality (M) and total mortality (Z) based on indirect methods have previously been overestimated for C. amblyrhynchos, leading to an underestimated λ. Updated distributions of Z and λ were produced for the GBR population and corrected obvious error in the demographic parameters for the PNG population. This approach provides opportunity for the inverse matrix approach to be applied more broadly to situations where information on population structure is lacking.