bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastid phylogenomics with broad taxon sampling further elucidates the distinct evolutionary origins and timing of secondary green plastids
Authors: Jackson Christopher , Knoll Andrew H. , Chan Cheong Xin , Verbruggen Heroen 
Published: January 2018

AbstractSecondary plastids derived from green algae occur in chlorarachniophytes, photosynthetic euglenophytes, and the dinoflagellate genus Lepidodinium. Recent advances in understanding the origin of these plastids have been made, but analyses suffer from relatively sparse taxon sampling within the green algal groups to which they are related. In this study we aim to derive new insights into the identity of the plastid donors, and when in geological time the independent endosymbiosis events occurred. We use newly sequenced green algal chloroplast genomes from carefully chosen lineages potentially related to chlorarachniophyte and Lepidodinium plastids, combined with recently published chloroplast genomes, to present taxon-rich phylogenetic analyses to further pinpoint plastid origins. We integrate phylogenies with fossil information and relaxed molecular clock analyses. Our results indicate that the chlorarachniophyte plastid may originate from a precusor of siphonous green algae or a closely related lineage, whereas the Lepidodinium plastid originated from a pedinophyte. The euglenophyte plastid putatively originated from a lineage of prasinophytes within the order Pyramimonadales. Our molecular clock analyses narrow in on the likely timing of the secondary endosymbiosis events, suggesting that the event leading to Lepidodinium likely occurred more recently than those leading to the chlorarachniophyte and photosynthetic euglenophyte lineages.
disLocate: tools to rapidly quantify local intermolecular structure to assess two-dimensional order in self-assembled systems
Authors: Bumstead Matt , Liang Kunyu , Hanta Gregory , Hui Lok Shu , Turak Ayse 
Published: January 2018

AbstractOrder classification is particularly important in photonics, optoelectronics, nanotechnology, biology, and biomedicine, as self-assembled and living systems tend to be ordered well but not perfectly. Engineering sets of experimental protocols that can accurately reproduce specific desired patterns can be a challenge when (dis)ordered outcomes look visually similar. Robust comparisons between similar samples, especially with limited data sets, need a finely tuned ensemble of accurate analysis tools. Here we introduce our numerical Mathematica package disLocate, a suite of tools to rapidly quantify the spatial structure of a two-dimensional dispersion of objects. The full range of tools available in disLocate give different insights into the quality and type of order present in a given dispersion, accessing the translational, orientational and entropic order. The utility of this package allows for researchers to extract the variation and confidence range within finite sets of data (single images) using different structure metrics to quantify local variation in disorder. Containing all metrics within one package allows for researchers to easily and rapidly extract many different parameters simultaneously, allowing robust conclusions to be drawn on the order of a given system. Quantifying the experimental trends which produce desired morphologies enables engineering of novel methods to direct self-assembly.
Investigation of 20S-hydroxyvitamin D3 analogs and their 1α-OH derivatives as potent vitamin D receptor agonists with anti-inflammatory activities
Authors: Lin Zongtao , Marepally Srinivasa R. , Goh Emily S. Y. , Cheng Chloe Y. S. , Janjetovic Zorica , Kim Tae-Kang , Miller Duane D. , Postlethwaite Arnold E. , Slominski Andrzej T. , Tuckey Robert C. , Peluso-Iltis Carole , Rochel Natacha , Li Wei 
Published: January 2018

Abstract20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic, suggesting its potential as a lead compound. In this study, side chain modified 20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1α-OH derivatives were synthesized and their metabolism and biological activities tested. 4, 13 and 23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1α-OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than calcitriol, indicating improved catabolic stability. While the parent analogs showed minimal VDR stimulating activity, their 1α-OH derivatives were potent VDR agonists. 4, 5, 14 and 24 significantly upregulated the expression of CYP24A1 at the mRNA level, consistent with their VDR activation abilities and indicating that 1α-hydroxylation is required to produce analogs with strong activity. These analogs have anti-inflammatory activities that are influenced by side chain composition and by 1α-hydroxylation. To understand their molecular interactions with the VDR, 20S(OH)D3, 4 and 33 were co-crystalized with the VDR ligand binding domain, which revealed subtle differences to the calcitriol-bound receptor. This study demonstrates the potential of the 20S(OH)D3 scaffold for the development of novel anti-inflammatory agents.
Cerebral Perfusion Insufficiency and Relationships with Cognitive Deficits in Alzheimer’s Disease: A Multiparametric Neuroimaging Study
Authors: Huang Chi-Wei , Hsu Shih-Wei , Chang Ya-Ting , Huang Shu-Hua , Huang Yung-Cheng , Lee Chen-Chang , Chang Wen-Neng , Lui Chun-Chung , Chen Na-Ching , Chang Chiung-Chih 
Published: January 2018

AbstractMicro- or macro-circulatory insufficiency has a negative impact in patients with Alzheimer’s disease (AD). This study used arterial spin-labeled magnetic resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched controls to investigate how hypoperfusion patterns were associated with gray matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated with regional signals showing significantly lower relative cerebral blood flow (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores served as the outcome measures. Regions with lower PI showed spatial similarities with atrophy in the medial, anterior and superior temporal lobes, posterior cingulate cortex and angular gyrus, while regions showing lower rCBF were localized to the distal branches of posterior cerebral artery territories (posterior parietal and inferior temporal lobe) and watershed areas (angular gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF values in watershed areas correlated with MTC volumes and language composite scores. Precuneus and angular gyrus hypoperfusion were associated with the corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities and cortical atrophy determined the overall perfusion imaging topography and contributed differently to the clinical outcomes.
Young and healthy C57BL/6 J mice performing sprint interval training reveal gender- and site-specific changes to the cortical bone
Authors: Hollinski Robin , Osterberg Anja , Polei Stefan , Lindner Tobias , Cantré Daniel , Mittlmeier Thomas , Vollmar Brigitte , Bruhn Sven , Müller-Hilke Brigitte 
Published: January 2018

AbstractPhysical exercise is considered to impede the bone loss associated with physiological ageing however, a training program that efficiently leads to bone accrual in the healthy does not yet exist. We turned to the C57BL/6 J mouse and designed a sprint interval training for treadmill that was tailored to the individual performance limits. It consisted of four weeks with five training sessions each, followed by another four weeks with three. After completion of the training period, mice were sacrificed and the hind legs were analyzed via µCT and MRI for changes in bone parameters and muscle volume, respectively. Increased performance limits in both sexes confirmed an effect of the treadmill training. However, while male tibiae after eight weeks revealed a significant reduction of cortical bone mass at the distal metaphysis, the cross sectional analysis of female tibiae showed a transient decrease of cortical bone mass after four weeks that was reversed into a significant accrual after eight weeks of training and occurred over the entire length of the tibia. The observed net reduction of female bone mass after four weeks of training is suggestive of a remodelling process which may be delayed in the males.
A new dry eye mouse model produced by exorbital and intraorbital lacrimal gland excision
Authors: Shinomiya Katsuhiko , Ueta Mayumi , Kinoshita Shigeru 
Published: January 2018

AbstractChronic dry eye is an increasingly prevalent condition worldwide, with resulting loss of visual function and quality of life. Relevant, repeatable, and stable animal models of dry eye are still needed. We have developed an improved surgical mouse model for dry eye based on severe aqueous fluid deficiency, by excising both the exorbital and intraorbital lacrimal glands (ELG and ILG, respectively) of mice. After ELG plus ILG excision, dry eye symptoms were evaluated using fluorescein infiltration observation, tear production measurement, and histological evaluation of ocular surface. Tear production in the model mice was significantly decreased compared with the controls. The corneal fluorescein infiltration score of the model mice was also significantly increased compared with the controls. Histological examination revealed significant severe inflammatory changes in the cornea, conjunctiva or meibomian glands of the model mice after surgery. In the observation of LysM-eGFP(+/−) mice tissues, postsurgical infiltration of green fluorescent neutrophils was observed in the ocular surface tissues. We theorize that the inflammatory changes on the ocular surface of this model were induced secondarily by persistent severe tear reduction. The mouse model will be useful for investigations of both pathophysiology as well as new therapies for tear-volume-reduction type dry eye.
Genome-wide association study of paclitaxel and carboplatin disposition in women with epithelial ovarian cancer
Authors: Gao Bo , Lu Yi , Nieuweboer Annemieke J. M. , Xu Hongmei , Beesley Jonathan , Boere Ingrid , de Graan Anne-Joy M. , de Bruijn Peter , Gurney Howard , J. Kennedy Catherine , Chiew Yoke-Eng , Johnatty Sharon E. , Beale Philip , Harrison Michelle , Luccarini Craig , Conroy Don , Mathijssen Ron H. J. , R. Harnett Paul , Balleine Rosemary L. , Chenevix-Trench Georgia , Macgregor Stuart , de Fazio Anna 
Published: January 2018

AbstractIdentifying single nucleotide polymorphisms (SNPs) that influence chemotherapy disposition may help to personalize cancer treatment and limit toxicity. Genome-wide approaches are unbiased, compared with candidate gene studies, but usually require large cohorts. As most chemotherapy is given cyclically multiple blood sampling is required to adequately define drug disposition, limiting patient recruitment. We found that carboplatin and paclitaxel disposition are stable phenotypes in ovarian cancer patients and tested a genome-wide association study (GWAS) design to identify SNPs associated with chemotherapy disposition. We found highly significant SNPs in ABCC2, a known carboplatin transporter, associated with carboplatin clearance (asymptotic P = 5.2 × 106, empirical P = 1.4 × 10−5), indicating biological plausibility. We also identified novel SNPs associated with paclitaxel disposition, including rs17130142 with genome-wide significance (asymptotic P = 2.0 × 10−9, empirical P = 1.3 × 10−7). Although requiring further validation, our work demonstrated that GWAS of chemotherapeutic drug disposition can be effective, even in relatively small cohorts, and can be adopted in drug development and treatment programs.
Genome-wide association mapping and genomic prediction for CBSD resistance in Manihot esculenta
Authors: Kayondo Siraj Ismail , Pino Del Carpio Dunia , Lozano Roberto , Ozimati Alfred , Wolfe Marnin , Baguma Yona , Gracen Vernon , Offei Samuel , Ferguson Morag , Kawuki Robert , Jannink Jean-Luc 
Published: January 2018

AbstractCassava (Manihot esculenta Crantz) is an important security crop that faces severe yield loses due to cassava brown streak disease (CBSD). Motivated by the slow progress of conventional breeding, genetic improvement of cassava is undergoing rapid change due to the implementation of quantitative trait loci mapping, Genome-wide association mapping (GWAS), and genomic selection (GS). In this study, two breeding panels were genotyped for SNP markers using genotyping by sequencing and phenotyped for foliar and CBSD root symptoms at five locations in Uganda. Our GWAS study found two regions associated to CBSD, one on chromosome 4 which co-localizes with a Manihot glaziovii introgression segment and one on chromosome 11, which contains a cluster of nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes. We evaluated the potential of GS to improve CBSD resistance by assessing the accuracy of seven prediction models. Predictive accuracy values varied between CBSD foliar severity traits at 3 months after planting (MAP) (0.27–0.32), 6 MAP (0.40–0.42) and root severity (0.31–0.42). For all traits, Random Forest and reproducing kernel Hilbert spaces regression showed the highest predictive accuracies. Our results provide an insight into the genetics of CBSD resistance to guide CBSD marker-assisted breeding and highlight the potential of GS to improve cassava breeding.
9c11tCLA modulates 11t18:1 and 9t18:1 induced inflammations differently in human umbilical vein endothelial cells
Authors: Li Jing , Hu Sheng-Ben , He Yue-Ming , Zhuo Cheng-Fei , Zhou Ruo-Lin , Chen Fang , Li Hong-yan , Deng Ze-Yuan 
Published: January 2018

AbstractEndothelial inflammation is recognized as the initial stage of a multistep process leading to coronary heart disease (CHD). Recently, the different effects of industrial trans fatty acids (elaidic acid, 9t18:1) and ruminant trans fatty acids (vaccenic acid, 11t18:1) on CHD have been reported in epidemiological and animal studies, however, the mechanism was not fully studied. Therefore, the objective of this study was to explore the underlying mechanism by which 9t18:1 and 11t18:1 affect human umbilical vein endothelial cells (HUVECs) inflammation. We found that 9c11t-CLA modulated the inflammation of HUVECs induced by 9t18:1 and 11t18:1. Fatty acid composition, pro-inflammatory factors, phosphorylation of MAPKs, and the TLR4 level in HUVECs altered by 11t18:1 induction, collectively suggest that the bio-conversion of 11t18:1 to 9c11tCLA might be the cause why 11t18:1 and 9t18:1 have distinct influences on endothelial injuries. It was concluded that it is biosynthesis of 9c11t CLA from11t18:1, and the modulation of TLR4-MAPK pathway by 9c11t CLA, which at least partially account for the slight effect of 11t18:1 on endothelial inflammation.
Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin-A1/EphA2 system in bladder cancer
Authors: Chu Maolin , Zhang Chunying 
Published: January 2018

AbstractAngiogenesis plays an important role in bladder cancer (BCa). The immunosuppressive drug leflunomide has attracted worldwide attention. However, the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a monomeric protein that is a functional form of the ligand. The co-culture supernatants containing sEphrin-A1 caused the internalization and down-regulation of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor xenograft model, as well as in BCa cell and HUVEC co-culture systems, via significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression could partially reverse LEF-induced suppression of angiogenesis and subsequent tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin-A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive therapy.
Vertical Light Sheet Enhanced Side-View Imaging for AFM Cell Mechanics Studies
Authors: Beicker Kellie , O’Brien E. Timothy , Falvo Michael R. , Superfine Richard 
Published: January 2018

AbstractThe ability to measure dynamic structural changes within a cell under applied load is essential for developing more accurate models of cell mechanics and mechanotransduction. Atomic force microscopy is a powerful tool for evaluating cell mechanics, but the dominant applied forces and sample strains are in the vertical direction, perpendicular to the imaging plane of standard fluorescence imaging. Here we report on a combined sideways imaging and vertical light sheet illumination system integrated with AFM. Our system enables high frame rate, low background imaging of subcellular structural dynamics in the vertical plane synchronized with AFM force data. Using our system for cell compression measurements, we correlated stiffening features in the force indentation data with onset of nuclear deformation revealed in the imaging data. In adhesion studies we were able to correlate detailed features in the force data during adhesive release events with strain at the membrane and within the nucleus.
Effect of spin relaxations on the spin mixing conductances for a bilayer structure
Authors: Li D. X. , Shen H. Z. , Liu H. D. , Yi X. X. 
Published: January 2018

AbstractThe spin current can result in a spin-transfer torque in the normal-metal(NM)—ferromagnetic-insulator(FMI) or normal-metal(NM)—ferromagnetic-metal(FMM) bilayer. In the earlier study on this issue, the spin relaxations were ignored or introduced phenomenologically. In this paper, considering the FMM or FMI with spin relaxations described by a non-Hermitian Hamiltonian, we derive an effective spin-transfer torque and an effective spin mixing conductance in the non-Hermitian bilayer. The dependence of the effective spin mixing conductance on the system parameters (such as insulating gap, s-d coupling, and layer thickness) as well as the relations between the real part and the imaginary part of the effective spin mixing conductance are given and discussed. We find that the effective spin mixing conductance can be enhanced in the non-Hermitian system. This provides us with the possibility to enhance the spin mixing conductance.
Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics
Authors: Jones Anya C. , Troy Niamh M. , White Elisha , Hollams Elysia M. , Gout Alexander M. , Ling Kak-Ming , Kicic Anthony , Stick Stephen M. , Sly Peter D. , Holt Patrick G. , Hall Graham L. , Bosco Anthony 
Published: January 2018

AbstractAtopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDMS-wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.
The gait speed advantage of taller stature is lost with age
Authors: Elbaz Alexis , Artaud Fanny , Dugravot Aline , Tzourio Christophe , Singh-Manoux Archana 
Published: January 2018

AbstractTaller individuals walk faster but it is unknown whether this advantage persists at older ages. We examined the cross-sectional/longitudinal associations of height with gait speed (GS) in participants from the Dijon-Three-City cohort study (France) over 11 years. In 4011 participants (65–85 y), we measured usual/fast GS (6 m) up to five times. We examined whether the baseline height-GS association varied with age using linear regression, and whether height influenced GS change using linear mixed models. Taller participants 65 y at baseline walked faster than shorter ones (fast GS difference between top/bottom height quartiles, 0.100 m/s, P < 0.001); this association weakened with age (P-interaction = 0.02), with a 0.012 m/s (P = 0.57) difference at 80 y. Ten-year fast GS decline was 51% greater (P < 0.001) in younger participants in the top height quartile (−0.183 m/s) compared to those in the bottom quartile (−0.121 m/s), leading the GS difference between the two groups to be attenuated by 50% over the follow-up. The height-related difference in fast GS decline was not explained by time-dependent comorbidities or height shrinkage. Analyses for usual GS yielded consistent findings. The height-GS relation is more complex than previously thought, as the height related advantage in GS disappears as persons grow older due to faster decline in taller compared to shorter persons.
Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns
Authors: Lan Tian , Hung Shen-Hsiu , Su Xudong , Wong Samuel W. K. , Tseng Yiider 
Published: January 2018

AbstractVarious subcellular activities, such as protrusion and detachment, compose a cell migration process. The molecular mechanisms of these subcellular activities have been elucidated. However, there is no method that can assess the contributions of these subcellular activities to the global cell migration pattern of a given cell type. Hence, we develop a powerful approach based on CN correlations that quantitatively profiles the cell migration pattern of a given cell type in terms of assembled subcellular activities. In this way, we bridge migration data at the cellular level with underlying molecular mechanisms. The CN correlation profile is found to uniquely and consistently represent the cell migration pattern of each cell type probed. It can clearly reveal the effects of molecular perturbations, such as Y27632 and Cdc42 knockdown on each subcellular migratory activity. As a result, the CN correlation approach serves as a cell dynamic descriptor that can extract comprehensive quantitative data from cell migration movies for integrative biological analyses.