bluuebunny/crossref_metadata_2025_split huggingface dataset:
An intact model for quantifying functional selectivity
Authors: Zhu Xiao , Finlay David B. , Glass Michelle , Duffull Stephen B. 
Published: February 2019

AbstractA ligand that acts on a target receptor to activate particular multiple signalling pathways with activity that is distinct from other ligands is termed ligand bias. Quantification of ligand bias is based on applying the operational model to each pathway separately and subsequent calculation of the ligand bias metric (ΔΔlogR). This approach implies independence among different pathways and causes propagation of error in the calculation. Here, we propose a semi-mechanism-based model which allows for receptor selectivity across all the pathways simultaneously (termed the ‘intact operational model’). The power of the intact model for detecting ligand bias was evaluated via stochastic simulation estimation studies. It was also applied to two examples: (1) opposing effects of Gi/Gs signalling of α2-adrenergic receptors and (2) simultaneous measurement of arachidonic acid release and inositol phosphate accumulation following 5-HT2C receptor activation. The intact operational model demonstrated greater power to detect ligand bias in the simulation. In the applications, it provided better precision of estimation and identified biased ligands that were missed by analysis of traditional methods. Issues identified in both examples might lead to different interpretations of the data. The intact operational model may elucidate greater understanding of the underlying mechanisms of functional selectivity.
Chlorin e6-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters as a Theranostic Agent for Dual-Mode Imaging and Photodynamic Therapy
Authors: Amirshaghaghi Ahmad , Yan Lesan , Miller Joann , Daniel Yonathan , Stein Joel M. , Busch Theresa M. , Cheng Zhiliang , Tsourkas Andrew 
Published: February 2019

AbstractPhotodynamic therapy (PDT) is an approved modality for the treatment of various types of maligancies and diseased states. However, most of the available photosensitizers (PS) are highly hydrophobic, which limits their solubility and dispersion in biological fluids and can lead to self-quenching and sub-optimal therapeutic efficacy. In this study, chlorin e6 (Ce6)-coated superparamagnetic iron oxide nanoparticle (SPION) nanoclusters (Ce6-SCs) were prepared via an oil-in-water emulsion. The physical-chemical properties of the Ce6-SCs were systematically evaluated. Dual-mode imaging and PDT was subsequently performed in tumor-bearing mice. Chlorin e6 is capable of solubilizing hydrophobic SPION into stable, water-soluble nanoclusters without the use of any additional amphiphiles or carriers. The method is reproducible and the Ce6-SCs are highly stable under physiological conditions. The Ce6-SCs have an average diameter of 92 nm and low polydispersity (average PDI < 0.2). Encapsulation efficiency of both Ce6 and SPION is ≈100%, and the total Ce6 payload can be as high as 56% of the total weight (Ce6 + Fe). The Ce6-SCs localize within tumors via enhanced permeability and retention and are detectable by magnetic resonance (MR) and optical imaging. With PDT, Ce6-SCs demonstrate high singlet oxygen generation and produce a significant delay in tumor growth in mice.
Home-based Aerobic Exercise and Resistance Training in Peritoneal Dialysis Patients: A Randomized Controlled Trial
Authors: Uchiyama Kiyotaka , Washida Naoki , Morimoto Kohkichi , Muraoka Kaori , Kasai Takahiro , Yamaki Kentaro , Miyashita Kazutoshi , Wakino Shu , Itoh Hiroshi 
Published: February 2019

AbstractPotential effects of aerobic and resistance training in peritoneal dialysis (PD) patients have been partially elucidated. We investigated effects of a home-based exercise program on physical functioning and health-related quality of life (HRQOL) in PD patients. Patients were randomly assigned to exercise (n = 24) and usual care (n = 23) groups. The exercise patients performed aerobic exercise thrice weekly and resistance training twice weekly at home for 12 weeks. The usual care patients received no specific intervention. The distance in incremental shuttle walking test significantly improved in the exercise group compared with the usual care group (P = 0.02). Among the HRQOL subscales assessed using the Kidney Disease Quality of Life-Short Form questionnaire, kidney disease component summary (P = 0.03), physical role functioning (P = 0.01), emotional role functioning (P < 0.01), and role/social component summary (P < 0.01) significantly improved in the exercise group. Moreover, serum albumin was significantly maintained in the exercise group (P = 0.03). There were no reported adverse events associated with the intervention. To our knowledge, this is the first randomized controlled trial to indicate the beneficial effects of a 12-week home-based exercise program exclusively in PD patients.
Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice
Authors: Reijntjes Daniël O. J. , Lee Jeong Han , Park Seojin , Schubert Nick M. A. , van Tuinen Marcel , Vijayakumar Sarath , Jones Timothy A. , Jones Sherri M. , Gratton Michael Anne , Xia Xiao-Ming , Yamoah Ebenezer N. , Pyott Sonja J. 
Published: February 2019

AbstractPotassium (K+) channels shape the response properties of neurons. Although enormous progress has been made to characterize K+ channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and single molecule fluorescent in situ hybridization, we localized expression of transcripts encoding the sodium-activated potassium channels KNa1.1 (SLO2.2/Slack) and KNa1.2 (SLO2.1/Slick) to the primary auditory neurons (spiral ganglion neurons, SGNs). To examine the contribution of these channels to function of the SGNs in vivo, we measured auditory brainstem responses in KNa1.1/1.2 double knockout (DKO) mice. Although auditory brainstem response (wave I) thresholds were not altered, the amplitudes of suprathreshold responses were reduced in DKO mice. This reduction in amplitude occurred despite normal numbers and molecular architecture of the SGNs and their synapses with the inner hair cells. Patch clamp electrophysiology of SGNs isolated from DKO mice displayed altered membrane properties, including reduced action potential thresholds and amplitudes. These findings show that KNa1 channel activity is essential for normal cochlear function and suggest that early forms of hearing loss may result from physiological changes in the activity of the primary auditory neurons.
Imatinib treatments have long-term impact on placentation and embryo survival
Authors: Salem Wael , Li Kailiang , Krapp Christopher , Ingles Sue Ann , Bartolomei Marisa S. , Chung Karine , Paulson Richard J. , Nowak Romana A. , McGinnis Lynda K. 
Published: February 2019

AbstractImatinib is an oral chemotherapeutic used primarily to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). The potential effects of cancer treatments on a patient’s future fertility are a major concern affecting the quality of life for cancer survivors. The effects of imatinib on future fertility are unknown. It is teratogenic. Therefore, patients are advised to stop treatment before pregnancy. Unfortunately, CML and GIST have high rates of recurrence in the absence of the drug, therefore halting imatinib during pregnancy endangers the mother. Possible long-term (post-treatment) effects of imatinib on reproduction have not been studied. We have used a mouse model to examine the effects of imatinib on the placenta and implantation after long-term imatinib exposure. We found significant changes in epigenetic markers of key imprinted genes in the placenta. There was a significant decrease in the labyrinth zone and vasculature of the placenta, which could impact fetal growth later in pregnancy. These effects on placental growth occurred even when imatinib was stopped prior to pregnancy. These results indicate potential long-term effects of imatinib on pregnancy and implantation. A prolonged wash-out period prior to pregnancy or extra monitoring for possible placental insufficiency may be advisable.
Choosing a laser for laser speckle contrast imaging
Authors: Postnov Dmitry D. , Cheng Xiaojun , Erdener Sefik Evren , Boas David A. 
Published: February 2019

AbstractThe use of laser speckle contrast imaging (LSCI) has expanded rapidly for characterizing the motion of scattering particles. Speckle contrast is related to the dynamics of the scattering particles via a temporal autocorrelation function, but the quality of various elements of the imaging system can adversely affect the quality of the signal recorded by LSCI. While it is known that the laser coherence affects the speckle contrast, it is generally neglected in in vivo LSCI studies and was not thoroughly addressed in a practical matter. In this work, we address the question of how the spectral width of the light source affects the speckle contrast both experimentally and through numerical simulations. We show that commonly used semiconductor laser diodes have a larger than desired spectral width that results in a significantly reduced speckle contrast compared with ideal narrow band lasers. This results in a reduced signal-to-noise ratio for estimating changes in the motion of scattering particles. We suggest using a volume holographic grating stabilized laser diode or other diodes that have a spectrum of emitted light narrower than ≈1 nm to improve the speckle contrast.
Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice
Authors: Park Yong H. , Snook Joshua D. , Ostrin Edwin J. , Kim Sangbae , Chen Rui , Frankfort Benjamin J. 
Published: February 2019

AbstractElevated intraocular pressure (IOP) is the major risk factor for glaucoma, a sight threatening disease of retinal ganglion cells (RGCs) and their axons. Despite the central importance of IOP, details of the impact of IOP elevation on RGC gene expression remain elusive. We developed a 4-step immunopanning protocol to extract adult mouse RGCs with high fidelity and used it to isolate RGCs from wild type mice exposed to 2 weeks of IOP elevation generated by the microbead model. IOP was elevated to 2 distinct levels which were defined as Mild (IOP increase >1 mmHg and <4 mmHg) and Moderate (IOP increase ≥4 mmHg). RNA sequencing was used to compare the transcriptional environment at each IOP level. Differentially expressed genes were markedly different between the 2 groups, and pathway analysis revealed frequently opposed responses between the IOP levels. These results suggest that the magnitude of IOP elevation has a critical impact on RGC transcriptional changes. Furthermore, it is possible that IOP-based set points exist within RGCs to impact the direction of transcriptional change. It is possible that this improved understanding of changes in RGC gene expression can ultimately lead to novel diagnostics and therapeutics for glaucoma.
Archean crust and metallogenic zones in the Amazonian Craton sensed by satellite gravity data
Authors: Motta J. G. , SOUZA FILHO C. R. de , Carranza E. J. M. , Braitenberg C. 
Published: February 2019

AbstractThe formation of ore deposits has been extensively studied from a shallow crust perspective. In contrast, the association of mineral systems with deep crustal structure of their host terranes remains relatively undisclosed, and there is evidence that processes throughout the lithosphere are coupled for their evolution. The current debate centers on the control of the regional deep crustal architecture in focusing and transferring fluids between geochemical reservoirs. Defining such architecture is not unequivocal, and involves combining indirect information in order to constrain its physical properties and evolution. Herein, based on evidence from satellite gravity, constrained by airborne potential field data (gravity and magnetics), we provide an example on how the lithosphere geometry controlled the location of copper and gold systems in the world-class Archean Carajás Mineral Province (Amazonian Craton, South America). Validation with information from passive seismic (wave speeds, crustal and lithospheric thickness) and geochronologic data (model, crystallization ages, and Neodymium isotope ratio determinations) portrays a significantly enlarged, poly-phase, Archean crust that exerted geometric control on the location of the mineral systems within and adjacent to the province during tectonic quiescence and switches. This new geologic scenario impacts the understanding of the Amazonian Craton. Synergy between multi-source data, as experimented here, can provide robust models efficiently and, conceivably, help to unveil similar terrains elsewhere.
Effects of a Saccharomyces cerevisiae fermentation product on liver abscesses, fecal microbiome, and resistome in feedlot cattle raised without antibiotics
Authors: Huebner Katherine L. , Martin Jennifer N. , Weissend Carla J. , Holzer Katlyn L. , Parker Jennifer K. , Lakin Steven M. , Doster Enrique , Weinroth Margaret D. , Abdo Zaid , Woerner Dale R. , Metcalf Jessica L. , Geornaras Ifigenia , Bryant Tony C. , Morley Paul S. , Belk Keith E. 
Published: February 2019

AbstractLiver abscesses in feedlot cattle form secondary to high concentrate feeds and rumen acidosis. Antimicrobial drugs are commonly included in cattle feed for prevention of liver abscesses, but concerns regarding antimicrobial resistance have increased the need for alternative treatments. A block randomized clinical trial was conducted to evaluate the effects of aSaccharomyces cerevisiaefermentation product (SCFP) on liver abscesses, fecal microbiomes, and resistomes in cattle raised without antibiotics in a Colorado feedlot. At enrollment, steers (n = 4,689) were sorted, by weight and source, into 2 pens comprising a block (n = 14 blocks, 28 pens); pens were randomly allocated to either the control group or the treatment group, where the diet was supplemented with SCFP. Prior to harvest, composited feces were collected for characterization of the microbiome and resistome using 16S rRNA gene and shotgun sequencing. At harvest, liver abscess severity was quantified for individual cattle. There were no statistical differences detected by treatment group in animal health, liver abscess prevalence or severity. Organisms classified to phylum, Elusimicrobia were more abundant in the feces of treated cattle, however, there were no differences in the resistome by treatment group. Both microbiome and resistome varied significantly among enrollment blocks.
Basal forebrain somatostatin cells differentially regulate local gamma oscillations and functionally segregate motor and cognitive circuits
Authors: Espinosa Nelson , Alonso Alejandra , Lara-Vasquez Ariel , Fuentealba Pablo 
Published: February 2019

AbstractThe basal forebrain delivers extensive axonal projections to the cortical mantle regulating brain states and cognitive processing. Recent evidence has established the basal forebrain as a subcortical node of the default mode network that directionally influences cortical dynamics trough gamma oscillations, yet their synaptic origin has not been established. Here, we used optogenetic stimulation and in vivo recordings of transgenic mice to show that somatostatin neurons exert an anatomically specialized role in the coordination of subcortical gamma oscillations of the rostral basal forebrain. Indeed, the spike timing of somatostatin cells was tightly correlated with gamma oscillations in the ventral pallidum, but not in the medial septum. Consequently, optogenetic inactivation of somatostatin neurons selectively disrupted the amplitude and coupling of gamma oscillations only in the ventral pallidum. Moreover, photosupression of somatostatin cells produced specific behavioral interferences, with the ventral pallidum regulating locomotor speed and the medial septum modulating spatial working memory. Altogether, these data suggest that basal forebrain somatostatin cells can selectively synchronize local neuronal networks in the gamma band directly impinging on cortical dynamics and behavioral performance. This further supports the role of the basal forebrain as a subcortical switch commanding transitions between internally and externally oriented brain states.
A Systematic Review and Meta-Analysis Comparing Programmed Intermittent Bolus and Continuous Infusion as the Background Infusion for Parturient-Controlled Epidural Analgesia
Authors: Xu Jiqian , Zhou Jie , Xiao Hairong , Pan Shangwen , Liu Jie , Shang You , Yao Shanglong 
Published: February 2019

AbstractThe programmed intermittent epidural bolus (PIEB) technique offers multiple benefits over continuous epidural infusion (CEI), but controversy still exists when it is used in conjunction with a parturient-controlled epidural analgesia (PCEA) regimen. A systematic review and meta-analysis was thus conducted using the Medline, EMBASE, CENTRAL and Web of Science databases with the aim of identifying those randomized controlled trials (RCTs) that performed a comparison between PIEB and CEI in healthy parturients using a PCEA regimen with regard to the duration of labor, labor pain, anesthesia interventions, maternal satisfaction and main side effects. The data were analyzed using a random-effects model. Eleven eligible trials were included, in which 717 participants were allocated to the PIEB + PCEA group and 650 patients were allocated to the CEI + PCEA group. The rate of instrumental delivery, incidence of breakthrough pain, PCEA usage rates and local anesthetic usage were significantly reduced, the labor duration was statistically shorter, and the maternal satisfaction score was significantly improved in the PIEB + PCEA group compared with that in the CEI + PCEA group. There were no differences in the side effects between the two groups. The results of the present study suggest that the PIEB technique in conjunction with the PCEA regimen was more advantageous than CEI + PCEA, but additional studies should be conducted to consistently demonstrate an improvement in the maternal and fetal obstetric outcomes.
Socioeconomic disparity in prefrontal development during early childhood
Authors: Moriguchi Yusuke , Shinohara Ikuko 
Published: February 2019

AbstractSocioeconomic status (SES) has a powerful influence on cognitive, social and brain development. Children from low-SES backgrounds show poor executive function (EF). However, it is unclear if there is a SES-dependent disparity in functional brain development. The present study examined whether the SES of preschool children (N = 93) is associated with prefrontal activation during cognitive shifting tasks as measured by near-infrared spectroscopy. Low-SES children did not show activation in lateral prefrontal regions during the tasks, whereas middle- and high-SES children showed prefrontal activations, although no differences were found in terms of behavioural performance. These results suggest that SES can affect the functional development of the prefrontal regions. In this study, we discuss the practical implications of the results.
A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma
Authors: Zuo Shuguang , Zhang Xinhong , Wang Liping 
Published: February 2019

AbstractGlioblastoma (GBM) is an aggressive tumor of the central nervous system that has poor prognosis despite extensive therapy. Therefore, it is essential to identify a gene expression-based signature for predicting GBM prognosis. The RNA sequencing data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were employed in our study. The univariate and multivariate regression models were utilized to assess the relative contribution of each gene to survival prediction in both cohorts, and the common genes in two cohorts were identified as a final prognostic model. A prognostic risk score was calculated based on the prognostic gene signature. This prognostic signature stratified the patients into the low- and high-risk groups. Multivariate regression and stratification analyses were implemented to determine whether the gene signature was an independent prognostic factor. We identified a 6-gene signature through univariate and multivariate regression models. This prognostic signature stratified the patients into the low- and high-risk groups, implying improved and poor outcomes respectively. Multivariate regression and stratification analyses demonstrated that the predictive value of the 6-gene signature was independent of other clinical factors. This study highlights the significant implications of having a gene signature as a prognostic predictor in GBM, and its potential application in personalized therapy.
New alleles for chlorophyll content and stay-green traits revealed by a genome wide association study in rice (Oryza sativa)
Authors: Zhao Yan , Qiang Chenggen , Wang Xueqiang , Chen Yanfa , Deng Jinqiang , Jiang Conghui , Sun Xingming , Chen Haiyang , Li Jin , Piao Weilan , Zhu Xiaoyang , Zhang Zhanying , Zhang Hongliang , Li Zichao , Li Jinjie 
Published: February 2019

AbstractHigher chlorophyll content (CC) and strong stay-green (SG) traits are conducive for improvement of photosynthetic efficiency in plants. Exploration of natural elite alleles for CC and SG, and highly resolved gene haplotypes are beneficial to rational design of breeding for high-photosynthetic efficiency. Phenotypic analysis of 368 rice accessions showed no significant correlation between CC and SG, and higher CC and stronger SG in japonica than in indica. Genome-wide association studies of six indices for CC and SG identified a large number of association signals, among which 14 were identified as pleiotropic regions for CC and SG. Twenty-five known genes and pleiotropic candidate gene OsSG1 accounted for natural variation in CC and SG. Further analysis indicated that 20 large-effect, non-synonymous SNPs within six known genes around GWAS signals and three SNPs in the promoter of OsSG1 could be functional causing significant phenotypic differences between alleles. Superior haplotypes were identified based on these potentially functional SNPs. Population analyses of 368 cultivated accessions and 446 wild accessions based on SNPs within genes for CC and SG suggested that these genes had been subjected to strong positive selection in japonica in the process of spreading from its subtropical origin to the North China temperate zone. Our studies point to important genes that account for natural variation and provide superior haplotypes of possible functional SNPs that will be beneficial in breeding for high-photosynthetic efficiency in rice.
Oxygen conduction mechanism in Ca3Fe2Ge3O12 garnet-type oxide
Authors: Lee Joohwi , Ohba Nobuko , Asahi Ryoji 
Published: February 2019

AbstractWe investigate the oxygen conduction mechanism in a garnet-type oxide, Ca3Fe2Ge3O12, for the first time in detail by first-principle calculations. The nudged elastic band results confirm that this oxide has a lower migration barrier energy (0.45 eV) for an oxygen interstitial (Oi) with the kick-out mechanism than that (0.76 eV) for an oxygen vacancy. The migration paths for Oi are delocalized and connected to the neighboring cells in three-dimensional space. This oxide does not have a very low formation energy of Oi when the Fermi level is near the lowest unoccupied molecular orbital at a high temperature, which implies the possibility of electron doping by high-valence cations. These theoretical results suggest that the doping of Ca3Fe2Ge3O12 for generation of excess Oi provides a good oxygen-ion conductivity, along with the electronic conductivity.