bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of AMPK inhibits TGF-β1-induced airway smooth muscle cells proliferation and its potential mechanisms
Authors: Pan Yilin , Liu Lu , Li Shaojun , Wang Ke , Ke Rui , Shi Wenhua , Wang Jian , Yan Xin , Zhang Qianqian , Wang Qingting , Chai Limin , Xie Xinming , Li Manxiang 
Published: February 2018

AbstractThe aims of the present study were to examine signaling mechanisms underlying transforming growth factor β1 (TGF-β1)-induced airway smooth muscle cells (ASMCs) proliferation and to determine the effect of adenosine monophosphate-activated protein kinase (AMPK) activation on TGF-β1-induced ASMCs proliferation and its potential mechanisms. TGF-β1 reduced microRNA-206 (miR-206) level by activating Smad2/3, and this in turn up-regulated histone deacetylase 4 (HDAC4) and consequently increased cyclin D1 protein leading to ASMCs proliferation. Prior incubation of ASMCs with metformin induced AMPK activation and blocked TGF-β1-induced cell proliferation. Activation of AMPK slightly attenuated TGF-β1-induced miR-206 suppression, but dramatically suppressed TGF-β1-caused HDAC4 up-expression and significantly increased HDAC4 phosphorylation finally leading to reduction of up-regulated cyclin D1 protein expression. Our study suggests that activation of AMPK modulates miR-206/HDAC4/cyclin D1 signaling pathway, particularly targeting on HDAC4, to suppress ASMCs proliferation and therefore has a potential value in the prevention and treatment of asthma by alleviating airway remodeling.
A rice class-XIV kinesin enters the nucleus in response to cold
Authors: Xu Xiaolu , Walter Wilhelm J. , Liu Qiong , Machens Isabel , Nick Peter 
Published: February 2018

AbstractHigher plants possess a large number of kinesins, but lack the minus-end directed dynein motors. However, the kinesin class XIV has strongly expanded, and minus-end directed motors from this class may have taken over functions of cytoplasmic dyneins. In this study, we address the functional aspects of a novel rice homologue of the Arabidopsis class-XIV kinesins ATK1 and ATK5. Since a loss-of-function rice mutant of this kinesin is not viable, the function was studied in tobacco BY-2 as heterologous system. OsDLK-GFP stably expressed in BY-2 cells decorates cortical microtubules, but also can shift into the nucleus of interphase cells. Because of this peculiar localisation, we coined the name Dual Localisation Kinesin (DLK). The nuclear import of this protein is strongly and reversibly promoted in response to cold. During mitosis, OsDLK is repartitioned between spindle and phragmoplast. Motility assays in vitro using show that OsDLK can convey mutual sliding of microtubules and moves at a velocity comparable to other class-XIV kinesins. When tobacco cells overexpressing OsDLK are synchronised, they exhibit a delayed entry into metaphase, while the later phases of mitosis are accelerated. The data are discussed in relation to additional functions of this kinesin type, beyond their transport along microtubules.
A comparative analysis of surface and bulk contributions to second-harmonic generation in centrosymmetric nanoparticles
Authors: Timbrell Daniel , You Jian Wei , Kivshar Yuri S. , Panoiu Nicolae C. 
Published: February 2018

AbstractSecond-harmonic generation (SHG) from nanoparticles made of centrosymmetric materials provides an effective tool to characterize many important properties of photonic structures at the subwavelength scale. Here we study the relative contribution of surface and bulk effects to SHG for plasmonic and dielectric nanostructures made of centrosymmetric materials in both dispersive and non-dispersive regimes. Our calculations of the far-fields generated by the nonlinear surface and bulk currents reveal that the size of the nanoparticle strongly influences the amount and relative contributions of the surface and bulk SHG effects. Importantly, our study reveals that, whereas for plasmonic nanoparticles the surface contribution is always dominant, the bulk and surface SHG effects can become comparable for dielectric nanoparticles, and thus they both should be taken into account when analyzing nonlinear optical properties of all-dielectric nanostructures.
Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition
Authors: Gonzales Gerard Bryan , De Saeger Sarah 
Published: February 2018

AbstractIn this paper, the stability of the plasma metabolome at −20 °C for up to 30 days was evaluated using liquid chromatography-high resolution mass spectrometric metabolomics analysis. To follow the time-series deterioration of the plasma metabolome, the use of an elastic net regularized regression model for the prediction of storage time at −20 °C based on the plasma metabolomic profile, and the selection and ranking of metabolites with high temporal changes was demonstrated using the glmnet package in R. Out of 1229 (positive mode) and 1483 (negative mode) metabolite features, the elastic net model extracted 32 metabolites of interest in both positive and negative modes. L-gamma-glutamyl-L-(iso)leucine (tentative identification) was found to have the highest time-dependent change and significantly increased proportionally to the storage time of plasma at −20 °C (R2 = 0.6378 [positive mode], R2 = 0.7893 [negative mode], p-value < 0.00001). Based on the temporal profiles of the extracted metabolites by the model, results show only minimal deterioration of the plasma metabolome at −20 °C up to 1 month. However, majority of the changes appeared at around 12–15 days of storage. This allows scientists to better plan logistics and storage strategies for samples obtained from low-resource settings, where −80 °C storage is not guaranteed.
Inhibition of Heat Shock proteins HSP90 and HSP70 induce oxidative stress, suppressing cotton fiber development
Authors: Sable Anshulika , Rai Krishan M. , Choudhary Amit , Yadav Vikash K. , Agarwal Sudhir K. , Sawant Samir V. 
Published: February 2018

AbstractCotton fiber is a specialized unicellular structure useful for the study of cellular differentiation and development. Heat shock proteins (HSPs) have been shown to be involved in various developmental processes. Microarray data analysis of five Gossypium hirsutum genotypes revealed high transcript levels of GhHSP90 and GhHSP70 genes at different stages of fiber development, indicating their importance in the process. Further, we identified 26 and 55 members of HSP90 and HSP70 gene families in G. hirsutum. The treatment of specific inhibitors novobiocin (Nov; HSP90) and pifithrin/2-phenylethynesulfonamide (Pif; HSP70) in in-vitro cultured ovules resulted in a fewer number of fiber initials and retardation in fiber elongation. The molecular chaperone assay using bacterially expressed recombinant GhHSP90-7 and GhHSP70-8 proteins further confirmed the specificity of inhibitors. HSP inhibition disturbs the H2O2 balance that leads to the generation of oxidative stress, which consequently results in autophagy in the epidermal layer of the cotton ovule. Transmission electron microscopy (TEM) of inhibitor-treated ovule also corroborates autophagosome formation along with disrupted mitochondrial cristae. The perturbations in transcript profile of HSP inhibited ovules show differential regulation of different stress and fiber development-related genes and pathways. Altogether, our results indicate that HSP90 and HSP70 families play a crucial role in cotton fiber differentiation and development by maintaining cellular homeostasis.
Normalization of cell associated antiretroviral drug concentrations with a novel RPP30 droplet digital PCR assay
Authors: Dyavar Shetty Ravi , Ye Zhen , Byrareddy Siddappa N. , Scarsi Kimberly K. , Winchester Lee C. , Weinhold Jonathan A. , Fletcher Courtney V. , Podany Anthony T. 
Published: February 2018

AbstractQuantification of antiretroviral (ARV) drug concentrations in peripheral blood mononuclear cells (PBMCs) and tissue isolated mononuclear cells (TIMCs) from lymph node (LNMC) and rectum (RMC) is an important measure of bio-distribution. Normalization of drug concentrations is critical to represent tissue drug concentrations and to analyze both intra-individual and inter-individual variability in drug distribution. However, a molecular method to normalize intracellular drug concentrations in PBMCs and TIMCs methanol extracts is currently unavailable. In this study, a novel droplet digital PCR (ddPCR) assay was designed to amplify RPP30 gene sequence conserved in human and non-human primates (NHP). Genomic DNA (gDNA) isolated from 70 percent methanol embedded PBMCs and TIMCs was used as ddPCR template to quantitate precise RPP30 copies to derive cell counts. The novel molecular method quantitated RPP30 copies in human and rhesus macaque gDNA templates with greater accuracy and precision than qPCR. RPP30 ddPCR derived cell counts are strongly correlated with automated cytometer based cell counts in PBMC (R = 0.90, p = 0.001 and n = 20); LNMC (R = 0.85 p = 0.0001 and n = 22) and RMC (R = 0.92, p = 0.0001 and n = 20) and achieved comparable normalized drug concentrations. Therefore, the RPP30 ddPCR assay is an important normalization method in drug bio-distribution and pharmacokinetic studies in humans and NHPs.
Targeting Ligand Specificity Linked to Tumor Tissue Topological Heterogeneity via Single-Cell Micro-Pharmacological Modeling
Authors: Karolak Aleksandra , Estrella Veronica C. , Huynh Amanda S. , Chen Tingan , Vagner Josef , Morse David L. , Rejniak Katarzyna A. 
Published: February 2018

AbstractTargeted therapy has held promise to be a successful anticancer treatment due to its specificity towards tumor cells that express the target receptors. However, not all targeting drugs used in the clinic are equally effective in tumor eradication. To examine which biochemical and biophysical properties of targeted agents are pivotal for their effective distribution inside the tumor and their efficient cellular uptake, we combine mathematical micro-pharmacological modeling with in vivo imaging of targeted human xenograft tumors in SCID mice. The mathematical model calibrated to experimental data was used to explore properties of the targeting ligand (diffusion and affinity) and ligand release schemes (rates and concentrations) with a goal to identify the properties of cells and ligands that enable high receptor saturation. By accounting for heterogeneities typical of in vivo tumors, our model was able to identify cell- and tissue-level barriers to efficient drug uptake. This work provides a base for utilizing experimentally measurable properties of a ligand-targeted agent and patient-specific attributes of the tumor tissue to support the development of novel targeted imaging agents and for improvement in their delivery to individual tumor cells.
Human Epicardial Adipose Tissue cTGF Expression is an Independent Risk Factor for Atrial Fibrillation and Highly Associated with Atrial Fibrosis
Authors: Wang Qing , Xi Wang , Yin Liang , Wang Jing , Shen Hua , Gao Yang , Min Jie , Zhang Yufeng , Wang Zhinong 
Published: February 2018

AbstractEpicardial adipose tissue (EAT) is associated with the incidence, perpetuation, and recurrence of atrial fibrillation (AF), with elusive underlying mechanisms. We analyzed adipokine expression in samples from 20 patients with sinus rhythm (SR) and 16 with AF. Quantitative real-time PCR showed that connective tissue growth factor (cTGF) expression was significantly higher in EAT than in subcutaneous adipose tissue (SAT) or paracardial adipose tissue (PAT) from patients with AF, and in EAT from patients with SR (P < 0.001). Galectin-3 expression was significantly higher in EAT than in SAT or PAT (P < 0.001), with no significant differences between patients with AF and SR (P > 0.05). Leptin and vaspin expression were lower in EAT than in PAT (P < 0.001). Trichrome staining showed that the fibrosis was much more severe in patients with AF than SR (P < 0.001). We found a linear relationship between cTGF mRNA expression level and collagen volume fraction (y = 1.471x + 27.330, P < 0.001), and logistic regression showed that cTGF level was an independent risk factor for AF (OR 2.369, P = 0.027). In conclusion, highly expressed in EAT, cTGF is associated with atrial fibrosis, and can be an important risk factor for AF.
Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model
Authors: Wang Fuyuan , Meng Jingjing , Zhang Li , Johnson Timothy , Chen Chi , Roy Sabita 
Published: February 2018

AbstractOpioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo. Morphine-induced gut microbial dysbiosis exhibited distinct characteristic signatures, including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance and significant impairment in bile acids and morphine-3-glucuronide/morphine biotransformation in the gut. Moreover, expansion of Enterococcus faecalis was strongly correlated with gut dysbiosis following morphine treatment, and alterations in deoxycholic acid (DCA) and phosphatidylethanolamines (PEs) were associated with opioid-induced metabolomic changes. Collectively, these results indicate that morphine induced distinct alterations in the gut microbiome and metabolome, contributing to negative consequences associated with opioid use. Therapeutics directed at maintaining microbiome homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
Genome sequencing and analysis of Alcaligenes faecalis subsp. phenolicus MB207
Authors: Basharat Zarrin , Yasmin Azra , He Tongtong , Tong Yigang 
Published: February 2018

AbstractBacteria within the genus Alcaligenes, exhibit diverse properties but remain largely unexplored at genome scale. To shed light on the genome structure, heterogeneity and traits of Alcaligenes species, the genome of a tannery effluent isolated Alcaligenes faecalis subsp. phenolicus MB207 was sequenced and assembled. The genome was compared to the whole genome sequences of genus Alcaligenes present in the National Centre for Biotechnology Information database. Core, pan and species specific gene sequences i.e. singletons were identified. Members of this genus did not portray exceptional genetic heterogeneity or conservation and out of 5,166 protein coding genes from pooled genome dataset, 2429 (47.01%) contributed to the core, 1193 (23.09%) to singletons and 1544 (29.88%) to accessory genome. Secondary metabolite forming apparatus, antibiotic production and resistance was also profiled. Alcaligenes faecalis subsp. phenolicus MB207 genome consisted of a copious amount of bioremediation genes i.e. metal tolerance and xenobiotic degrading genes. This study marks this strain as a prospective eco-friendly bacterium with numerous benefits for the environment related research. Availability of the whole genome sequence heralds an opportunity for researchers to explore enzymes and apparatus for sustainable environmental clean-up as well as important compounds/substance production.
Acute Kidney Injury in Trauma Patients Admitted to Critical Care: Development and Validation of a Diagnostic Prediction Model
Authors: Haines Ryan W. , Lin Shih-Pin , Hewson Russell , Kirwan Christopher J. , Torrance Hew D. , O’Dwyer Michael J. , West Anita , Brohi Karim , Pearse Rupert M. , Zolfaghari Parjam , Prowle John R. 
Published: February 2018

AbstractAcute Kidney Injury (AKI) complicating major trauma is associated with increased mortality and morbidity. Traumatic AKI has specific risk factors and predictable time-course facilitating diagnostic modelling. In a single centre, retrospective observational study we developed risk prediction models for AKI after trauma based on data around intensive care admission. Models predicting AKI were developed using data from 830 patients, using data reduction followed by logistic regression, and were independently validated in a further 564 patients. AKI occurred in 163/830 (19.6%) with 42 (5.1%) receiving renal replacement therapy (RRT). First serum creatinine and phosphate, units of blood transfused in first 24 h, age and Charlson score discriminated need for RRT and AKI early after trauma. For RRT c-statistics were good to excellent: development: 0.92 (0.88–0.96), validation: 0.91 (0.86–0.97). Modelling AKI stage 2–3, c-statistics were also good, development: 0.81 (0.75–0.88) and validation: 0.83 (0.74–0.92). The model predicting AKI stage 1–3 performed moderately, development: c-statistic 0.77 (0.72–0.81), validation: 0.70 (0.64–0.77). Despite good discrimination of need for RRT, positive predictive values (PPV) at the optimal cut-off were only 23.0% (13.7–42.7) in development. However, PPV for the alternative endpoint of RRT and/or death improved to 41.2% (34.8–48.1) highlighting death as a clinically relevant endpoint to RRT.
Influent factors of gestational vitamin D deficiency and its relation to an increased risk of preterm delivery in Chinese population
Authors: Chen Yuan-Hua , Fu Lin , Hao Jia-Hu , Wang Hua , Zhang Cheng , Tao Fang-Biao , Xu De-Xiang 
Published: February 2018

AbstractGestational vitamin D deficiency (VDD) has been linked with adverse pregnant outcomes. To investigate influent factors of gestational VDD and its relation to the incidence of preterm delivery, total 3598 eligible mother-and-singleton-offspring pairs were recruited. For serum 25(OH)D concentration, 941 pregnant women were sufficient, 1260 insufficient, and 1397 deficient. Further analysis showed that VDD was more prevalent in winter than in other seasons. Underweight but not overweight was a risk factor for gestational VDD. Multivitamin use reduced risk of gestational VDD. Interestingly, 8.23% delivered preterm infants among subjects with VDD (adjusted RR: 4.02; 95% CI: 2.33, 6.92) and 3.81% among subjects with gestational vitamin D insufficiency (VDI) (adjusted RR: 2.07; 95% CI: 1.16, 3.71). Moreover, 2.59% delivered early preterm infants among subjects with VDD (adjusted RR: 2.97; 95% CI: 1.41, 6.24) and 0.49% among subjects with VDI (adjusted RR: 0.54; 95% CI: 0.19, 1.51). The incidence of late preterm delivery was 5.64% among subjects with VDD (adjusted RR: 3.90; 95% CI: 2.26, 6.72) and 3.32% among subjects with VDI (adjusted RR: 2.09; 95% CI: 1.17, 3.74). In conclusion, pre-pregnancy BMI, seasonality and multivitamin use are influent factors of gestational vitamin D status. Gestational VDD is associated with an increased risk of preterm delivery in Chinese population.
Magnetic properties and magnetocrystalline anisotropy of Nd2Fe17, Nd2Fe17X3, and related compounds
Authors: Pandey Tribhuwan , Parker David S. 
Published: February 2018

AbstractThe electronic and magnetic properties of Nd2Fe17 and Nd2Fe17X3 (X = C or N) compounds have been calculated using the first-principles density functional calculations. Among these, the nitrogen and carbon interstitial compounds exhibit all of the required properties such as a saturation moment of 1.6 T, Curie temperature of 700–750 K, however easy magnetic axis lies in the planar direction making them less attractive for permanent magnet applications. The calculated magnetocrystalline anisotropy energy is found to be −2.7 MJ/m3 for Nd2Fe17C3 and −4.7 MJ/m3 for Nd2Fe17N3. We further explored the possibility of changing the easy axis direction through La/Ce alloying at Nd site. Although the MAE is found to be smaller in magnitude for all the La/Ce alloys it still maintains planar direction.
Prediabetes and diabetes in a cohort of Qatari women screened for polycystic ovary syndrome
Authors: Dargham Soha R. , Shewehy Abeer El , Dakroury Youssra , Kilpatrick Eric S. , Atkin Stephen L. 
Published: February 2018

AbstractPolycystic ovary syndrome (PCOS) is associated with an increased risk of type 2 diabetes mellitus (T2DM) but its association with prediabetes and T2DM is unknown in Qatar. A cross sectional analysis of 3,017 Qatari subjects from the Qatar Biobank, identified 749 women aged 18–40 years, 720 of whom were assessed by the National Institute for Health (NIH) Guidelines for PCOS. Prediabetes (HbA1c 5.7–6.4% and/or impaired fasting glucose (IFG): fasting plasma glucose (FPG) 100–125 mg/dL (5.6–6.9 mmol/L)), and T2DM (fasting plasma glucose > 125 mg/dL (≥7 mmol/L), and/or HbA1c ≥ 6.5%) were determined. The prevalence of prediabetes was 10.6% and the prevalence of undiagnosed diabetes was found to be 4.0% in the total population. Overall, 12.1% of 720 women had PCOS, of whom FPG and HbA1c were available in 62 women with PCOS: 19.4% had prediabetes and 9.7% had diabetes. An adverse cardiovascular risk profile for IFG women compared to normal women was found. Women with PCOS alone had a similar adverse cardiovascular profile as those with IFG alone and T2DM. Thus, the risk of prediabetes and diabetes is increased in Qatari women with PCOS, with an adverse cardiovascular risk profile similar to that seen in prediabetes and T2DM.
Light Emission from Plasmonic Nanostructures Enhanced with Fluorescent Nanodiamonds
Authors: Zhao Jingyi , Cheng Yuqing , Shen Hongming , Hui Yuen Yung , Wen Te , Chang Huan-Cheng , Gong Qihuang , Lu Guowei 
Published: February 2018

AbstractIn the surface-enhanced fluorescence (SEF) process, it is well known that the plasmonic nanostructure can enhance the light emission of fluorescent emitters. With the help of atomic force microscopy, a hybrid system consisting of a fluorescent nanodiamond and a gold nanoparticle was assembled step-by-step for in situ optical measurements. We demonstrate that fluorescent emitters can also enhance the light emission from gold nanoparticles which is judged through the intrinsic anti-Stokes emission owing to the nanostructures. The light emission intensity, spectral shape, and lifetime of the hybrid system were dependent on the coupling configuration. The interaction between gold nanoparticles and fluorescent emitter was modelled based on the concept of a quantised optical cavity by considering the nanodiamond and the nanoparticle as a two-level energy system and a nanoresonator, respectively. The theoretical calculations reveal that the dielectric antenna effect can enhance the local field felt by the nanoparticle, which contributes more to the light emission enhancement of the nanoparticles rather than the plasmonic coupling effect. The findings reveal that the SEF is a mutually enhancing process. This suggests the hybrid system should be considered as an entity to analyse and optimise surface-enhanced spectroscopy.