bluuebunny/crossref_metadata_2025_split huggingface dataset:
Palbociclib has antitumour effects on Pten‐deficient endometrial neoplasias
Authors: Dosil Maria Alba , Mirantes Cristina , Eritja Núria , Felip Isidre , Navaridas Raúl , Gatius Sònia , Santacana Maria , Colàs Eva , Moiola Cristian , Schoenenberger Joan Antoni , Encinas Mario , Garí Eloi , Matias‐Guiu Xavier , Dolcet Xavier 
Published: March 2017

AbstractPTEN is one of the most frequently mutated genes in human cancers. The frequency of PTEN alterations is particularly high in endometrial carcinomas. Loss of PTEN leads to dysregulation of cell division, and promotes the accumulation of cell cycle complexes such as cyclin D1–CDK4/6, which is an important feature of the tumour phenotype. Cell cycle proteins have been presented as key targets in the treatment of the pathogenesis of cancer, and several CDK inhibitors have been developed as a strategy to generate new anticancer drugs. Palbociclib (PD‐332991) specifically inhibits CDK4/6, and it has been approved for use in metastatic breast cancer in combination with letrazole. Here, we used a tamoxifen‐inducible Pten knockout mouse model to assess the antitumour effects of cyclin D1 knockout and CDK4/6 inhibition by palbociclib on endometrial tumours. Interestingly, both cyclin D1 deficiency and palbociclib treatment triggered shrinkage of endometrial neoplasias. In addition, palbociclib treatment significantly increased the survival of Pten‐deficient mice, and, as expected, had a general effect in reducing tumour cell proliferation. To further analyse the effects of palbociclib on endometrial carcinoma, we established subcutaneous tumours with human endometrial cancer cell lines and primary endometrial cancer xenografts, which allowed us to provide more translational and predictive data. To date, this is the first preclinical study evaluating the response to CDK4/6 inhibition in endometrial malignancies driven by PTEN deficiency, and it reveals an important role of cyclin D–CDK4/6 activity in their development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Microinsertions in PRKACA cause activation of the protein kinase A pathway in cardiac myxoma
Authors: Tseng I‐Ching , Huang Wei‐Ju , Jhuang Yu‐Ling , Chang Ya‐Yun , Hsu Hung‐Pin , Jeng Yung‐Ming 
Published: March 2017

AbstractCardiac myxoma is the most common cardiac tumour. Most lesions occur sporadically, but occasional lesions develop in patients with Carney complex, a syndrome characterized by cardiac myxoma, spotty pigmentation, and endocrine overactivity. Two‐thirds of patients with Carney complex harbour germline mutations in PRKAR1A, which encodes the type I regulatory subunit of protein kinase A (PKA). Most studies have not found a mutation in PRKAR1A in sporadic cardiac myxoma cases. Recent studies identified frequent mutations in PRKACA, which encodes the catalytic subunit of PKA, in cortisol‐secreting adrenocortical adenoma cases. To determine whether the PRKACA mutation is involved in the tumourigenesis of cardiac myxoma, we performed Sanger sequencing of 41 specimens of sporadic cardiac myxoma to test for the presence of mutations in the coding regions and intron–exon boundaries of PRKACA. Mutations were identified in four cases (9.7%). In contrast to the point mutations identified in adrenocortical adenoma, all mutations were in‐frame microinsertions of 18–33 bp clustered in exons 7 and 8. The mutated PRKACA proteins lost their ability to bind to PRKAR1A, and thereby lead to constitutive activation of the PKA pathway. Together with previous reports of PRKAR1A mutations in syndromic cardiac myxoma, our study demonstrates the importance of the PKA pathway in the tumourigenesis of cardiac myxoma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The fluorescence intensities ratio is not a reliable parameter for evaluation of protein unfolding transitions
Authors: Žoldák Gabriel , Jancura Daniel , Sedlák Erik 
Published: March 2017

AbstractMonitoring the fluorescence of proteins, particularly the fluorescence of intrinsic tryptophan residues, is a popular method often used in the analysis of unfolding transitions (induced by temperature, chemical denaturant, and pH) in proteins. The tryptophan fluorescence provides several suitable parameters, such as steady‐state fluorescence intensity, apparent quantum yield, mean fluorescence lifetime, position of emission maximum that are often utilized for the observation of the conformational/unfolding transitions of proteins. In addition, the fluorescence intensities ratio at different wavelengths (usually at 330 nm and 350 nm) is becoming an increasingly popular parameter for the evaluation of thermal transitions. We show that, under certain conditions, the use of this parameter for the analysis of unfolding transitions leads to the incorrect determination of thermodynamic parameters characterizing unfolding transitions in proteins (e.g., melting temperature) and, hence, can compromise the hit identification during high‐throughput drug screening campaigns.
Design, synthesis, antiviral bioactivity and three‐dimensional quantitative structure–activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety
Authors: Wu Zengxue , Zhang Jian , Chen Jixiang , Pan Jianke , Zhao Lei , Liu Dengyue , Zhang Awei , Chen Jin , Hu Deyu , Song Baoan 
Published: March 2017

AbstractBACKGROUNDFerulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities.RESULTSBioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC50 values of 162.14, 114.61 and 255.49, 138.81 mg L−1, respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L−1). The values of q2 and r2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities.CONCLUSIONSome of the title compounds demonstrated good antiviral activities. Three‐dimensional quantitative structure–activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry
Finite‐time sliding mode observer for uncertain nonlinear systems based on a tunable algebraic solver
Authors: López Esteban , Botero Héctor 
Published: March 2017

SummaryIn this paper, a finite‐time sliding mode observer for nonlinear systems with unknown inputs is proposed. The observer is based on a method for the solution of time‐varying algebraic equations. This algebraic solver is shown to converge in finite time by means of Lyapunov analysis; furthermore, a way to tune it so that it converges after a user‐defined amount of time is presented. Through the use of this technique and sliding mode differentiators, the state variables and unknown inputs of a class of nonlinear systems, which do not need to be affine in the inputs, can be estimated without the explicit use of state transformations. Both the algebraic solver and the proposed observer are illustrated through simulation examples. Copyright © 2017 John Wiley & Sons, Ltd.
Theoretical Studies for Switching Regioselectivity in Ruthenium Hydride‐Catalyzed Alkyne Hydroacylation
Authors: Wang Fen , Meng Qingxi 
Published: March 2017

AbstractDensity functional theory (DFT) was used to elucidate and explore ruthenium hydride‐catalyzed intermolecular pent‐2‐yne hydroacylation with three phosphine ligands (PMe3, PPh3, ferrocene‐based Josiphos L3). Ruthenium‐PMe3‐catalyzed intermolecular pent‐2‐yne hydroacylation had five plausible pathways producing five possible products (β,γ‐unsaturated ketones p1, p2, p3, and α,β‐unsaturated ketones p4, p5), and the α‐Et‐β,γ‐unsaturated ketone p1 was predicted theoretically to be dominant. Three steps (hydrogen migration, nucleophilic reaction, β‐hydrogen elimination) were the rate‐determining step for this pathway affording α‐Et‐β,γ‐unsaturated ketone p1. In ruthenium‐PPh3‐catalyzed pent‐2‐yne hydroacylation, the rate‐determining step was the β‐hydrogen elimination. In ruthenium‐L3‐catalyzed pent‐2‐yne hydroacylation, the rate‐determining step was also the β‐hydrogen elimination. Furthermore, the similarities and differences of three phosphine ligands were studied and indicated. All results were consistent with Dong's experiments.
Interaction Behavior between Active Hydrogen Bond Donor‐Acceptors as a Binding Decoration for Anion Recognition: Experimental Observation and Theoretical Validation
Authors: Karar Monaj , Paul Suvendu , Mallick Arabinda , Majumdar Tapas 
Published: March 2017

AbstractInteractions of Harmine (HM), as hydrogen bond donor with different anions as hydrogen bond acceptors were studied using spectroscopic and computational techniques. Significant gradual changes in absorption and emission spectra were observed upon addition of fluoride anions with selectivity. Wide‐ranging theoretical calculations in association with the 1H NMR titration in CDCl3 medium were performed to establish the binding decoration of HM with fluoride ion. Interaction energies, bond length variation, NBO charge transfer, NMR response, MEP 3D surface & 2D contour plot, UV‐Vis spectral simulation, HOMO‐LUMO energy gaps and potential energy curves (PECs) were calculated theoretically employing DFT method for ground state (S0) and TD‐DFT method for first singlet excited electronic state (S1) in ACN. Calculations revealed the proton transfer as ESPT mechanism [extent of proton transfer in S0 (58 %) and S1 (87 %)] behind the molecular interaction and spectral responses. We believe such a fluoride selective sensor like HM may find application to detect and control fluoride content in different commodity products.
Trajectories of ageing well among older Australians: a 16-year longitudinal study
Authors: BROWNING COLETTE J. , ENTICOTT JOANNE C. , THOMAS SHANE A. , KENDIG HAL 
Published: March 2017

ABSTRACTIn this study we used individual differences concepts and analyses to examine whether older people achieve different ageing-well states universally or whether there are identifiable key groups that achieve them to different extents. The data used in the modelling were from a prospective 16-year longitudinal study of 1,000 older Australians. We examined predictors of trajectories for ageing well using self-rated health, psychological wellbeing and independence in daily living as joint indicators of ageing well in people aged over 65 years at baseline. We used group-trajectory modelling and multivariate regression to identify characteristics predicting ‘ageing well’. The results showed three distinct and sizeable ageing trajectory groups: (a) ‘stable-good ageing well’ (classified as ageing well in all longitudinal study waves; which was achieved by 30.2% of women and 28.0% of men); (b) ‘initially ageing well then deteriorating’ (50.5% women and 47.6% men); and (c) ‘stable-poor’ (not ageing well in any wave; 19.3% women and 24.4% men). Significant gender differences were found in membership in different ageing-well states. In the stable-poor groups there were 103/533 females which was significantly lower than 114/467 men (z-statistic = −2.6, p = 0.005); women had a ‘zero’ probability of progressing to a better ageing-well classification in later years, whilst males had a one-in-five probability of actually improving. Robust final state outcome predictors at baseline were lower age and fewer medical conditions for both genders; restful sleep and Australian-born for women; and good nutrition, decreased strain, non-smoker and good social support for men. These results support that ageing-well trajectories are influenced by modifiable factors. Findings will assist better targeting of health-promoting activities for older people.
Frugivory and seed dispersal effectiveness in twoMiconia(Melastomataceae) species from ferruginouscampo rupestre
Authors: Santos Alessandra M. O. , Jacobi Claudia M. , Silveira Fernando A. O. 
Published: March 2017

AbstractSeed dispersal effectiveness (SDE) is a useful framework to explore the evolutionary and ecological consequences of seed dispersal to plant fitness. However, SDE is poorly studied in tropical open grasslands. Here, we studied both quantitative and qualitative components of SDE in two species ofMiconia(Melastomataceae) from ferruginouscampo rupestre, a vegetation highly threatened by mining activities. We determined fruit traits and fruit availability and found that fruits of both species are produced in times of resource scarcity at the study site. Based on the number of visits and the number of fruits removed per visit, we calculated the quantitative component of SDE for both species. Finally, we explored the qualitative component of SDE by means of a controlled experiment that simulated the effects of gut passage on seed germination. Bird species differed strongly in the quantitative component of SDE. Gut passage did not affect germination compared with hand-extracted seeds, except for a minor negative effect on germination time inM. pepericarpa.However, seeds within intact fruits showed lower germination percentages compared with hand-extracted seeds. Our data indicate thatMiconiaspecies from ferruginouscampo rupestreare visited by a diverse assemblage of generalist birds that differ in quantitative, but not qualitative, seed dispersal effectiveness. We argue that plantingMiconiaspecies can overcome seed limitation in degraded areas and thus assist ecological restoration after mining abandonment.
Thomas Jefferson, Nature's God, and the Theological Foundations of Natural-Rights Republicanism
Authors: Cooper Kody W. , Dyer Justin Buckley 
Published: March 2017

AbstractWhile the role of theology in Jefferson's political thought and its implications for how we should understand the role of “Nature's God” in grounding natural-rights republicanism are topics of ongoing scholarly interest, scholars have missed important continuities between Jefferson's natural-law theory and that of classical, theistic natural-law. Many scholars who have considered Jefferson in this light have emphasized Jefferson's discontinuity and even subversion of that tradition. In critical dialogue with this vein of scholarship, we argue that Jefferson espouses a creational metaphysics and a natural-law theory of morality that has surprising continuities with classical natural-law. We seek to shed new light on Jefferson's theory of the moral sense and his the earth belongs to the living principle, which we contend encapsulates his theistic understanding of equality and property.
Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface
Authors: Boulay Anne- Cécile , Saubaméa Bruno , Adam Nicolas , Chasseigneaux Stéphanie , Mazaré Noémie , Gilbert Alice , Bahin Mathieu , Bastianelli Leïla , Blugeon Corinne , Perrin Sandrine , Pouch Juliette , Ducos Bertrand , Le Crom Stéphane , Genovesio Auguste , Chrétien Fabrice , Declèves Xavier , Laplanche Jean-Louis , Cohen-Salmon Martine 
Published: March 2017

AbstractAstrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet. Finally, we determined the presence of smooth and rough endoplasmic reticulum and the Golgi apparatus in astrocyte perivascular processes and endfeet, suggesting for local maturation of membrane and secreted proteins. These results demonstrate for the first time that protein synthesis occurs in astrocyte perivascular distal processes that may sustain their structural and functional polarization at the vascular interface.
Device errors in asthma and COPD: systematic literature review and meta-analysis
Authors: Chrystyn Henry , van der Palen Job , Sharma Raj , Barnes Neil , Delafont Bruno , Mahajan Anadi , Thomas Mike 
Published: March 2017

AbstractInhaler device errors are common and may impact the effectiveness of the delivered drug. There is a paucity of up-to-date systematic reviews (SRs) or meta-analyses (MAs) of device errors in asthma and chronic obstructive pulmonary disease (COPD) patients. This SR and MA provides an estimate of overall error rates (both critical and non-critical) by device type and evaluates factors associated with inhaler misuse. The following databases from inception to July 23, 2014 (Embase®, MEDLINE®, MEDLINE® In-Process and CENTRAL) were searched, using predefined search terms. Studies in adult males and females with asthma or COPD, reporting at least one overall or critical error, using metered dose inhalers and dry powder inhalers were included. Random-effect MAs were performed to estimate device error rates and to compare pairs of devices. Overall and critical error rates were high across all devices, ranging from 50–100% and 14–92%, respectively. However, between-study heterogeneity was also generally >90% (I-squared statistic), indicating large variability between studies. A trend towards higher error rates with assessments comprising a larger number of steps was observed; however no consistent pattern was identified. This SR and MA highlights the relatively limited body of evidence assessing device errors and the lack of standardised checklists. There is currently insufficient evidence to determine differences in error rates between different inhaler devices and their impact on clinical outcomes. A key step in improving our knowledge on this topic would be the development of standardised checklists for each device.
Modeling Nosocomial Infections of Methicillin-Resistant Staphylococcus aureus with Environment Contamination*
Authors: Wang Lei , Ruan Shigui 
Published: March 2017

AbstractIn this work, we investigate the role of environmental contamination on the clinical epidemiology of antibiotic-resistant bacteria in hospitals. Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that causes infections in different parts of the body. It is tougher to treat than most strains of Staphylococcus aureus or staph, because it is resistant to some commonly used antibiotics. Both deterministic and stochastic models are constructed to describe the transmission characteristics of MRSA in hospital setting. The deterministic epidemic model includes five compartments: colonized and uncolonized patients, contaminated and uncontaminated health care workers (HCWs), and bacterial load in environment. The basic reproduction number R0 is calculated, and its numerical and sensitivity analysis has been performed to study the asymptotic behavior of the model, and to help identify factors responsible for observed patterns of infections. A stochastic epidemic model with stochastic simulations is also presented to supply a comprehensive analysis of its behavior. Data collected from Beijing Tongren Hospital will be used in the numerical simulations of our model. The results can be used to provide theoretical guidance for designing efficient control measures, such as increasing the hand hygiene compliance of HCWs and disinfection rate of environment, and decreasing the transmission rate between environment and patients and HCWs.
Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction
Authors: Rodriguez-Nunez Ivan , Caluag Tiffany , Kirby Kori , Rudick Charles N. , Dziarski Roman , Gupta Dipika 
Published: March 2017

AbstractGenetics plays a central role in susceptibility to obesity and metabolic diseases. BALB/c mice are known to be resistant to high fat diet (HFD)-induced obesity, however the genetic cause remains unknown. We report that deletion of the innate immunity antibacterial gene Nod2 abolishes this resistance, as Nod2−/− BALB/c mice developed HFD-dependent obesity and hallmark features of metabolic syndrome. Nod2−/− HFD mice developed hyperlipidemia, hyperglycemia, glucose intolerance, increased adiposity, and steatosis, with large lipid droplets in their hepatocytes. These changes were accompanied by increased expression of immune genes in adipose tissue and differential expression of genes for lipid metabolism, signaling, stress, transport, cell cycle, and development in both adipose tissue and liver. Nod2−/− HFD mice exhibited changes in the composition of the gut microbiota and long-term treatment with antibiotics abolished diet-dependent weight gain in Nod2−/− mice, but not in wild type mice. Furthermore, microbiota from Nod2−/− HFD mice transferred sensitivity to weight gain, steatosis, and hyperglycemia to wild type germ free mice. In summary, we have identified a novel role for Nod2 in obesity and demonstrate that Nod2 and Nod2-regulated microbiota protect BALB/c mice from diet-induced obesity and metabolic dysfunction.
Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized Treatments in Multiple Cancer Types
Authors: Shu Yongqian , Wu Xue , Tong Xiaoling , Wang Xiaonan , Chang Zhili , Mao Yu , Chen Xiaofeng , Sun Jing , Wang Zhenxin , Hong Zhuan , Zhu Liangjun , Zhu Chunrong , Chen Jun , Liang Ying , Shao Huawu , Shao Yang W. 
Published: March 2017

AbstractCancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.