bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced α4 subunit expression in α4+− and α4+−/β2+− nicotinic acetylcholine receptors alters α4β2 subtype up‐regulation following chronic nicotine treatment
Authors: Moretti Milena , Fasoli Francesca , Gotti Cecilia , Marks Michael J 
Published: June 2017

Background and PurposeGenomic analysis has shown many variants in both CHRNA4 and CHRNB2, genes which encode the α4 and β2 subunits of nicotinic ACh receptors (nAChR) respectively. Some variants influence receptor expression, raising the possibility that CHRNA4 variants may affect response to tobacco use in humans. Chronic exposure to nicotine increases expression of nAChRs, particularly α4β2‐nAChRs, in humans and laboratory animals. Here, we have evaluated whether the initial level of receptor expression affects the increase in expression.Experimental ApproachMice differing in expression of α4 and/or β2 nAChR subunits were chronically treated with saline, 0.25, 1.0 or 4.0 mg·kg−1·h−1nicotine. Brain preparations were analysed autoradiographically by [125I]‐epibatidine binding, immunoprecipitation and Western blotting.Key ResultsImmunochemical studies confirmed that most of the [3H]‐epibatidine binding corresponds to α4β2*‐nAChR and that increases in binding correspond to increases in α4 and β2 proteins. Consistent with previous reports, the dose‐dependent increase in nAChR in wild‐type mice following chronic nicotine treatment, measured with any of the methods, reached a maximum. Although receptor expression was reduced by approximately 50% in β2+− mice, the pattern of response to chronic treatment resembled that of wild‐type mice. In contrast, both α4+− and α4+−/β2+− exhibited relatively greater up‐regulation. Consistent with previous reports, α4β2α5‐nAChR did not increase in response to nicotine.Conclusions and ImplicationsThese results indicate that mice with reduced expression of the α4 nAChR subunit have a more robust response to chronic nicotine than mice with normal expression of this subunit.Linked ArticlesThis article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: involvement of circadian clock genes
Authors: Jahanban‐Esfahlan Rana , Mehrzadi Saeed , Reiter Russel J , Seidi Khaled , Majidinia Maryam , Baghi Hossein Bannazadeh , Khatami Nasrin , Yousefi Bahman , Sadeghpour Alireza 
Published: June 2017

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most prevalent joint diseases. A such, they are important causes of pain and disability in a substantial proportion of the human population. A common characteristic of these diseases is the erosion of articular cartilage and consequently joint dysfunction. Melatonin has been proposed as a link between circadian rhythms and joint diseases including RA and OA. This hormone exerts a diversity of regulatory actions through binding to specific receptors and intracellular targets as well as having receptor‐independent actions as a free radical scavenger. Cytoprotective effects of melatonin involve a myriad of prominent receptor‐mediated pathways/molecules associated with inflammation, of which the role of omnipresent NF‐κB signalling is crucial. Likewise, disturbance of circadian timekeeping is closely involved in the aetiology of inflammatory arthritis. Melatonin is shown to stimulate cartilage destruction/regeneration through direct/indirect modulation of the expression of the main circadian clock genes, such as BMAL, CRY and/or DEC2. In the current article, we review the effects of melatonin on RA and OA, focusing on its ability to regulate inflammatory pathways and circadian rhythms. We also review the possible protective effects of melatonin on RA and OA pathogenesis.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc
In vitro‐in silico‐based analysis of the dose‐dependent in vivo oestrogenicity of the soy phytoestrogen genistein in humans
Authors: Boonpawa Rungnapa , Spenkelink Albertus , Punt Ans , Rietjens Ivonne M C M 
Published: June 2017

Background and PurposeThe in vivo oestrogenicity of genistein and its glycoside genistin is still under debate. The present study aimed to develop a physiologically based kinetic (PBK) model that provides insight in dose‐dependent plasma concentrations of genistein aglycone and its metabolites and enables prediction of in vivo oestrogenic effective dose levels of genistein and genistin in humans.Experimental ApproachA PBK model for genistein and genistin in humans was developed based on in vitro metabolic parameters. The model obtained was used to translate in vitro oestrogenic concentration–response curves of genistein to in vivo oestrogenic dose–response curves for intake of genistein and genistin.Key ResultsThe model predicted that genistein‐7‐O‐glucuronide was the major circulating metabolite and that levels of the free aglycone were generally low [0.5–17% of total plasma genistein at oral doses from 0.01 to 50 mg (kg·bw)−1]. The predicted in vivo benchmark dose for 5% response values for oestrogenicity varied between 0.06 and 4.39 mg kg−1 genistein. For genistin, these values were 1.3‐fold higher. These values are in line with reported human data and show that oestrogenic responses can be expected at an Asian dietary and a supplementary intake, while intake resulting from a Western diet may not be effective.Conclusions and ImplicationsThe present study shows how plasma concentrations of genistein and its metabolites and oestrogenic dose levels of genistein in humans can be predicted by combining in vitro oestrogenicity with PBK model‐based reverse dosimetry, eliminating the need for human intervention studies.
SVMDLF: A novel R‐based Web application for prediction of dipeptidyl peptidase 4 inhibitors
Authors: Chandra Sharat , Pandey Jyotsana , Tamrakar Akhilesh K. , Siddiqi Mohammad Imran 
Published: June 2017

Dipeptidyl peptidase 4 (DPP4) is a well‐known target for the antidiabetic drugs. However, currently available DPP4 inhibitor screening assays are costly and labor‐intensive. It is important to create a robust in silico method to predict the activity of DPP4 inhibitor for the new lead finding. Here, we introduce an R‐based Web application SVMDLF (SVM‐based DPP4 Lead Finder) to predict the inhibitor of DPP4, based on support vector machine (SVM) model, predictions of which are confirmed by in vitro biological evaluation. The best model generated by MACCS structure fingerprint gave the Matthews correlation coefficient of 0.87 for the test set and 0.883 for the external test set. We screened Maybridge database consisting approximately 53,000 compounds. For further bioactivity assay, six compounds were shortlisted, and of six hits, three compounds showed significant DPP4 inhibitory activities with IC50 values ranging from 8.01 to 10.73 μm. This application is an OpenCPU server app which is a novel single‐page R‐based Web application for the DPP4 inhibitor prediction. The SVMDLF is freely available and open to all users at http://svmdlf.net/ocpu/library/dlfsvm/www/ and http://www.cdri.res.in/svmdlf/.
Synthesis and biological evaluation of 2‐acylbenzofuranes as novel α‐glucosidase inhibitors with hypoglycemic activity
Authors: Spasov Alexander A. , Babkov Denis A. , Prokhorova Tatyana Yu , Sturova Ekaterina A. , Muleeva Diana R. , Demidov Maxim R. , Osipov Dmitry V. , Osyanin Vitaly A. , Klimochkin Yuri N. 
Published: June 2017

A series of benzofuran derivatives was synthesized as analogues of known natural α‐glucosidase inhibitors. Their activity was evaluated in enzymatic assay and in rat model of diabetes mellitus. Newly identified inhibitors demonstrate significant potency with IC50 values ranging from 6.50 to 722.2 μm, as well as hypoglycemic activity exceeding the reference drug acarbose. Docking simulations provided insight into structure‐activity relationships to direct further development of these novel hypoglycemic agents.
Research priorities for conservation and natural resource management in Oceania's small‐island developing states
Authors: Weeks R. , Adams V. M. 
Published: June 2017

AbstractFor conservation science to effectively inform management, research must focus on creating the scientific knowledge required to solve conservation problems. We identified research questions that, if answered, would increase the effectiveness of conservation and natural resource management practice and policy in Oceania's small‐island developing states. We asked conservation professionals from academia, governmental, and nongovernmental organizations across the region to propose such questions and then identify which were of high priority in an online survey. We compared the high‐priority questions with research questions identified globally and for other regions. Of 270 questions proposed by respondents, 38 were considered high priority, including: What are the highest priority areas for conservation in the face of increasing resource demand and climate change? How should marine protected areas be networked to account for connectivity and climate change? What are the most effective fisheries management policies that contribute to sustainable coral reef fisheries? High‐priority questions related to the particular challenges of undertaking conservation on small‐island developing states and the need for a research agenda that is responsive to the sociocultural context of Oceania. Research priorities for Oceania relative to elsewhere were broadly similar but differed in specific issues relevant to particular conservation contexts. These differences emphasize the importance of involving local practitioners in the identification of research priorities. Priorities were reasonably well aligned among sectoral groups. Only a few questions were widely considered answered, which may indicate a smaller‐than‐expected knowledge‐action gap. We believe these questions can be used to strengthen research collaborations between scientists and practitioners working to further conservation and natural resource management in this region.
A Biologically Plausible Action Selection System for Cognitive Architectures: Implications of Basal Ganglia Anatomy for Learning and Decision‐Making Models
Authors: Stocco Andrea 
Published: June 2017

AbstractSeveral attempts have been made previously to provide a biological grounding for cognitive architectures by relating their components to the computations of specific brain circuits. Often, the architecture's action selection system is identified with the basal ganglia. However, this identification overlooks one of the most important features of the basal ganglia—the existence of a direct and an indirect pathway that compete against each other. This characteristic has important consequences in decision‐making tasks, which are brought to light by Parkinson's disease as well as genetic differences in dopamine receptors. This paper shows that a standard model of action selection in a cognitive architecture (ACT‐R) cannot replicate any of these findings, details an alternative solution that reconciles action selection in the architecture with the physiology of the basal ganglia, and extends the domain of application of cognitive architectures. The implication of this solution for other architectures and existing models are discussed.
Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease
Authors: Yin Tiping , Zhu Zhaoqin , Mei Zhoufang , Feng Jingjing , Zhang Wanju , He Yanchao , Shi Jindong , Qian Ling , Liu Yi , Huang Qihui , Hu Yunwen , Jie Zhijun 
Published: June 2017

AbstractObjectiveTo investigate viral infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Shanghai, and to analyze the clinical characteristics and biomarkers in viral infection.MethodsThis study included all consecutive patients who were admitted for a diagnosis of AECOPD during June 2013 to May 2015. Thirty‐one stable COPD patients and 31 healthy controls were also recruited. Oropharyngeal samples were assessed, PCR for respiratory viruses were performed. Patients were divided into AECOPD virus‐positive (+) group and AECOPD virus‐negative (−) group according to viral detection. Luminex was used to detect the concentrations of inflammatory cytokines in the serum.ResultsA total of 264 patients were included with a mean age of 75 ± 0.5 years. There were 72 patients (27.3%) identified with viral positive, of whom two patients were detected with double viral infections (FluA + FluB and RSVA + HRV, respectively). The rate of viral detection was associated with season, highest in winter. Comparisons of clinical characteristics showed no significant differences between AECOPD virus+ group and AECOPD virus− group. However, serum concentrations of interferon‐inducible protein‐10 (IP‐10) and interferon‐gamma (IFN‐γ) in virus+ AECOPD patients were significantly higher than those in the virus− AECOPD, stable COPD and healthy control groups (P < .05).ConclusionViral infection was an important pathogen in AECOPD patients; the most common viruses included FluA, HRV and FluB. It was very difficult to diagnose the viral infection according to clinical characteristics. The increased of serum IP‐10 and IFN‐γ levels might be value to indicate viral infection in AECOPD.
Weaning attempts, cough strength and albumin are independent risk factors of reintubation in medical patients
Authors: Xiao Meiling , Duan Jun 
Published: June 2017

AbstractBackgroundReintubation is associated with increased hospital mortality. It is necessary to identify risk factors associated with reintubation.MethodsA prospective observational study was performed in a respiratory intensive care unit. Medical patients who successfully completed a spontaneous breathing trial (SBT) were enrolled. Before extubation, age, gender, vital signs, acute physiology and chronic health evaluation II score, SBT attempts, cough peak flow, arterial blood gas tests and albumin were recorded.ResultsWe enrolled 139 patients. Of these, 22 (15.8%) patients experienced reintubation within 72 hours after extubation. SBT attempts (odds ratio [OR] = 1.446, 95% confidence interval [CI]: 1.095‐1.910), cough peak flow (OR = 0.975, 95% CI: 0.956‐0.994) and albumin (OR = 0.847, 95% CI: 0.752‐0.954) were independent risk factors for reintubation. In patients with 1, 2 and ≥3 SBT attempts, reintubation rates were 7.3%, 21.1% and 45.8%, respectively (P < .01). In patients with cough peak flow ≤60, 61‐89 and ≥90 L/min, reintubation rates were 29.4%, 16.7% and 1.9%, respectively (P < .01). In patients with albumin ≤25, 26‐30 and ≥31 g/L, reintubation rates were 32.4%, 11.1% and 9.8%, respectively (P = .01).ConclusionsMultiple SBT attempts, weak cough and low albumin were associated with increased reintubation in medical patients. This study provides information for clinical practitioners in the consideration of patient extubation.
Patterns of glucose‐lowering therapies and neonatal outcomes in the treatment of gestational diabetes in Canada, 2009–2014
Authors: Bowker S. L. , Savu A , Yeung R. O. , Johnson J. A. , Ryan E. A. , Kaul P. 
Published: June 2017

AbstractAimTo examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus.MethodsThis was a large, retrospective, population‐based cohort study of pregnant women with gestational diabetes from Alberta, Canada. We linked data from the Alberta Vital Statistics – Birth database with administrative claims data. Alberta Vital Statistics – Birth data were used to identify births that occurred between 1 January 2009 and 31 December 2014. We used International Classification of Diseases version 9/10 codes to identify women with gestational diabetes, and we excluded women with pre‐existing diabetes.ResultsOur cohort consisted of 16 857 women with gestational diabetes, with a total of 18 761 birth events between 2009 and 2014. Over the study period, the proportion of women with gestational diabetes who were treated with glycaemic control therapies increased from 25.0% to 31.4% (P<0.0001). The number of pregnancies treated with insulin only increased (from 23.6% to 28.3%; P<0.0001), as did the number treated with metformin, +/– insulin (from 1.4% to 3.2%; P<0.0001). Rates of large‐for‐gestational‐age infants were significantly higher among pregnancies treated with insulin only (17%) or metformin (16.5%) than among pregnancies that did not receive any pharmacological treatment (12.8%).ConclusionsOur findings show increasing use of insulin and metformin in women with gestational diabetes. Rates of large‐for‐gestational‐age infants were similar among pregnant women receiving either pharmacological treatment, and higher than among pregnant women who did not receive any pharmacological treatment. Future research should explore the long‐term outcomes and safety of metformin as an alternative for treating gestational diabetes.
First report of Pauesia silana Tremblay, 1969 (Hymenoptera: Aphidiidae), a natural enemy of the aphid Cinara pini L., in Algeria
Authors: Benhamacha M. , Ghezali D. , Chemala A. , Marniche F. 
Published: June 2017

A survey of aphids and their parasitoids in a garden park located in Algiers from March 2015 to March 2016 detected the presence of Cinara pini Linnaeus, 1758 for the first time in Algiers. This species had previously been reported in one other location in Algeria. This aphid was found on Pinus nigra and Pinus halepensis. Mummies of C. pini were found to be parasitized by Pauesia silana Tremblay, 1969. This paper provides the first report of P. silana in Algeria.
Probabilistic assessment of VHCF data as pertaining to concurrent populations using a Weibull regression model
Authors: Muniz‐Calvente M. , Fernández‐Canteli A. , Pyttel B. , Castillo E. 
Published: June 2017

AbstractThe Weibull regression model proposed by Castillo and Canteli to evaluate fatigue results represents a possible and adequate option to be used for the assessment and prediction of very high cycle fatigue (VHCF) lifetimes. Among others, this model provides a probabilistic definition of the S‐N field for determining failure mechanisms, ie, internal and surface ones, based on extreme value distributions of the Weibull family for minima, as well as the existence of an asymptotic fatigue limit and the capability to reduce the S‐N field to a single cumulative distribution function by considering the normalized variable V = (log N‐B) (log Δσ). In this way, both dual fracture mechanisms characterizing the VHCF data can be adequately interpreted and handled as independent distributions in such a particular and complex case of concurrent populations, known statistically as a confounded data problem. Once the model parameters of both normalized cumulative distribution functions are estimated, the probability of failure for any of both failure mechanisms at whatever stress range can be determined by applying a back normalization to the original Wöhler field. Two examples of application are presented, the first one to introduce the proposed methodology by means of an example with simulated data to show the reliability of the proposed approach to fit correctly the model parameters assumed for the simulation, and the second one, using real results from a former external experimental VHCF program. Finally, a test strategy, which optimizes the planning of the fatigue program, is suggested.
Salish Sea Chinook salmon exhibit weaker coherence in early marine survival trends than coastal populations
Authors: Ruff Casey P. , Anderson Joseph H. , Kemp Iris M. , Kendall Neala W. , Mchugh Peter A. , Velez‐Espino Antonio , Greene Correigh M. , Trudel Marc , Holt Carrie A. , Ryding Kristen E. , Rawson Kit 
Published: June 2017

AbstractIdentifying factors that influence anadromous Pacific salmon (Oncorhynchus spp.) population dynamics is complicated by their diverse life histories and large geographic range. Over the last several decades, Chinook salmon (O. tshawytscha) populations from coastal areas and the Salish Sea have exhibited substantial variability in abundance. In some cases, populations within the Salish Sea have experienced persistent declines that have not rebounded. We analyzed a time series of early marine survival from 36 hatchery Chinook salmon populations spanning ocean entry years 1980–2008 to quantify spatial and temporal coherence in survival. Overall, we observed higher inter‐population variability in survival for Salish Sea populations than non‐Salish Sea populations. Annual survival patterns of Salish Sea populations covaried over smaller spatial scales and exhibited less synchrony among proximate populations relative to non‐Salish Sea populations. These results were supported by multivariate autoregressive state space (MARSS) models which predominantly identified region‐scale differences in survival trends between northern coastal, southern coastal, Strait of Georgia, and Puget Sound population groupings. Furthermore, Dynamic Factor Analysis (DFA) of regional survival trends showed that survival of southern coastal populations was associated with the North Pacific Gyre Oscillation, a large‐scale ocean circulation pattern, whereas survival of Salish Sea populations was not. In summary, this study demonstrates that survival patterns in Chinook salmon are likely determined by a complex hierarchy of processes operating across a broad range in spatial and temporal scales, presenting challenges to the management of mixed‐stock fisheries.