bluuebunny/crossref_metadata_2025 huggingface dataset:
A combinatorial strategy of alternative promoter use during differentiation of a heterocystous cyanobacterium
Authors: Muro‐Pastor Alicia M. , Brenes‐Álvarez Manuel , Vioque Agustín
Published: June 2017

Heterocystous cyanobacteria such as Nostoc sp. are filamentous photosynthetic organisms that, in response to nitrogen deficiency, undergo a differentiation process transforming certain, semi‐regularly spaced cells into heterocysts, devoted to nitrogen fixation. During transition to a nitrogen‐fixing regime, growth of most vegetative cells in the filament is temporarily arrested due to nutritional deprivation, but developing heterocysts require intense transcriptional activity. Therefore, the coexistence of arrested vegetative cells and actively developing prospective heterocysts relies on the simultaneous operation of somewhat opposite transcriptional programs. We have identified genes with multiple nitrogen‐responsive transcriptional starts appearing in seemingly paradoxical combinations. For instance, sigA, encoding the RNA polymerase housekeeping sigma factor, is transcribed from one major nitrogen stress‐repressed promoter and from a second, nitrogen stress‐induced promoter. Here, we show that both promoters are expressed with complementary temporal dynamics. Using a gfp reporter we also show that transcription from the inducible promoter takes place exclusively in differentiating heterocysts and is already detected before any morphological or fluorescence signature of differentiation is observed. Tandem promoters with opposite dynamics could operate a compensatory mechanism in which repression of transcription from the major promoter operative in vegetative cells is offset by transcription from a new promoter only in developing heterocyst.
Coercive Leadership
Authors: Landa Dimitri , Tyson Scott A.
Published: June 2017

We develop a model of leadership in which an informed leader has some degree of coercive influence over her followers (agents). Agents benefit from coordination but face two distinct challenges: dispersed information and heterogeneous preferences. The leader's coercive power facilitates coordination by weakening the effect presented by both of these challenges through “binding” agents to a strategically chosen policy. The leader's policy choice becomes more informative to the agents about the leader's privately held information as her coercive capacity increases. By adjusting her policy choice in response to available private and public information, the coercive leader achieves her preferred average of agents' actions, and in so doing, neutralizes the possibly deleterious coordinating influence of public information. We develop implications of our analysis for understanding autocratic leadership in different political and organizational contexts.
Sentinel node biopsy for early breast cancer in Queensland, Australia, during 2008–2012
Authors: Dasgupta Paramita , Youl Philippa H. , Pyke Christopher , Aitken Joanne F. , Baade Peter D.
Published: June 2017

Background

Sentinel node biopsy (SNB) is now the standard of care for women with early‐stage breast cancer. Despite lower morbidity than axillary lymph node dissection, widespread variation in SNB rates by non‐clinical factors persists. We explored the factors associated with SNB usage and changes in those associations over time for recently diagnosed women.

Methods

We report here on a linked population‐based cancer registry and hospital inpatient admission data set for 5577 women aged at least 20 years diagnosed with a first primary invasive early‐stage node‐negative breast cancer from July 2008 to 2012 in Queensland, Australia, who underwent breast cancer‐related surgery within 2 years of diagnosis. Multivariate logistic regression was used to model predictors of SNB separately for 5172 women with ≤30 mm tumours and 405 with 31 to ≤50 mm tumours.

Results

Overall, 3972 (77%) women with ≤30 mm tumours and 221 (55%) of those with larger tumours underwent SNB. Usage increased over time for both cohorts but was consistently lower among those with larger tumours. A more recent diagnosis, having breast‐conserving surgery, living in more accessible areas and attending a private or high‐volume hospital independently increased the odds of SNB for both cohorts. There was no evidence that the geographical disparity had reduced over the study period for either cohort.

Conclusion

Geographical disparities to accessing SNB persist. Efforts to promote multidisciplinary care and facilitate education in healthcare changes through innovative solutions using emerging technologies as well as targeted research to identify the barriers to equitable access remain critical.
Inadequate adherence to Swedish guidelines for uncomplicated lower urinary tract infections among adults in general practice
Authors: Lindbäck Heidi , Lindbäck Johan , Melhus Åsa
Published: June 2017

In a primary care study of urinary tract infections (UTIs) performed 2008 in Uppsala County, Sweden, 43% of the patients were culture negative. In order to investigate the background to the observed overdiagnosis of UTI, study invitations were sent to the previously included patients. A total of 256 patients (88% women) approved to participate. Patient charts and recorded laboratory data were reviewed. Two or more of the cardinal symptoms were reported in 53% of the women and in 19% of the men. A dipstick test was performed in 93% of the consultations. The highest positive predicted values in women had a positive nitrite test (95%, 95% CI 87; 99) and dysuria in combination with urgency (81%, 95% CI 72; 88). Seventy‐one percent of the women who fulfilled the symptom criteria received an antibiotic prescription directly, 87% of these had a positive culture. The drug of choice was pivmecillinam for women (51%) and quinolones (50%) for men. The treatment duration was too long for the women; 68% were treated for ≥7 days. In conclusion, the adherence to national guidelines/recommendations was inadequate. To reduce the selection of multiresistant bacteria, an improvement of the use of diagnostic criteria/tools and antibiotic drugs in primary care is necessary.
A DNA hypermethylation profile reveals new potential biomarkers for the evaluation of prognosis in urothelial bladder cancer
Authors: López Jose I. , Angulo Javier C. , Martín Ana , Sánchez‐Chapado Manuel , González‐Corpas Ana , Colás Begoña , Ropero Santiago
Published: June 2017

DNA hypermethylation has emerged as a molecular biomarker for the evaluation of cancer diagnosis and prognosis. We define a methylation signature of bladder cancer and evaluate whether this profile assesses prognosis of patients. Genome‐wide methylation analysis was performed on 70 tumor and 10 normal bladder samples. Hypermethylation status of 1505 CpGs present in the promoter region of 807 genes was studied. Thirty‐three genes were significantly hypermethylated in ≥10% of the tumors. Three clusters of patients were characterized by their DNA methylation profile, one at higher risk of dead of disease (p = 0.0012). Association between cluster distribution and stage (p = 0.02) or grade (p = 0.02) was demonstrated. Hypermethylation of JAK3 and absence of hypermethylation of EYA4, GAT6, and SOX1 were associated with low‐grade non‐invasive disease. On the other hand, in high‐grade invasive disease hypermethylation of CSPG2, HOXA11, HOXA9, HS3ST2, SOX1, and TWIST1 was associated with muscle invasiveness. A panel of hypermethylated genes including APC, CSPG2, EPHA5, EYA4, HOXA9, IPF1, ISL1, JAK3, PITX2, SOX1, and TWIST1 predicted cancer‐specific survival and SOX1 (HR = 3.46), PITX2 (HR = 4.17), CSPG2 (HR = 5.35), and JAK3 hypermethylation (HR = 0.19) did so independently. Silencing of genes by hypermethylation is a common event in bladder cancer and could be used to develop diagnostic and prognostic markers. Combined hypermethylation of SOX1, PITX2, or CSPG2 signals patients at higher risk of death from bladder cancer.
Effects of transforming growth factor‐β1 treatment on muscle regeneration and adipogenesis in glycerol‐injured muscle
Authors: Mahdy Mohamed A. A. , Warita Katsuhiko , Hosaka Yoshinao Z.
Published: June 2017

Transforming growth factor (TGF)‐β1 is associated with fibrosis in many organs. Recent studies demonstrated that delivery of TGF‐β1 into chemically injured muscle enhances fibrosis. In this study, we investigated the effects of exogenous TGF‐β1 on muscle regeneration and adipogenesis in glycerol‐injured muscle of normal mice. Tibialis anterior (TA) muscles were injured by glycerol injection. TGF‐β1 was either co‐injected with glycerol, as an ‘early treatment’ group, or injected at day 4 after glycerol, as a ‘late treatment’ group and the TA muscles were collected at day 7 after initial injury. Myotube density was significantly lower in the early treatment group than in the glycerol‐injured group (without TGF‐β1 treatment). Moreover, the Oil red O‐positive area was significantly smaller in the early treatment group than in the late treatment group and glycerol‐injured group. Furthermore, TGF‐β1 treatment increased endomysial fibrosis and induced immunostaining of α‐smooth muscle actin. The greater inhibitory effects of early TGF‐β1 treatment than that of late TGF‐β1 treatment during regeneration in glycerol‐injured muscle suggest a more potent effect of TGF‐β1 on the initial stage of muscle regeneration and adipogenesis. Combination of TGF‐β1 with glycerol might be an alternative to enhance muscle fibrosis for future studies.
The effects of l‐DOPA and sulpiride on growth hormone secretion at different injection times in Holstein steers
Authors: Kasuya Etsuko , Sutoh Madoka , Yayou Ken‐ichi
Published: June 2017

The effects of l‐DOPA, a precursor of dopamine (DA), and sulpiride, a D2‐type DA receptor blocker, on growth hormone (GH) and prolactin (PRL) secretion were investigated in steers. Eight Holstein steers (212.8 ± 7.8 kg body weight) were used. Lighting conditions were 12:12 L:D (lights on: 06.00–18.00 hours). Blood samplings were performed during the daytime (11.00–15.00 hours) and nighttime (23.00–03.00 hours). Intravenous injections of drugs or saline were performed at 12.00 hour for the daytime and 00.00 hour for the nighttime, respectively. Plasma GH and PRL concentrations were determined by radioimmunoassay. l‐DOPA did not alter the GH secretion when it was injected at 12.00 hour (spontaneous GH level at its peak). On the other hand, l‐DOPA increased GH secretion at 00.00 hour (GH level at its trough). Injection of sulpiride suppressed GH secretion at 12.00 hour but did not affect GH levels at 00.00 hour. l‐DOPA inhibited and sulpiride stimulated PRL release during both periods. These results suggest that dopaminergic neurons have stimulatory action on GH secretion and inhibitory action on PRL secretion in cattle. In addition, injection time should be considered to evaluate the exact effects on GH secretion due to its ultradian rhythm of GH secretion in cattle.
4β‐Hydroxycholesterol level significantly correlates with steady‐state serum concentration of the CYP3A4 substrate quetiapine in psychiatric patients
Authors: Gjestad Caroline , Haslemo Tore , Andreassen Ole A. , Molden Espen
Published: June 2017

Aim

4β‐Hydroxycholesterol (4βOHC) is sensitive towards induction or inhibition of CYP3A4, but its potential usefulness as a dosing biomarker remains to be demonstrated. The aim of this study was to investigate the correlation between 4βOHC levels and steady‐state concentrations (Css) of quetiapine, a CYP3A4 substrate with high presystemic metabolism, in psychiatric patients.

Methods

Serum samples from 151 patients treated with quetiapine as immediate release (IR; n = 98) or slow release (XR; n = 53) tablets were included for analysis of 4βOHC. In all patients, Css of quetiapine had been measured at trough level, i.e. 10–14 and 17–25 h post‐dosing for IR and XR tablets, respectively. Correlations between 4βOHC levels and dose‐adjusted Css (C/D ratios) of quetiapine were tested by univariate (Spearman's) and multivariate (multiple linear regression) analyses. Gender, age (≥60 vs. <60 years) and tablet formulation were included as potential covariates in the multivariate analysis.

Results

Correlations between 4βOHC levels and quetiapine C/D ratios were highly significant both for IR‐ and XR‐treated patients (P < 0.0001). Estimated Spearman r values were −0.47 (95% confidence interval −0.62, −0.30) and −0.56 (−0.72, −0.33), respectively. The relationship between 4βOHC level and quetiapine C/D ratio was also significant in the multiple linear regression analysis (P < 0.001), including gender (P = 0.023) and age (P = 0.003) as significant covariates.

Conclusions

The present study shows that 4βOHC level is significantly correlated with steady‐state concentration of quetiapine. This supports the potential usefulness of 4βOHC as a phenotype biomarker for individualized dosing of quetiapine and other drugs where systemic exposure is mainly determined by CYP3A4 metabolism.
Understanding neurodevelopmental disorders using human pluripotent stem cell‐derived neurons
Authors: Tamburini Claudia , Li Meng
Published: June 2017

Research into psychiatric disorders has long been hindered by the lack of appropriate models. Induced pluripotent stem cells (iPSCs) offer an unlimited source of patient‐specific cells, which in principle can be differentiated into all disease‐relevant somatic cell types to create in vitro models of the disorder of interest. Here, neuronal differentiation protocols available for this purpose and the current progress on iPSCs‐based models of schizophrenia, autism spectrum disorders and bipolar disorder were reviewed. We also discuss the impact of the recently developed CRISPR/Cas9 genome editing tool in the disease modeling field. Genetically engineered mutation of disease risk alleles in well characterized reference “control” hPSCs or correction of disease risk variants in patient iPSCs has been used as a powerful means to establish causality of the identified cellular pathology. Together, iPSC reprogramming and CRISPR/CAS9 genome editing technology have already significantly contributed to our understanding of the developmental origin of some major psychiatric disorders. The challenge ahead is the identification of shared mechanisms in their etiology, which will ultimately be relevant to the development of new treatments.
Modeling the C9ORF72 repeat expansion mutation using human induced pluripotent stem cells
Authors: Selvaraj Bhuvaneish T. , Livesey Matthew R. , Chandran Siddharthan
Published: June 2017

C9ORF72 repeat expansion is the most frequent causal genetic mutation giving rise to amyotrophic lateral sclerosis (ALS) and fronto‐temporal dementia (FTD). The relatively recent discovery of the C9ORF72 repeat expansion in 2011 and the complexity of the mutation have meant that animal models that successfully recapitulate human C9ORF72 repeat expansion‐mediated disease are only now emerging. Concurrent advances in the use of patient‐derived induced pluripotent stem cells (iPSCs) to model aspects of neurological disease offers an additional approach for the study of C9ORF72 mutation. This review focuses on the opportunities of human C9ORF72 iPSC platforms to model pathological aspects of disease and how findings compare with other existing models of disease and post mortem data.
Modeling Parkinson's disease with induced pluripotent stem cells harboring α‐synuclein mutations
Authors: Singh Dolt Karamjit , Hammachi Fella , Kunath Tilo
Published: June 2017

Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non‐motor symptoms that are typical for sporadic PD. With the advent of reprogramming technology it is now possible to capture these mutations in induced pluripotent stem cells (iPSCs) to establish models of PD in a dish. There are multiple neuronal subtypes affected in PD including the midbrain dopaminergic (mDA) neurons of the substantia nigra. Robust neuronal differentiation into mDA or other relevant neural cell types are critical to accurately model the disease and ensure the findings are relevant to understanding the disease process. Another challenge for establishing accurate models of PD is being met by the generation of isogenic control iPSC lines with precise correction of mutations using advanced gene editing technology. The contributions of ageing and environmental factors present further challenges to this field, but significant progress is being made in these areas to establish highly relevant and robust models of PD. These human neuronal models, used in conjunction with other model systems, will vastly improve our understanding of the early stages of the PD, which will be key to identifying disease‐modifying and preventative treatments.
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 Purpose

Genomic 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 Approach

Mice 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 Results

Immunochemical 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 Implications

These 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 Articles

This 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 Articles

This 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 Purpose

The 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 Approach

A 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 Results

The 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 Implications

The 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

For 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

Several 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

Objective

To 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.

Methods

This 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.

Results

A 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).

Conclusion

Viral 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

Background

Reintubation is associated with increased hospital mortality. It is necessary to identify risk factors associated with reintubation.

Methods

A 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.

Results

We 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).

Conclusions

Multiple 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.
The iterative process in the development of a parent‐reported questionnaire for children with unilateral paresis
Authors: Klingels Katrijn
Published: June 2017

This commentary is on the original article by Geerdink et al. on pages 919–925 of this issue.
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

Aim

To examine patterns of use of different glycaemic control agents for treating gestational diabetes mellitus.

Methods

This 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.

Results

Our 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%).

Conclusions

Our 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

The 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

Identifying 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.
Dispersal in dendritic networks: Ecological consequences on the spatial distribution of population densities
Authors: Altermatt Florian , Fronhofer Emanuel A.
Published: June 2017

Understanding the consequences of spatial structure on ecological dynamics is a central theme in ecology. Recently, research has recognised the relevance of river and river‐analogue network structures, because these systems are not only highly diverse but also rapidly changing due to habitat modifications or species invasions.

Much of the previous work on ecological and evolutionary dynamics in metapopulations and metacommunities in dendritic river networks has been either using comparative approaches or was purely theoretical. However, the use of microcosm experiments provides the unique opportunity to study large‐scale questions in a causal and experimental framework.

We conducted replicated microcosm experiments, in which we manipulated the spatially explicit network configuration of a landscape and addressed how linear versus dendritic connectivity affects population dynamics, specifically the spatial distribution of population densities, and movement behaviour of the protist model organismTetrahymena pyriformis. We tracked population densities and individual‐level movement behaviour of thousands of individuals over time.

At the end of the experiment, we found more variable population densities between patches in dendritic networks compared to linear networks, as predicted by theory. Specifically, in dendritic networks, population densities were higher at nodes that connected to headwaters compared to the headwaters themselves and to more central nodes in the network. These differences follow theoretical predictions and emerged from the different network topologies per se. These differences in population densities emerged despite weakly density‐dependent movement.

We show that differences in network structure alone can cause characteristic spatial variation in population densities. While such differences have been postulated by theoretical work and are the underlying precondition for differential dispersal evolution in heterogeneous networks, our results may be the first experimental demonstration thereof. Furthermore, these population‐level dynamics may affect extinction risks and can upscale to previously shown metacommunity level diversity dynamics. Given that many species in natural river systems exhibit strong spatiotemporal patterns in population densities, our work suggests that abundance patterns should not only be addressed from a local environmental perspective, but may be the outcome of processes that are inherently driven by the respective habitat network structure.
Increased Arctic sea ice drift alters adult female polar bear movements and energetics
Authors: Durner George M. , Douglas David C. , Albeke Shannon E. , Whiteman John P. , Amstrup Steven C. , Richardson Evan , Wilson Ryan R. , Ben‐David Merav
Published: June 2017

Recent reductions in thickness and extent have increased drift rates of Arctic sea ice. Increased ice drift could significantly affect the movements and the energy balance of polar bears (Ursus maritimus) which forage, nearly exclusively, on this substrate. We used radio‐tracking and ice drift data to quantify the influence of increased drift on bear movements, and we modeled the consequences for energy demands of adult females in the Beaufort and Chukchi seas during two periods with different sea ice characteristics. Westward and northward drift of the sea ice used by polar bears in both regions increased between 1987–1998 and 1999–2013. To remain within their home ranges, polar bears responded to the higher westward ice drift with greater eastward movements, while their movements north in the spring and south in fall were frequently aided by ice motion. To compensate for more rapid westward ice drift in recent years, polar bears covered greater daily distances either by increasing their time spent active (7.6%–9.6%) or by increasing their travel speed (8.5%–8.9%). This increased their calculated annual energy expenditure by 1.8%–3.6% (depending on region and reproductive status), a cost that could be met by capturing an additional 1–3 seals/year. Polar bears selected similar habitats in both periods, indicating that faster drift did not alter habitat preferences. Compounding reduced foraging opportunities that result from habitat loss; changes in ice drift, and associated activity increases, likely exacerbate the physiological stress experienced by polar bears in a warming Arctic.
Widespread production of nonmicrobial greenhouse gases in soils
Authors: Wang Bin , Lerdau Manuel , He Yongli
Published: June 2017

Carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) are the three most important greenhouse gases (GHGs), and all show large uncertainties in their atmospheric budgets. Soils of natural and managed ecosystems play an extremely important role in modulating their atmospheric abundance. Mechanisms underlying the exchange of these GHGs at the soil–atmosphere interface are often assumed to be exclusively microbe‐mediated (M‐GHGs). We argue that it is a widespread phenomenon for soil systems to produce GHGs through nonmicrobial pathways (NM‐GHGs) based on a review of the available evidence accumulated over the past half century. We find that five categories of mechanistic process, including photodegradation, thermal degradation, reactive oxidative species (ROS) oxidation, extracellular oxidative metabolism (EXOMET), and inorganic chemical reactions, can be identified as accounting for their production. These pathways are intricately coupled among themselves and with M‐GHGs production and are subject to strong influences from regional and global change agents including, among others, climate warming, solar radiation, and alterations of atmospheric components. Preliminary estimates have suggested that NM‐GHGs could play key roles in contributing to budgets of GHGs in the arid regions, whereas their global importance would be enhanced with accelerated global environmental changes. Therefore, more research should be undertaken, with a differentiation between NM‐GHGs and M‐GHGs, to further elucidate the underlying mechanisms, to investigate the impacts of various global change agents, and to quantify their contributions to regional and global GHGs budgets. These efforts will contribute to a more complete understanding of global carbon and nitrogen cycling and a reduction in the uncertainty of carbon‐climate feedbacks in the Earth system.
Tree‐ring analysis and modeling approaches yield contrary response of circumboreal forest productivity to climate change
Authors: Tei Shunsuke , Sugimoto Atsuko , Yonenobu Hitoshi , Matsuura Yojiro , Osawa Akira , Sato Hisashi , Fujinuma Junichi , Maximov Trofim
Published: June 2017

Circumboreal forest ecosystems are exposed to a larger magnitude of warming in comparison with the global average, as a result of warming‐induced environmental changes. However, it is not clear how tree growth in these ecosystems responds to these changes. In this study, we investigated the sensitivity of forest productivity to climate change using ring width indices (RWI) from a tree‐ring width dataset accessed from the International Tree‐Ring Data Bank and gridded climate datasets from the Climate Research Unit. A negative relationship of RWI with summer temperature and recent reductions in RWI were typically observed in continental dry regions, such as inner Alaska and Canada, southern Europe, and the southern part of eastern Siberia. We then developed a multiple regression model with regional meteorological parameters to predict RWI, and then applied to these models to predict how tree growth will respond to twenty‐first‐century climate change (RCP8.5 scenario). The projections showed a spatial variation and future continuous reduction in tree growth in those continental dry regions. The spatial variation, however, could not be reproduced by a dynamic global vegetation model (DGVM). The DGVM projected a generally positive trend in future tree growth all over the circumboreal region. These results indicate that DGVMs may overestimate future wood net primary productivity (NPP) in continental dry regions such as these; this seems to be common feature of current DGVMs. DGVMs should be able to express the negative effect of warming on tree growth, so that they simulate the observed recent reduction in tree growth in continental dry regions.