bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study
Authors: Szalecki Mieczysław , Wysocka‐Mincewicz Marta , Ramotowska Anna , Mazur Artur , Lisowicz Lucyna , Beń‐Skowronek Iwona , Sieniawska Joanna , Klonowska Bożena , Charemska Dorota , Nawrotek Jolanta , Jałowiec Irena , Bossowski Artur , Jamiołkowska Milena , Pyrżak Beata , Miszkurka Grażyna , Szypowska Agnieszka 
Published: November 2017

AbstractBackgroundThe incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland.MethodsIn this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland.ResultsOverall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17‐year‐olds. In the urban population (age 0‐17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas.ConclusionsThe incidence of T1D in children living in eastern and central Poland increased 1.5‐fold over the 5‐year observation period with the highest rise in 10 to 14‐year‐olds and significantly higher rates in urban children compared with their peers living in rural areas.
Reintroduction of the endangered and endemic plant speciesCochlearia bavarica—Implications from conservation genetics
Authors: Kaulfuß Franziska , Reisch Christoph 
Published: November 2017

AbstractPopulation reintroduction is a common practice in conservation, but often fails, also due to the effects of inbreeding or outbreeding depression.Cochlearia bavaricais a strongly endangered plant species endemic to Bavaria in Germany, constantly declining since the late 1980s. Therefore, population reintroduction is intended. In this study, we analyzed genetic diversity within and genetic differentiation between all 32 remnant populations of the species in Swabia and Upper Bavaria using amplified fragment length polymorphisms. Our aim was to increase reintroduction success by providing data to avoid negative effects of inbreeding and outbreeding and to preserve the natural genetic pattern of the species. Genetic diversity within populations was low but similar to other rare and endemic species and varied strongly between populations but did not depend on population size. Our analysis revealed a strong geographic pattern of genetic variation. Genetic differentiation was strongest between Swabia and Upper Bavaria and at the population level, whereas differentiation between subpopulations was comparatively low. Isolation by distance and genetic differentiation was stronger among populations from Upper Bavaria than from Swabia. From the results of our study, we derived recommendations for a successful reintroduction of the species. We suggest using rather genetically variable than large populations as reintroduction sources. Moreover, the exchange of plant material between Swabia and Upper Bavaria should be completely avoided. Within these regions, plant material from genetically similar populations should preferably be used for reintroduction, whereas the exchange among subpopulations seems to be possible without a negative impact on genetic variation due to natural gene flow.
The value of information for woodland management: updating a state–transition model
Authors: Morris William K. , Runge Michael C. , Vesk Peter A. 
Published: November 2017

AbstractValue of information (VOI) analyses reveal the expected benefit of reducing uncertainty to a decision maker. Most ecological VOI analyses have focused on population models rarely addressing more complex community models. We performed a VOI analysis for a complex state–transition model of Box‐Ironbark Forest and Woodland management. With three management alternatives (limited harvest/firewood removal (HF), ecological thinning (ET), and no management), managing the system optimally (for 150 yr) with the original information would, on average, increase the amount of forest in a desirable state from 19% to 35% (a 16‐percentage point increase). Resolving all uncertainty would, on average, increase the final percentage to 42% (a 19‐percentage point increase). However, only resolving the uncertainty for a single parameter was worth almost two‐thirds the value of resolving all uncertainty. We found the VOI to depend on the number of management options, increasing as the management flexibility increased. Our analyses show it is more cost‐effective to monitor low‐density regrowth forest than other states and more cost‐effective to experiment with the no‐management alternative than the other management alternatives. Importantly, the most cost‐effective strategies did not include either the most desired forest states or the least understood management strategy, ET. This implies that managers cannot just rely on intuition to tell them where the most VOI will lie, as critical uncertainties in a complex system are sometimes cryptic.
Multiple species of cuckoos are superior predictors of bird species richness in Asia
Authors: Møller Anders Pape , Morelli Federico , Benedetti Yanina , Mousseau Timothy , Su Tongping , Zhou Bo , Tryjanowski Piotr , Liang Wei 
Published: November 2017

AbstractThe abundance and the presence of common cuckoos Cuculus canorus have been shown to predict species richness of birds across Europe, while there are no such analyses available for other continents where species richness of parasitic cuckoos is larger. Here, we tested whether species richness of birds increased with the number of cuckoo species in two study areas in China and one in Japan. We also tested whether species richness of birds can be predicted by the number of cuckoo individuals. Furthermore, we compared the strength of association between overall bird species richness and species richness of cuckoos, Paridae, Corvidae, and birds of prey. This is the first study demonstrating that cuckoo species richness is more strongly associated with overall bird species richness than richness of species belonging to other families, and rather than occurrence of a single cuckoo species, as already demonstrated for the common cuckoo in Europe. The number of cuckoo species was positively associated with both non‐host and host species richness. We found evidence of the number of cuckoo species being associated with species richness of birds independently of country and year, while abundance of individual cuckoos was not a statistically significant predictor. Furthermore, we showed that richness of host species is strongly positively correlated with overall bird species richness in both countries. This implies that the high species richness of cuckoos in South‐East Asia is a reliable predictor of overall bird species richness.
Calcineurin inhibitor‐induced complement system activation via ERK1/2 signalling is inhibited by SOCS‐3 in human renal tubule cells
Authors: Loeschenberger Beatrix , Niess Lea , Würzner Reinhard , Schwelberger Hubert , Eder Iris E. , Puhr Martin , Guenther Julia , Troppmair Jakob , Rudnicki Michael , Neuwirt Hannes 
Published: November 2017

AbstractOne factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C‐) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C‐system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C‐factors and downregulated SOCS‐3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/‐2 was required for these regulations. Following knock‐down and overexpression of SOCS‐3, we found that SOCS‐3 inhibits ERK1/‐2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component‐depleted conditions. In vivo, increased ERK1/‐2 phosphorylation and SOCS‐3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow‐up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS‐3 inhibits CNI‐induced ERK1/‐2 signalling, thereby blunting the negative control of C‐system activation.
Electrocatalytic Oxidation of Carbohydrates Mediated by Nitroxyl Radical‐modified Electrodes in Aqueous Solution
Authors: Ono Tetsuya , Sato Katsuhiko , Shimizu Syunki , Yoshida Kentaro , Dairaku Takenori , Suzuki Yasuhiro , Kashiwagi Yoshitomo 
Published: November 2017

AbstractThe electrocatalytic activity of a 2,2,6,6‐tetramethylpipridine‐N‐oxyl (TEMPO)‐modified electrode toward the oxidation of carbohydrates in phosphate buffer solution was investigated under neutral aqueous solution conditions at 25 °C. The modified electrode was prepared on the surface of a glassy carbon electrode by the electrochemical polymerization of a TEMPO precursor containing a pyrrole side chain. Cyclic voltammetric studies showed that the anodic peak current increased with the concentration of carbohydrates in a dose‐dependent manner.
A critical role of TRPM2 channel in Aβ42‐induced microglial activation and generation of tumor necrosis factor‐α
Authors: Alawieyah Syed Mortadza Sharifah , Sim Joan A. , Neubrand Veronika E. , Jiang Lin‐Hua 
Published: November 2017

AbstractAmyloid β (Aβ)‐induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin‐related 2 (TRPM2) channel in Aβ‐induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor‐α (TNF‐α), a key cytokine implicated in AD. Exposure to 10–300 nM Aβ42 induced concentration‐dependent microglial activation and generation of TNF‐α that were ablated by genetically deleting (TRPM2 knockout ;TRPM2‐KO) or pharmacologically inhibiting the TRPM2 channel, revealing a critical role of this channel in Aβ42‐induced microglial activation and generation of TNF‐α. Mechanistically, Aβ42 activated the TRPM2 channel via stimulating generation of reactive oxygen species (ROS) and activation of poly(ADPR) polymerase‐1 (PARP‐1). Aβ42‐induced generation of ROS and activation of PARP‐1 and TRPM2 channel were suppressed by inhibiting protein kinase C (PKC) and NADPH oxidases (NOX). Aβ42‐induced activation of PARP‐1 and TRPM2 channel was also reduced by inhibiting PYK2 and MEK/ERK. Aβ42‐induced activation of PARP‐1 was attenuated by TRPM2‐KO and moreover, the remaining PARP‐1 activity was eliminated by inhibiting PKC and NOX, but not PYK2 and MEK/ERK. Collectively, our results suggest that PKC/NOX‐mediated generation of ROS and subsequent activation of PARP‐1 play a role in Aβ42‐induced TRPM2 channel activation and TRPM2‐dependent activation of the PYK2/MEK/ERK signalling pathway acts as a positive feedback to further facilitate activation of PARP‐1 and TRPM2 channel. These findings provide novel insights into the mechanisms underlying Aβ‐induced AD‐related neuroinflammation.
Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study
Authors: Saarelainen Laura , Tolppanen Anna‐Maija , Koponen Marjaana , Tanskanen Antti , Tiihonen Jari , Hartikainen Sirpa , Taipale Heidi 
Published: November 2017

ObjectiveTo investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).MethodsThe register‐based MEDALZ cohort, including all community‐dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded.For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180‐day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.ResultsDuring the follow‐up, 5 excess deaths per 100 person‐years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2‐14.5) and 8.5 (95% CI, 7.9‐9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2‐1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine‐related drug use was not.ConclusionsBenzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first‐line option for symptomatic treatment of AD.
Central pain processing in “drug‐naïve” pain‐free patients with Parkinson's disease
Authors: Tessitore Alessandro , Russo Antonio , De Micco Rosa , Fratello Michele , Caiazzo Giuseppina , Giordano Alfonso , Cirillo Mario , Tedeschi Gioacchino , Esposito Fabrizio 
Published: November 2017

AbstractBackgroundDespite its clinical relevance, the pathophysiology of pain in Parkinson's disease (PD) is still largely unknown, and both central and peripheral mechanisms have been invoked.ObjectivesTo investigate whether central pain processing is altered in “drug‐naive” pain‐free PD (dnPD) patients.MethodsUsing event‐related functional MRI (fMRI), functional response to forearm heat stimulation (FHS) at two different intensities (41°C and 53°C) was investigated in 20 pain‐free dnPD patients, compared with 18 healthy controls (HCs). Secondary analyses were performed to evaluate associations between BOLD signal changes and PD clinical features and behavioral responses.ResultsDuring low‐innocuous FHS (41°C), no activation differences were found between dnPD patients and HCs. During high‐noxious FHS (53°C) a significantly increased activation in the left somatosensory cortex, left cerebellum, and right low pons was observed in dnPD patients compared to HCs. In the latter experimental condition, fMRI BOLD signal changes in the right low pons (p < .0001; R = −0.8) and in the cerebellum (p = .004; R = −0.7) were negatively correlated with pain intensity ratings only in dnPD patients. No statistically significant difference in experimental pain perception was detected between dnPD patients and HCs.ConclusionsOur findings suggest that a functional remodulation of pain processing pathways occurs even in the absence of clinically overt pain symptoms in dnPD patients. These mechanisms may eventually become dysfunctional over time, contributing to the emergence of pain symptoms in more advanced PD stages. The comprehension of pain‐related mechanisms may improve the clinical approach and therapeutic management of this disabling nonmotor symptom.
Intermittent compressive force induces human mandibular‐derived osteoblast differentiation via WNT/β‐catenin signaling
Authors: Sindhavajiva Pimrumpai R. , Sastravaha Panunn , Arksornnukit Mansuang , Pavasant Prasit 
Published: November 2017

AbstractMechanical force induces an efflux of ATP that regulates osteoblast differentiation. However, the effect of mechanical force‐induced ATP efflux on WNT/β‐catenin signaling remains unclarified. The aim of this study was to investigate the effect of intermittent compressive force (ICF) and ICF‐induced extracellular ATP on osteoblast differentiation via WNT/β‐catenin signaling in human mandibular‐derived osteoblast precursors (hMOBPs). The hMOBPs were subjected to ICF (1.5 g/cm2, 0.3 Hz) for 20 h. To investigate the role of ATP, Apyrase (0.5 units/mL), an enzyme that hydrolyzes ATP, was added 30 min before ICF was applied. The extracellular ATP levels were measured immediately after ICF was removed. The mRNA expression of osteogenic related genes, including WNT was evaluated via quantitative real time polymerase chain reaction. In vitro mineralization was determined by Alizarin Red S staining. The localization of β‐catenin was detected using immunofluorescence staining and lentiviral‐TOP‐dGFP reporter assay. The results demonstrated that ICF increased ATP efflux and in vitro mineralization by hMOBPs. In addition, OSX, ALP, and WNT3A mRNA expression and β‐catenin nuclear translocation increased when ICF was applied. The upregulation of these genes was reduced by Apyrase, suggesting the role of ICF‐induced ATP on osteoblast differentiation. Notably, ICF altered the mRNA expression of purinergic 2X receptors (P2XRs). A P2X1R antagonist (NF449) downregulated ICF‐induced WNT3A, OSX, and ALP mRNA expression. Moreover, when 25 μM α, β‐meATP, a P2X1R agonist, was added, WNT3A, and OSX expression increased. In conclusion, our results demonstrate that ICF‐induced ATP enhanced hMOBP differentiation. This enhancement was associated with WNT/β‐catenin signaling and P2X1R activation.
Biological evaluation and energetic analyses of novel GSK‐3βinhibitors
Authors: Zhang Denan , Liu Lei , Pang Lin , Jin Qing , Ke Kehui , Hu Ming , Yang Jingbo , Ma Weifang , Xie Hongbo , Chen Xiujie 
Published: November 2017

AbstractGlycogen synthase kinase‐3 beta (GSK‐3β) is involved in multiple signaling pathways. Consistent with its critical roles in normal cells, abnormalities in GSK‐3βactivity have been implicated in diabetes, heart disease, Parkinson disease, and Alzheimer's disease. In this study, a series of new scaffolds of small molecule inhibitors of GSK‐3βwere identified by virtual screening and bioassay. Candidates that adhere to drug‐like criteria from a virtual library of compounds were tested using computational docking studies. Twenty selected compounds were tested, which led to the discovery of two hits. Compound14(IC50 = 8.48 µM) and compound19(IC50 = 2.19 µM) were identified with high affinity. Molecular dynamics (MD) simulations, in conjunction with molecular mechanics/Poisson‐Boltzmann surface area binding free‐energy analysis, were employed to gain insight into the binding modes and energetics of GSK‐3βinhibitors. The detailed analysis of molecular dynamics results shows that Ile62, Val70, Tyr134, and Leu188 in GSK‐3βare key residues responsible to the binding of compound14and compound19. Importantly, our results also validated this combined virtual screening and biophysical technique approach to discovery kinase inhibitors, which may be applied for future inhibitor discovery work for GSK‐3β.
A new and important relationship between miRNA‐147a and PDPK1 in radiotherapy
Authors: Wang Li‐Juan , Li Na‐Na , Xu Sai‐Juan , Zhang Fan , Hao Ming‐Hua , Yang Xian‐Jun , Cai Xin‐Hua , Qiu Pei‐Yong , Ji Hong‐Long , Xu Ping 
Published: November 2017

AbstractIt was found that the expression level of miR‐147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR‐147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR‐147 (a or b) and PI3K/AKT signaling pathway. miR‐147a overexpression plasmid and PDPK1 3′UTR luciferase reporter gene plasmid were constructed. Dual luciferase reporter gene system validation experiments were carried out on miR‐147a and PDPK1 relationship. The verification experiments were also carried out. Bioinformatics analysis showed that there is a miR‐147a binding site in the non‐coding region (3′UTR) of PDPK1. In the experimental groups transfected with wild type PDPK1 gene of 3′UTR plasmid, the luciferase activity decreased (or increased) significantly in miR‐147a (or inhibitor) group compared with miR‐NC (or anti‐miR‐NC); There was no significant difference between the miR‐147a group (or inhibitor) and the miR‐NC group (or anti‐miR‐NC) in the transfection of PDPK1‐3′UTR‐Mut gene vector. PDPK1 was a target gene for direct regulation of miR‐147a downstream. Verifying test results showed that the expression of PDPK1 mRNA and protein was reduced after overexpression of miR‐147a, which was up‐regulated after silencing miR‐147a in TC, and V79 cells. These results suggest that miR‐147a could be involved in the regulation of PDPK1 transcription by binding to the target site in PDPK1 mRNA 3′UTR, and then regulated AKT.
Retracted: Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k‐Akt signaling pathway
Authors: Ao Ran , Guan Lin , Wang Ying , Wang Jia‐Ni 
Published: November 2017

AbstractThis study explores the effect of COL1A2, COL6A3, and THBS2 gene silencing on proliferation, migration, invasion, and apoptosis of gastric cancer cells through the PI3K‐Akt signaling pathway. The gastric cancer microarray expression data (GSE19826, GSE79973, and GSE65801) was analyzed. Gastric cancer tissues and corresponding adjacent normal tissues were extracted from patients. Positive expression rate of PI3K, Akt, and p‐Akt was measured with immunohistochemistry. Two cell lines, BGC‐823 and SGC‐7901, were transfected and cells were grouped into blank, negative control, COL1A2‐shRNA, COL6A3‐shRNA, and THBS2‐shRNA groups. Expressions of COL1A2, COL6A3, and THBS2 in gastric cancer cells transfected with corresponding silencing sequences were evaluated by RT‐qPCR and Western blot. MTT assay, Transwell, and cell scratch tests were conducted to evaluate cell proliferation, invasion, and migration capacity, respectively. Flow cytometry was used to evaluate cell cycle distribution and apoptosis. The positive expression of PI3K, Akt, and p‐Akt was higher in gastric cancer tissues compared with adjacent normal tissues, and the mRNA expression of COL1A2, COL6A3, and THBS2 was increased in gastric cancer tissues. Akt, p‐Akt, and PI3K expression drastically decreased in cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences. Cells transfected with COL1A2, COL6A3, and THBS2 silencing sequences exhibited promoted apoptosis but inhibited proliferation, migration, and invasion. This study demonstrates that COL1A2, COL6A3, and THBS2 gene silencing inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3K‐Akt signaling pathway.