bluuebunny/crossref_metadata_2025_split huggingface dataset:
A2A‐D2 receptor–receptor interaction modulates gliotransmitter release from striatal astrocyte processes
Authors: Cervetto Chiara , Venturini Arianna , Passalacqua Mario , Guidolin Diego , Genedani Susanna , Fuxe Kjell , Borroto‐Esquela Dasiel O. , Cortelli Pietro , Woods Amina , Maura Guido , Marcoli Manuela , Agnati Luigi F. 
Published: November 2016

AbstractEvidence for striatal A2A‐D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes’ participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4‐aminopyridine‐evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co‐expressed on the same astrocyte processes. Evidence for A2A‐D2 receptor–receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A‐D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor‐mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A‐D2 receptors that via allosteric receptor–receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders.
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The synaptic vesicle protein SV31 assembles into a dimer and transports Zn2+
Authors: Waberer Lisa , Henrich Erik , Peetz Oliver , Morgner Nina , Dötsch Volker , Bernhard Frank , Volknandt Walter 
Published: November 2016

AbstractThe integral synaptic vesicle protein SV31 has been shown to bind divalent cations. Here, we demonstrate that SV31 protein synthesized within a cell‐free system binds Zn2+ and to a lower extent Ni2+ and Cu2+ ions. Expression with Zn2+ stabilized the protein and increased solubility. SV31 was preferentially monomeric in detergent and revealed specific binding of Zn2+. When co‐translationally inserted into defined nanodisc bilayers, SV31 assembled into dimeric complexes, resulting in increased binding of Zn2+. Putative Zn2+‐binding motifs within SV31 comprise aspartic acid and histidine residues. Site‐directed mutagenesis of two conserved aspartic acid residues leads to a potent decrease in Zn2+ binding but did not affect dimerization. Chemical modification of histidine residues abolished some of the Zn2+‐binding capacity. We demonstrate proton‐dependent transport of Zn2+ as by accumulation of fluorescent FluoZin‐1 inside of SV31‐containing proteoliposomes. Transport activity has a Km value of 44.3 μM and required external Zn2+ and internal acidic pH. Our results demonstrate that the synaptic vesicle‐integral protein SV31 functions as a proton‐dependent Zn2+ transporter. SV31 may attribute specific and yet undiscovered functions to subsets of synapses.
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Multiple pathways for elevating extracellular adenosine in the rat hippocampal CA1 region characterized by adenosine sensor cells
Authors: Yamashiro Kunihiko , Fujii Yuki , Maekawa Shohei , Morita Mitsuhiro 
Published: November 2016

AbstractExtracellular adenosine in the brain, which modulates various physiological and pathological processes, fluctuates in a complicated manner that reflects the circadian cycle, neuronal activity, metabolism, and disease states. The dynamics of extracellular adenosine in the brain are not fully understood, largely because of the lack of simple and reliable methods of measuring time‐dependent changes in tissue adenosine distribution. This study describes the development of a biosensor, designated an adenosine sensor cell, expressing adenosine A1 receptor, and a genetically modified G protein. This biosensor was used to characterize extracellular adenosine elevation in brain tissue by measuring intracellular calcium elevation in response to adenosine. Placement of adenosine sensor cells below hippocampal slices successfully detected adenosine releases from these slices in response to neuronal activity and astrocyte swelling by conventional calcium imaging. Pharmacological analyses indicated that high‐frequency electrical stimulation‐induced post‐synaptic adenosine release in a manner dependent on L‐type calcium channels and calcium‐induced calcium release. Adenosine release following treatments that cause astrocyte swelling is independent of calcium channels, but dependent on aquaporin 4, an astrocyte‐specific water channel subtype. The ability of ectonucleotidase inhibitors to inhibit adenosine release following astrocyte swelling, but not electrical stimulation, suggests that the former reflects astrocytic ATP release and subsequent enzymatic breakdown, whereas the latter reflects direct adenosine release from neurons. These results suggest that distinct mechanisms are responsible for extracellular adenosine elevations by neurons and astrocytes, allowing exquisite regulation of extracellular adenosine in the brain.
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Evaluation of the effects of acne vulgaris on quality of life in Turkey by using TAQLI
Authors: Gokalp Hilal , Bulur Isil , Kaya Erdoğan Hilal , Karapınar Tekden , Bilgin Muzaffer 
Published: November 2016

SummaryBackgroundAcne vulgaris (AV) is a chronic, inflammatory skin disease that may cause various psychiatric and/or psychological problems.ObjectiveIn this study, we aimed to determine the effect of AV on the quality of life in the Turkish population using the Turkish Acne Quality of Life Index (TAQLI).MethodsA total of 960 patients with AV who attended the dermatology department were included in the study. Acne severity was determined using the global acne classification system. TAQLI was used to evaluate the effect of acne on quality of life.ResultsThe 960 patients consisted of 673 (70.1%) females and 287 (29.9%) males. There were 536 (55.8%) patients under the age of 20, 386 (40.2%) aged 20–30, and 38 (4.0%) over 30. Acne duration varied between 1 and 20 years, and the mean duration was 2.95 ± 2.53 years. The mean TAQLI value of all patients was 20.8 ± 9.5. The mean TAQLI value was statistically significantly higher in female patients, in patients with an acne duration of more than 2 years, and in those with very severe acne. However, no statistically significant difference was found between the age groups.ConclusionWe observed that the quality of life in patients with AV was affected, and this effect was more significant in female patients, patients with severe acne and longer acne duration. We believe that the psychiatric/psychological effects should be followed up closely in this group of patients.
Eosinophilic esophagitis: unclear roles of IgE and eosinophils
Authors: Blanchard C. , Simon D. , Schoepfer A. , Straumann A. , Simon H.‐U. 
Published: November 2016

AbstractEosinophilic esophagitis (EoE) is a chronic inflammatory disease of the oesophagus. Recognized as a distinct entity only two decades ago, the emergence of the disease along with the availability of new technologies has rapidly opened new research avenues and outlined the main features of the pathogenesis of EoE. Yet, each advance in our understanding of the disease has raised new questions about the previous consensus. Currently, new subsets of the disease challenge our diagnostic criteria. For instance, it was believed that EoE did not respond to proton pump inhibitor (PPI) therapy; however, it has now been shown that a substantial proportion of EoE patients indeed respond to PPIs. In addition, a new subset of patients not even presenting eosinophil infiltrates in the oesophagus has also been described. Moreover, approaches for better understanding the heritability of the disease bring into question the dogma of predominant genetic involvement. Furthermore, the specificity and sensitivity of allergy testing for targeted food avoidance is highly controversial, and the production of specific antibodies in EoE now includes IgG4 in addition to IgE. In conclusion, EoE is perceived as ‘a moving target’ and the aim of this review was to summarize the current understanding of EoE pathogenesis.
A risk factor‐based model for upper aerodigestive tract cancers in India: predicting and validating the receiver operating characteristic curve
Authors: Gupta Bhawna , Kumar Narinder , Johnson Newell W. 
Published: November 2016

BackgroundA study was conducted to develop and validate a screening model using risk scores to identify individuals at high risk for developing upper aerodigestive tract (UADT) cancers in an Indian population.MethodsA hospital‐based case–control study (n = 480) was conducted in Pune, India. We assessed risk factors for UADT cancers by administering a questionnaire through face‐to‐face interviews. We developed a risk factor model based on the statistically significant risk factors in multiple logistic regression. A total, single risk score was calculated per individual based on the adjusted odds ratio for each of their risk factors. Standard receiver operator characteristic curve was plotted for the total score and the presence of UADT cancers. The stratification ability of the model was determined using the c‐statistic. The optimal criterion value was determined at the point on curve at which the Youden's index was maximal. Confidence intervals were calculated by bootstrapping.ResultsTotal risk score for each individual ranged from 0 to 26. Area under the receiver operating characteristic curve (95.8; P < 0.001) suggests strong predictive ability. A risk score criterion value of ≤10 produced optimal sensitivity (93.5%), specificity (71.1%), false‐positive rate (28.8%), false‐negative rate (6.4%), positive predictive value (74.8%), and negative predictive value (96.6%).ConclusionThis risk factor‐based model has the potential of satisfactorily screening and detection of UADT cancers at its early stage in a high‐risk population like India. The identified at‐risk individuals can then be targeted for clinical examination and for focused preventive/treatment measures at the hospital.
Tadalafil Improves Symptoms, Erectile Function and Quality of Life in Patients with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (KYU‐PRO Study)
Authors: TAKAHASHI Ryosuke , MIYAZATO Minoru , NISHII Hisae , SUMINO Yasuhiro , TAKAYAMA Kazuo , ONZUKA Masako , OSHIRO Takuma , SAITO Seiichi , FUJIMOTO Naohiro , MIMATA Hiromitsu , ETO Masatoshi 
Published: November 2016

ObjectivesEffect of tadalafil on lower urinary tract symptoms (LUTS), erectile function and quality of life (QoL) were prospectively evaluated in patients with benign prostatic hyperplasia (BPH) at multicenter.MethodsEligible men were ≥40 years who had no treatment with alpha‐blocker for BPH, with total International Prostate Symptom Score (IPSS) ≥8, IPSS‐QOL ≥2 and prostate volume ≥20 mL. Data were collected on age, body mass index (BMI), and prostate specific antigen (PSA). Patients were asked to complete a self‐reported questionnaire regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), and Medical Outcome Study 8‐Item Short‐Form Health Survey (SF‐8). These measures were assessed at baseline, 4‐, 8‐, 12‐week of tadalafil treatment. In addition, uroflowmetry was also performed at baseline, and 12‐week end point visit.ResultsThirty five patients with mean age 67.3 years, mean BMI 23.6 kg/m2, mean prostate volume 36 mL, and mean PSA 3.4 ng/mL were enrolled. Treatment with tadalafil significantly improved IPSS total score, IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS‐QoL score after 4 weeks and these improvements were maintained for 12‐week treatment period. IIEF5 score and general health in SF‐8 are significantly improved with the treatment of tadalafil. However, maximum flow rate and postvoiding residual volume were not significantly changed. There were not any serious adverse events.ConclusionsThese results indicate that tadalafil 5 mg once daily would be effective and well tolerated treatment in Japanese men with BPH‐LUTS.
Genetic and developmental basis for fin shape variation in African cichlid fishes
Authors: Navon Dina , Olearczyk Nathan , Albertson R. Craig 
Published: November 2016

AbstractAdaptive radiations are often characterized by the rapid evolution of traits associated with divergent feeding modes. For example, the evolutionary history of African cichlids is marked by repeated and coordinated shifts in skull, trophic, fin and body shape. Here, we seek to explore the molecular basis for fin shape variation in Lake Malawi cichlids. We first described variation within an F2 mapping population derived by crossing two cichlid species with divergent morphologies including fin shape. We then used this population to genetically map loci that influence variation in this trait. We found that the genotype–phenotype map for fin shape is largely distinct from other morphological characters including body and craniofacial shape. These data suggest that key aspects of fin, body and jaw shape are genetically modular and that the coordinated evolution of these traits in cichlids is more likely due to common selective pressures than to pleiotropy or linkage. We next combined genetic mapping data with population‐level genome scans to identify wnt7aa and col1a1 as candidate genes underlying variation in the number of pectoral fin ray elements. Gene expression patterns across species with different fin morphologies and small molecule manipulation of the Wnt pathway during fin development further support the hypothesis that variation at these loci underlies divergence in fin shape between cichlid species. In all, our data provide additional insights into the genetic and molecular mechanisms associated with morphological divergence in this important adaptive radiation.
Wealth Distribution, Elasticity of Substitution and Piketty: An ‘Anti‐Dual’ Pasinetti Economy
Authors: Zamparelli Luca 
Published: November 2016

ABSTRACTThis paper studies the dynamics of wealth distribution between workers and capitalists in a neoclassical growth model with differential saving rates. It shows that if capitalists are thriftier than workers and the factors elasticity of substitution is high enough to ensure endogenous growth, capitalists’ share of total wealth asymptotically tends to one. It is also proved that a tax on capital income shifts the long run distribution of wealth in workers’ favor, and that the capitalists’ share of total wealth is a decreasing function of the tax rate. The results of the paper are compared to Piketty's ‘fundamental laws’ of capitalism.
Insidious incrementalism: The silent failure of the microcirculation with increasing peripheral vascular disease risk
Authors: Lemaster Kent , Jackson Dwayne , Goldman Daniel , Frisbee Jefferson C. 
Published: November 2016

AbstractThis review summarizes material presented in “Adaptive Outcomes of Microvascular Networks to Obesity and Type II Diabetes/Insulin Resistance” on July 30, 2016, at the Joint Meeting of the American Physiological Society and the Physiological Society, in Dublin, Ireland. We discuss the poor predictive power of traditional markers of vascular dysfunction for functional outcomes of muscle fatigue‐resistance and active hyperemia within the setting of elevated peripheral vascular disease risk. Using the obese Zucker rat model of the metabolic syndrome, we describe how blood flow distribution at arteriolar bifurcations (γ) is altered with PVD risk reflecting increased spatial heterogeneity of distribution within networks. The ability of the microvasculature to compensate for increased heterogeneity is attenuated in OZR, creating a condition wherein the inability to match perfusion to local demand is entrenched and made more difficult to overcome. This appears to be an incremental process, as multiple models of increased PVD risk manifest incremental shifts to the spatial and temporal behavior of γ. These data suggest that γ, a superior predictor of functional outcomes for skeletal muscle, may represent a broadly applicable concept that can inform us about system behavior, with health and increased disease/disease risk, and with imposition of therapeutic regimens.
Extracellular vesicles at the cross‐line between basic science and clinical needs
Authors: Sasso Luana , Hosamuddin Huma , Emanueli Costanza 
Published: November 2016

AbstractMiRNAs are small noncoding RNAs vital for protein regulation and gene expression. Since their discovery in the early nineties, many of their intracellular roles have been characterized. However, it is only recently that EVs loaded with miRNAs and other molecular types have started to be appreciated for their substantial involvement in cell‐to‐cell communication and signaling in physiological and pathological processes. EVs cell‐to‐cell signaling functions are complex and largely unknown, which still hampers the direct use of endogenous engineered EVs as therapeutics. However, ad hoc engineered synthetic EVs could represent new therapeutics. The potential of EV‐inspired delivery carriers has now attracted the interest of the pharmaceutical industry and has challenged drug delivery researchers with new questions. This review will focus on EVs and EV‐inspired drug delivery carriers, on their potential and on the challenges involved in the use of EV‐inspired drug delivery systems.
Evaluating the spore genome sizes of ferns and lycophytes: a flow cytometry approach
Authors: Kuo Li‐Yaung , Huang Yi‐Jia , Chang JenYu , Chiou Wen‐Liang , Huang Yao‐Moan 
Published: November 2016

Summary

Ferns and lycophytes produce spores to initiate the gametophyte stage for sexual reproduction. Approximately 10% of these seedless vascular plants are apomictic, and produce genomic unreduced spores. Genome size comparisons between spores and leaves are a reliable, and potentially easier way to determine their reproductive mode compared to traditional approaches. However, estimation of the spore genome sizes of these plants has not been attempted.

We attempted to evaluate the spore genome sizes of ferns and lycophytes using flow cytometry, collected spores from selected species representing different spore physical properties and taxonomic groups, and sought to optimize bead‐vortexing conditions. By evaluating the spore and sporophyte genome sizes, we examined whether reproductive modes could be ascertained from these flow cytometry results.

We proposed two separate sets of optimized bead‐vortexing conditions for the nuclear extraction of green and nongreen spores. We further successfully extracted spore nuclei of 19 families covering most orders, and the qualities and quantities of these extractions satisfied the C‐value criteria. These evaluated genome sizes further supported the reproductive modes reported previously.

In the current study, flow cytometry was used for the first time to evaluate the spore genome sizes of ferns and lycophytes. This use of spore flow cytometry provides a new, efficient approach to ascertaining the reproductive modes of these plants.
Validation of a male‐linked gene locus (OGI) for sex identification in persimmon (Diospyros kaki Thunb.) and its application in F1 progeny
Authors: Zhang Ping‐Xian , Yang Si‐Chao , Liu Yi‐Feng , Zhang Qing‐Lin , Xu Li‐Qing , Luo Zheng‐Rong 
Published: November 2016

AbstractIt is crucial to develop a rapid technique for identifying sexuality in the seedling stage of persimmon (Diospyros kaki Thunb.), and the elimination of male progeny has been regarded as an important strategy for enhancing breeding efficiency. In this study, phenotype characterization and genotyping of the male‐linked OGI marker were carried out using 205 accessions, including persimmon cultivars, F1 progeny and nine related Diospyros species. All persimmon cultivars displayed consistent results regarding OGI amplification and sex phenotype. A total of 143 F1 progeny were derived from 11 crosses, among which 95 individuals had flowered. In the flowering full‐sib families, the amplification of the OGI marker in agreement with the sex phenotype was obtained in 85 plants (89.5%). The segregation of OGI in ‘Huashi 1’ × ‘Luotian Tianshi’ and ‘Huashi 1’ × Male 3 F1 populations fit a 1 : 1 ratio. Furthermore, high OGI transferability was observed in nine related species. Overall, the results indicated that the OGI locus could be used to distinguish male from female persimmon plants at an early stage.
The potent pro‐oxidant activity of rhododendrol–eumelanin induces cysteine depletion in B16 melanoma cells
Authors: Ito Shosuke , Okura Masae , Wakamatsu Kazumasa , Yamashita Toshiharu 
Published: November 2016

SummaryRS‐4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, is known to induce leukoderma in some people. To explore the mechanism underlying this effect, we previously showed that the oxidation of RD with mushroom or human tyrosinase produces cytotoxic quinone oxidation products. We then examined the metabolism of RD in B16F1 melanoma cells in vitro and detected RD‐pheomelanin and RD‐quinone bound to non‐protein and protein thiols. In this study, we examined the changes in glutathione (GSH) and cysteine in B16 cells exposed to RD for up to 24 h. We find that the levels of cysteine, but not those of GSH, decrease during 0.5‐ to 3‐h exposure, due to oxidation to cystine. This pro‐oxidant activity was then examined using synthetic melanins. Indeed, we find that RD‐eumelanin exerts a pro‐oxidant activity as potent as Dopa‐pheomelanin. GSH, cysteine, ascorbic acid, and NADH were oxidized by RD‐eumelanin with a concomitant production of H2O2. We propose that RD‐eumelanin induces cytotoxicity through its potent pro‐oxidant activity.
Advocacy Coalitions in Ontario Land Use Policy Development
Authors: Timothy Heinmiller B. , Pirak Kevin 
Published: November 2016

AbstractIn 2005, the Ontario government passed the Places to Grow Act and the Greenbelt Act, both major changes in land use policy designed to preserve greenspaces and combat urban sprawl in the Greater Golden Horseshoe, Canada's largest conurbation. This article examines the actors, actor beliefs, and inter‐actor alliances in the southern Ontario land use policy subsystem from the perspective of the Advocacy Coalition Framework (ACF). Specifically, this paper undertakes an empirical examination of the ACF's Belief Homophily Hypothesis, which holds that inter‐actor alliances form on the basis of shared policy‐relevant beliefs, creating advocacy coalitions. The analysis finds strong evidence of three advocacy coalitions in the policy subsystem—an agricultural coalition, an environmentalist coalition, and a developers' coalition—as predicted by the hypothesis. However, it also finds equally strong evidence of a cross‐coalition coordination network of peak organizations, something not predicted by the Belief Homophily Hypothesis, and in need of explanation within the ACF.