bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species
Authors: Côco Hariane , Pernomian Larissa , Pereira Priscila C , Gomes Mayara S , Marchi Katia C , Lopes Alexandre H , Cunha Thiago M , Tirapelli Carlos R , de Oliveira Ana M 
Published: October 2016

Abstract

Objectives
To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.

Methods
Concentration–response curves for AngII were obtained in endothelium-intact or endothelium-denuded carotid rings, in the absence or presence of SC-560 (COX-1 inhibitor), SC-236 (COX-2 inhibitor), wortmannin (PI3K-Akt inhibitor), ML171 (NOX-1 inhibitor), VAS2870 (NOX-4 inhibitor), tiron (O2− scavenger) or PEG-catalase (H2O2 scavenger). 6-ketoPGF1α, TXB2, O2− or H2O2 levels and superoxide dismutase and catalase activity or expression were also measured in rat carotid.

Key findings
Stress increased AngII potency in rat carotid. Muscular COX-1 or COX-2-derived metabolites negatively modulated AngII-induced contraction in control rat carotid. Endothelial COX-1 or COX-2-derived metabolites positively modulated AngII-induced contraction in stressed rat carotid. PI3K-Akt, NOX-1, NOX-4, O2− and H2O2 positively modulated AngII-induced contraction in stressed rat carotid. Stress increased 6-ketoPGF1α or H2O2 generation and reduced catalase activity in rat carotid. Protein expression of COX-1, NOX-4 or p-Akt was increased in stressed rat carotid.

Conclusions
Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI2 and H2O2 and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.
Phenolic compounds alone or in combination may be involved in propolis effects on human monocytes
Authors: Cardoso Eliza de Oliveira , Conti Bruno José , Santiago Karina Basso , Conte Fernanda Lopes , Oliveira Lucas Pires Garcia , Hernandes Rodrigo Tavanelli , Golim Marjorie de Assis , Sforcin José Maurício 
Published: October 2016

Abstract

Objectives
Propolis is a natural product with a complex chemical composition. Its isolated compounds exert biological activities; however, its synergistic effects are unknown. The involvement of phenolic acids (caffeic – Caf, dihydrocinnamic – Cin and p-coumaric – Cou) alone or in combination was investigated in the action of propolis in human monocytes.

Methods
Cell viability was analysed by MTT assay; TNF-α, IL-6 and IL-10 production by enzyme-linked immunosorbent assay (ELISA); cell markers expression by flow cytometry; colony-forming units were counted to assess the microbicidal activity; and H2O2 production was analysed by colorimetric assay.

Key findings
Treatments did not affect monocytes viability. Propolis and combinations containing Caf enhanced TNF-α production by resting cells. Propolis, Cin, Cou and Caf + Cin stimulated IL-6 production. All treatments upregulated IL-10. In LPS-stimulated cells, treatments downregulated IL-6 and maintained TNF-α and IL-10 production. A lower TLR-2 expression was seen than propolis. Caf + Cin enhanced TLR-4 expression. Propolis, Caf and Caf + Cin stimulated H2O2 production, whereas propolis, Cin, Cou, and Caf + Cin + Cou induced a higher fungicidal activity. Cin and Cin + Cou increased the bactericidal activity of human monocytes.

Conclusion
Propolis activated human monocytes, and acids were involved differently in propolis activity.
Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery
Authors: Rahman Mahfoozur , Beg Sarwar , Verma Amita , Al Abbasi Fahad A , Anwar Firoz , Saini Sumant , Akhter Sohail , Kumar Vikas 
Published: October 2016

Abstract

Objectives
The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed.

Key findings
Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kβ, lipoxygenase (LOXs) and arachidonic acid (AA). Despite the presence of significant merits, the use of these bioactives has several demerits such as poor bioavailability as a function of low aqueous solubility and higher first-pass metabolism upon oral administration. The impact of nano/submicromedicine in the delivery of these bioactives against RA has gained wider attention owing to bioavailability enhancement, higher stability and better efficacy.

Conclusion
Phytoconstituents possess immense potential in RA pharmacotherapy, but the obstacles for their effective delivery can be overcome using nano/submicrocarrier-based drug delivery technologies, which maximize the efficacy of these herbal antirheumatic drugs without any systemic adverse effects.
The role of drug efflux pumps in Malassezia pachydermatis and Malassezia furfur defence against azoles
Authors: Iatta Roberta , Puttilli Maria Rita , Immediato Davide , Otranto Domenico , Cafarchia Claudia 
Published: October 2016

SummaryThis study aims to evaluate the effect of efflux pump modulators (EPMs) on the minimal inhibitory concentration (MIC) of fluconazole (FLZ) and voriconazole (VOR) in Malassezia furfur and Malassezia pachydermatis. The in vitro efficacy of azoles, in combination with EPMs (ie haloperidol‐HAL, promethazine‐PTZ and cyclosporine A‐CYS), against 21 M. furfur from bloodstream infection patients and 14 M. pachydermatis from the skin of dogs with dermatitis, was assessed using a broth microdilution chequerboard analysis. Data were analysed using the model‐fractional inhibitory concentration index (FICI) method. The MIC of FLZ and VOR of Malassezia spp. decreased in the presence of sub‐inhibitory concentrations of HAL and/or PTZ. The synergic effect was observed only in strains with FLZ MIC≥128 μg/mL for M. furfur, FLZ MIC≥64 μg/mL for M. pachydermatis and VOR MIC≥4 μg/mL in both Malassezia spp. These results suggest that the drug efflux pumps are involved as defence mechanisms to azole drugs in Malassezia yeast. The synergism might be related to an increased expression of efflux pump genes, eventually resulting in azole resistance phenomena. Finally, the above FLZ and VOR MIC values might be considered the cut‐off to discriminate susceptible and resistant strains.
Epistemic Normativity and Cognitive Agency
Authors: Chrisman Matthew 
Published: October 2016

AbstractOn the assumption that genuinely normative demands concern things connected in some way to our agency, i.e. what we exercise in doing things with or for reasons, epistemologists face an important question: are there genuine epistemic norms governing belief, and if so where in the vicinity of belief are we to find the requisite cognitive agency? Extant accounts of cognitive agency tend to focus on belief itself or the event of belief‐formation to answer this question, to the exclusion of the activity of maintaining a system of beliefs. This paper argues that a full account of epistemic normativity will need to make sense of this activity as a core locus of cognitive agency. This idea is used to motivate the conclusion that one important and often overlooked kind of epistemic norms is the kind of norms governing the various cognitive activities by which we check, sustain, and adjust our belief systems.
Ethylene and nitric oxide interact to regulate the magnesium deficiency‐induced root hair development in Arabidopsis
Authors: Liu Miao , Liu Xing Xing , He Xiao Lin , Liu Li Juan , Wu Hao , Tang Cai Xian , Zhang Yong Song , Jin Chong Wei 
Published: October 2016

Summary

Nitric oxide (NO) and ethylene respond to biotic and abiotic stresses through either similar or independent processes. This study examines the mechanism underlying the effects of NO and ethylene on promoting root hair development in Arabidopsis under magnesium (Mg) deficiency.

The interaction between NO and ethylene in the regulation of Mg deficiency‐induced root hair development was investigated using NO‐ and ethylene‐related mutants and pharmacological methods.

Mg deficiency triggered a burst of NO and ethylene, accompanied by a stimulated development of root hairs. Interestingly, ethylene facilitated NO generation by activation of both nitrate reductase and nitric oxide synthase‐like (NOS‐L) in the roots of Mg‐deficient plants. In turn, NO enhanced ethylene synthesis through stimulating the activities of 1‐aminocyclopropane‐1‐carboxylate (ACC) oxidase and ACC synthase (ACS). These two processes constituted an NO‐ethylene feedback loop. Blocking either of these two processes inhibited the stimulation of root hair development under Mg deficiency.

In conclusion, we suggest that Mg deficiency increases the production of NO and ethylene in roots, each influencing the accumulation and role of the other, and thus these two signals interactively regulate Mg deficiency‐induced root hair morphogenesis.
Obesogens and male fertility
Authors: Cardoso A. M. , Alves M. G. , Mathur P. P. , Oliveira P. F. , Cavaco J. E. , Rato L. 
Published: October 2016

SummaryIn the last decades, several studies evidenced a decrease in male fertility in developed countries. Although the aetiology of this trend in male reproductive health remains a matter of debate, environmental compounds that predispose to weight gain, namely obesogens, are appointed as contributors because of their action as endocrine disruptors. Obesogens favour adipogenesis by an imbalance of metabolic processes and can be found virtually everywhere. These compounds easily accumulate in tissues with high lipid content. Obesogens change the functioning of male reproductive axis, and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. Notably, adverse effects of obesogens may also promote disturbances in the metabolic performance of the following generations, through epigenetic modifications passed by male gametes. Thus, unveiling the molecular pathways by which obesogens induce toxicity that may end up in epigenetic modifications is imperative. Otherwise, a transgenerational susceptibility to metabolic diseases may be favoured. We present an up‐to‐date overview of the impact of obesogens on testicular physiology, with a particular focus on testicular metabolism. We also address the effects of obesogens on male reproductive parameters and the subsequent consequences for male fertility.
Does the Badal optometer stimulate accommodation accurately?
Authors: Aldaba Mikel , Otero Carles , Pujol Jaume , Atchison David A. 
Published: October 2016

AbstractPurposeTo study whether the accommodation response to Badal optometer is equivalent to the response for real space targets.MethodsAccommodative responses were measured for 28 young eyes with the WAM‐5500 autorefractometer in eight configurations for 0.17 D, 2.0 D and 5.0 D accommodation stimuli. Parameters that might contribute to differences in response were systematically isolated: stimulation method (real space vs Badal targets), field of view, instrument's cover proximity, the looming effect, and the peripheral interposition of objects in depth.ResultsMean accommodative response differences between a natural view configuration and a configuration with a Badal Optometer were 0.50 ± 0.43 D and 0.58 ± 0.53 D for 2.0 D and 5.0 D stimulation, respectively (p < 0.001), with accommodation lags for the latter condition. Of the isolated parameters that might contribute to these differences, varying the interposition of objects in depth affected accommodation response more markedly.ConclusionsIt is likely that Badal optometers affect accommodation through a combination of some or all of the studied parameters. We conclude that accommodation response to closed‐view Badal optometers is not equivalent to real space target response.
Overexpression of the 16‐kDa α‐amylase/trypsin inhibitor RAG2 improves grain yield and quality of rice
Authors: Zhou Wei , Wang Xin , Zhou Dan , Ouyang Yidan , Yao Jialing 
Published: October 2016

SummaryIncreasing grain yield and improving grain quality are two important goals for rice breeding. A better understanding of the factors that contribute to the overall grain quantity and nutritional quality of rice will lay the foundation for developing new breeding strategies. RAG2 is a member of 14‐to‐16‐kDa α‐amylase/trypsin inhibitors in rice, which belong to the albumin of seed storage proteins. We found that RAG2 was specifically expressed in ripening seed and its transcription peak was between 14 and 21 days after flowering. Grain size and 1000‐grain weight were obviously increased in RAG2‐overexpressed lines compared with wild type, and grain size was reduced in RAG2‐suppressed lines. In addition, the major storage substances of the seeds differed significantly in RAG2‐overexpressed and RAG2‐suppressed lines compared to wild type. The protein content and amount of total lipids were increased and decreased, respectively, in the seeds of RAG2‐overexpressed and RAG2‐suppressed lines. Overexpression of RAG2 significantly increased grain size and improved grain quality and yield simultaneously. These results imply that RAG2 might play an important role in regulating grain weight and seed quality of rice. The functional characterization of rice RAG2 facilitates a further understanding of the mechanisms involved in grain size and seed quality and may be helpful in improving grain yield and quantity in cereal crops.
Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity
Authors: Dolinska Monika B. , Kus Nicole J. , Farney S. Katie , Wingfield Paul T. , Brooks Brian P. , Sergeev Yuri V. 
Published: October 2016

SummaryOculocutaneous albinism type 1 (OCA1) is an autosomal recessive disorder caused by mutations in the tyrosinase gene. Two subtypes ofOCA1 have been described: severeOCA1A with complete absence of tyrosinase activity and less severeOCA1B with residual tyrosinase activity. Here, we characterize the recombinant human tyrosinase intramelanosomal domain and mutant variants, which mimic genetic changes in both subtypes ofOCA1 patients. Proteins were prepared using site‐directed mutagenesis, expressed in insect larvae, purified by chromatography, and characterized by enzymatic activities, tryptophan fluorescence, and Gibbs free energy changes. TheOCA1A mutants showed very low protein expression and protein yield and are enzymatically inactive. Mutants mimickingOCA1B were biochemically similar to the wild type, but exhibited lower specific activities and protein stabilities. The results are consistent with clinical data, which indicates thatOCA1A mutations inactivate tyrosinase and result in severe phenotype, whileOCA1B mutations partially inactivate tyrosinase and result inOCA1B albinism.
The histological quantification of alpha‐smooth muscle actin predicts future graft fibrosis in pediatric liver transplant recipients
Authors: Varma Sharat , Stéphenne Xavier , Komuta Mina , Bouzin Caroline , Ambroise Jerome , Smets Françoise , Reding Raymond , Sokal Etienne M. 
Published: October 2016

AbstractActivated hepatic stellate cells express cytoplasmic ASMA prior to secreting collagen and consequent liver fibrosis. We hypothesized that quantifying ASMA could predict severity of future fibrosis after LT. For this, 32 pairs of protocol biopsies, that is, “baseline” and “follow‐up” biopsies taken at 1‐ to 2‐year intervals from 18 stable pediatric LT recipients, transplanted between 2006 and 2012 were selected. Morphometric quantification of “ASMA‐positive area percentage” was performed on the baseline biopsy. Histological and fibrosis assessment using Metavir and LAFSc was performed on all biopsies. The difference of fibrosis severity between the “baseline” and “follow‐up” was termed “prospective change in fibrosis.” Significant association was seen between extent of ASMA positivity on baseline biopsy and “prospective change in fibrosis” using Metavir (P=.02), cumulative LAFSc (P=.02), and portal LAFSc (P=.01) values. ASMA‐positive area percentage >1.05 predicted increased fibrosis on next biopsy with 90.0% specificity. Additionally, an association was observed between extent of ASMA positivity and concomitant ductular reaction (P=.06), but not with histological inflammation in the portal tract or lobular area. Hence, ASMA quantification can predict the future course of fibrosis.
Characterising genes associated with flowering time in carrot (Daucus carota L.) using transcriptome analysis
Authors: Ou C.‐G. , Mao J.‐H. , Liu L.‐J. , Li C.‐J. , Ren H.‐F. , Zhao Z.‐W. , Zhuang F.‐Y. 
Published: October 2016

Abstract

Carrot is generally regarded as a biennial plant with an obligatory vernalization requirement. Early spring cultivation makes plants vulnerable to premature bolting, which results in a loss of commercial value. However, our knowledge of flowering time genes and flowering mechanisms in carrot remain limited.

Bolting behavior of D. carota ssp. carota ‘Songzi’, a wild species sensitive to flower induction by vernalization and photoperiod, and orange cultivar ‘Amsterdam forcing’, and their offspring were investigated in different growing conditions. We performed RNA‐seq to identify the flowering time genes, and digital gene expression (DGE) analysis to examine their expression levels. The circadian patterns of related genes were identified by qPCR.

The results showed bolting behavior of carrot was influenced by low temperature, illumination intensity and photoperiod. A total of 45 flowering time‐related unigenes were identified, which were classified into five categories including photoperiod, vernalization, autonomous and gibberellin pathway, and floral integrators. Homologs of LATE ELONGATED HYPOCOTYL (LHY) and CONSTANS‐LIKE 2 (COL2) were more highly expressed under short day condition than under long day condition. Homologs of COL2, CONSTANS‐LIKE 5 (COL5), SUPPRESSION OF OVEREXPRESSION OF CONSTANS 1 (SOC1), FLOWERING LOCUS C (FLC) and GIBBERELLIC ACID INSENSITIVE (GAI) were differentially expressed between ‘Songzi’ and ‘Amsterdam forcing’. The homolog of COL2 (Dct43207) was repressed by light, but that of COL5 (Dct20940) was induced. A preliminary model of genetic network controlling flowering time was constructed by associating the results of DGE analysis with correlation coefficients between genes.

This study provides useful information for further investigating the genetic mechanism of flowering in carrot.
Morbidity and Health Care Costs After Early Term Birth
Authors: Helle Emmi , Andersson Sture , Häkkinen Unto , Järvelin Jutta , Eskelinen Janne , Kajantie Eero 
Published: October 2016

AbstractBackgroundEarly term birth is associated with increased need for hospital care during the early postnatal period. The objective of this study was to assess the morbidity and health care‐related costs during the first 3 years of life in children born early term.MethodsData come from a population‐based birth cohort study in the municipalities of Helsinki, Espoo, and Vantaa, Finland using data from the national medical birth register and outpatient, inpatient, and primary care registers. All surviving infants born in 2006–08 (n = 29 970) were included. The main outcome measures were morbidities, based on ICD‐10 codes recorded during inpatient and outpatient hospital visits, and health care costs, based on all care received, including well child visits (specialised care, primary care, private care, and medications).Results7.0% of children born full term had at least one of the studied morbidities by 3 years of age. This percentage was significantly higher in children born early term: 8.6% (adjusted odds ratio 1.2, 95% confidence interval (CI) 1.1, 1.4). The increased morbidity of children born early term was attributed to obstructive airway diseases and ophthalmological and motor problems. Health care‐related costs during the first 3 years of life were 4813€ (95% CI 4385, 5241) per child in the early term group, higher than for full term children 4047€ (95% CI 3884, 4210).ConclusionsInfants born early term have increased morbidity and higher health care‐related costs during early childhood than full term infants. Early term birth seems to be associated with a health disadvantage.
Characterization of teratogenic potential and gene expression in canine and feline amniotic membrane‐derived stem cells
Authors: Cardoso MT , Pinheiro AO , Vidane AS , Casals JB , de Oliveira VC , Gonçalves NJN , Martins DS , Ambrósio CE 
Published: October 2016

ContentsThe biosafety of innovative procedures that utilize stem cells in regenerative medicine has been addressed in several studies. Previous work has showed no tumour formation following the use of feline and human amniotic membrane‐derived stem cells (AMSCs). In contrast, tumour formation was observed when canine AMSCs were utilized. These findings suggested that feline and human, but not canine, AMSCs are suitable for cell transplantation trials. This study aimed to further evaluate the feasibility of utilizing canine AMSCs for transplantation purposes as well as for felines. We tested teratoma formation following cell injection into BALB/c nude mice and then assessed expression of haematopoietic, mesenchymal, tumorigenic, pluripotency and cellular regulation markers using flow cytometry and qPCR. The use of canine AMSCs did not result in macroscopic tumour formation as determined 60 days after transplantation. The immunophenotypic characterization by flow cytometry revealed expression of mesenchymal markers (CD73 and CD90) and expression of the pluripotent marker OCT4 and SOX2. Quantitative PCR analysis revealed that there were no differences in the patterns of gene expression (CD34, CD73, OCT4, CD30 and P53) between canine and feline AMSCs, with the exception of the expression of SOX2 and CD90.
Unified Inference for Sparse and Dense Longitudinal Data in Time‐varying Coefficient Models
Authors: Chen Yixin , Yao Weixin 
Published: October 2016

AbstractTime‐varying coefficient models are widely used in longitudinal data analysis. These models allow the effects of predictors on response to vary over time. In this article, we consider a mixed‐effects time‐varying coefficient model to account for the within subject correlation for longitudinal data. We show that when kernel smoothing is used to estimate the smooth functions in time‐varying coefficient models for sparse or dense longitudinal data, the asymptotic results of these two situations are essentially different. Therefore, a subjective choice between the sparse and dense cases might lead to erroneous conclusions for statistical inference. In order to solve this problem, we establish a unified self‐normalized central limit theorem, based on which a unified inference is proposed without deciding whether the data are sparse or dense. The effectiveness of the proposed unified inference is demonstrated through a simulation study and an analysis of Baltimore MACS data.