bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid droplet distribution of immature canine oocytes in relation to their size and the reproductive stage
Authors: Ariu Federica , Strina Alessandro , Murrone Ombretta , Falchi Laura , Bebbere Daniela , Ledda Sergio , Zedda Maria Teresa , Pau Salvatore , Bogliolo Luisa 
Published: September 2015

AbstractThis study investigated the distribution of lipid droplets (LD) in immature canine oocytes in relation to their size and the reproductive stage. Oocytes were collected from the ovaries of bitches at different estrous stages, divided according to their size (110‐120 µm; >120 µm), and stained with Nile Red to detect lipid droplet distribution. At the follicular phase most of the oocytes displayed a diffuse pattern of LD distribution, whereas at anestrus and luteal phase oocytes showed LD mainly in a peripheral/ perinuclear LD distribution. A significantly higher intensity of LD has been recorded in the oocytes > 120 µm compared to those of smaller size (110 ‐ 120 µm) at all stages of the estrous cycle. At follicular phase, oocytes > 120 µm displayed LD intensity similar to that of oocytes > 120 µm at luteal phase and higher compared to the oocytes of the other groups.
Correlated response of peripheral blood cytokines with selection for reduced mycoplasma pneumonia of swine lesions in Landrace pigs
Authors: Sato Takumi , Okamura Toshihiro , Kojima‐Shibata Chihiro , Kadowaki Hiroshi , Suzuki Eisaku , Uenishi Hirohide , Suzuki Keiichi 
Published: October 2015

AbstractMycoplasma pneumonia of swine (MPS) is responsible for significant economic losses in the swine industry. We selected Landrace pigs for reduced MPS pulmonary lesions over five generations, and measured concentrations of the following cytokines: interleukin (IL)‐10, IL‐13, IL‐17, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ to estimate their correlation with MPS lesions. Sheep red blood cells (SRBC) were injected twice intramuscularly at 70 and 95 kg body weight. Blood serum samples were collected after 1 week of secondary SRBC inoculation and cytokine concentrations were analyzed by ELISA. Genetic parameters and breeding values were estimated. The heritability estimates of IL‐10, IL‐13, IL‐17, TNF‐α and IFN‐γ were 0.20 ± 0.06, 0.12 ± 0.06, 0.27 ± 0.07, 0.20 ± 0.10 and 0.05 ± 0.03, respectively. Genetic correlations of IL‐17 and TNF‐α with pulmonary MPS lesions were high (‐0.86 ± 0.13 and 0.69 ± 0.29, respectively) and those of IFN‐γ and IL‐13 with MPS lesions were moderately negative (‐0.45). Through selection, the breeding values of IL‐17 and IFN‐γ increased substantially and those of TNF‐α decreased. These results suggest that innate and cellular immunity are more important for the suppression of pulmonary lesions in MPS than humoral‐mediated immunity, such as antibody response.
The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes
Authors: Kim Ho‐Sook , Lim Younghae , Oh Minkyung , Ghim Jong‐lyul , Kim Eun‐Young , Kim Dong‐Hyun , Shin Jae‐Gook 
Published: October 2015

AimThe primary objective of the present study was to evaluate the pharmacokinetic and pharmacodynamic interactions between clopidogrel and cilostazol in relation to the CYP2C19 and CYP3A5 genotypes.MethodsIn a randomized, three‐way crossover study, 27 healthy subjects were administered clopidogrel (300 mg), cilostazol (100 mg) or clopidogrel + cilostazol orally. Plasma concentrations of clopidogrel, cilostazol and their active metabolites (clopidogrel thiol metabolite, 3,4‐dehydrocilostazol and 4″‐trans‐hydroxycilostazol), and adenosine diphosphate‐induced platelet aggregation were measured for pharmacokinetic and pharmacodynamic assessment.ResultsThe area under the plasma concentration–time curve (AUC) of the active thiol metabolite of clopidogrel was highest in the CYP2C19 extensive metabolizers (EM) and lowest in the poor metabolizers (PM). Cilostazol decreased the thiol metabolite AUC by 29% in the CYP3A5*1/*3 genotype [geometric mean ratio (GMR) 0.71; 90% confidence interval (CI) 0.58, 0.86; P = 0.020] but not in the CYP3A5*3/*3 genotype (GMR 0.93; 90% CI 0.80, 1.10; P = 0.446).Known effects of the CYP2C19 and CYP3A5 genotypes on the exposure of cilostazol and its metabolites were observed but there was no significant difference in the AUC of cilostazol and 3,4‐dehydrocilostazol between cilostazol and clopidogrel + cilostazol.The inhibition of platelet aggregation from 4 h to 24 h (IPA4–24) following the administration of clopidogrel alone was highest in the CYP2C19 EM genotype and lowest in the CYP2C19 PM genotype (59.05 ± 18.95 vs. 36.74 ± 13.26, P = 0.023). However, the IPA of the CYP2C19 PM following co‐administration of clopidogrel and cilostazol was comparable with that of the CYP2C19 EM and intermediate metabolizers (IM) only in CYP3A5*3/*3 subjects.ConclusionsThe additive antiplatelet effect of cilostazol plus clopidogrel is maximized in subjects with both the CYP2C19 PM and CYP3A5*3/*3 genotypes because of a lack of change of clopidogrel thiol metabolite exposure in CYP3A5*3/*3 as well as the highest cilostazol IPA in CYP2C19 PM and CYP3A5*3/*3 subjects.
Synthesis, Biological Evaluation, and Molecular Docking of (R)‐2‐((8‐(3‐aminopiperidin‐1‐yl)‐3‐methyl‐7‐(3‐methylbut‐2‐en‐1‐yl)‐2,6‐dioxo‐2,3,6,7‐tetrahydro‐1H‐purin‐1‐yl)methyl)benzonitrile as Dipeptidyl Peptidase IV Inhibitors
Authors: Ran Yan , Pei Heying , Shao Mingfeng , Chen Lijuan 
Published: October 2015

Type 2 diabetes (T2D) is classified as a major metabolic disorder, which has affected approximately 194 million people worldwide. DPP‐IV inhibitors as a new therapy have shown several advantages over traditional antidiabetic drugs. Based on the similar binding modes of Alogliptin and Linagliptin, molecular operation was conducted via combining pharmacophore hybridization with structural optimization between the two market drugs and racemic compounds 40 and 43 were reported as DPP‐IV inhibitors in our previous studies. But the majority of DPP‐IV inhibitors have developed into a small molecule with certain conformation; in this study, we described the synthesis, biological evaluation, and molecular docking of corresponding enantiomers of compounds 40 and 43. The most potent inhibitor is (R)‐40 (IC50 = 23.5 nm, F = 74.67%, T1/2 = 4 h), which exhibited moderate antihyperglycemic activity as compared to the standard antidiabetic drug Linagliptin in OGTT. In addition, compound (R)‐40 effectively improved the pathological state of DIO mice. Molecular docking studies clarified the favorable binding affinity between compound (R)‐40 and DPP‐IV active site. Thus, compound (R)‐40 would be entitled to further development as a drug candidate on the basis of the suitable pharmacokinetic (PK) and desirable pharmacodynamic (PD) profiles.
Sexual function and depressive symptoms in young women with thyroid autoimmunity and subclinical hypothyroidism
Authors: Krysiak Robert , Drosdzol‐Cop Agnieszka , Skrzypulec‐Plinta Violetta , Okopien Bogusław 
Published: October 2015

SummaryObjectiveThe results of few studies conducted to date suggest an increased prevalence of sexual dysfunction in patients with thyroid disorders.DesignThe aim of this study was to compare female sexual function and depressive symptoms between women with autoimmune thyroid disease and with mild thyroid failure.PatientsThe study included four groups of young women: euthyroid women with Hashimoto's thyroiditis (Group 1), women with nonautoimmune subclinical hypothyroidism (Group 2), women with autoimmune subclinical hypothyroidism (Group 3) and healthy euthyroid females without thyroid autoimmunity (Group 4).MeasurementsBeyond measuring serum hormone levels and thyroid antibody titres, all enrolled women completed questionnaires evaluating female sexual function (Female Sexual Function Index – FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory‐Second Edition – BDI‐II).ResultsThe mean total FSFI score was lower in women with autoimmune hypothyroidism than in the remaining groups of women, as well as lower in Groups 1 and 2 than in Group 4. Compared to Group 4, three domains (sexual desire, lubrication and sexual satisfaction) were lower in Group 1, four domains (desire, arousal, lubrication and dyspareunia) in Group 2 and all FSFI domain scores in Group 3. The total BDI‐II score was higher in Groups 1 and 2 than in Group 4, as well as higher in Group 3 than in the other groups of women.ConclusionsThe obtained results suggest that both thyroid autoimmunity and mild thyroid failure, particularly if they occur together, may negatively affect female sexual function and depressive symptoms.
Association between left ventricular mass, androgens, adiposity and insulin resistance in girls with precocious pubarche: a case–control study
Authors: Satler Fabíola , Vieira Raquel do Amaral , Firpo Cora , Spritzer Poli Mara 
Published: October 2015

SummaryObjectivePrecocious pubarche (PP) has been linked to higher prevalence of metabolic disturbances and polycystic ovary syndrome (PCOS). The aim of the study was to assess echocardiographic parameters in PP girls and to analyse their relationship with androgens and insulin resistance (IR).DesignCase–control study.PatientsThirty‐five PP girls and 35 healthy age‐matched controls.MeasurementsClinical, hormonal and metabolic profiles, echocardiography, body composition and oral glucose tolerance test.ResultsChronological age (10·04 ± 2·6 years in PP vs 10·13 ± 2·56 years in controls, P = 0·227), and pubertal stage at the time of the study were similar between the groups. PP girls had higher free androgen index (FAI) [1·39 (0·48–3·64) vs 1·06 (0·39–1·7), P = 0·005] and QUICKI (0·58 ± 0·08 vs 0·63 ± 0·12, P = 0·021). However, HOMA‐IR was not significantly different between the groups [2·79 (1·84–4·05) vs 2·15 (1·09–3·23), P = 0·085]. After adjusting for total body fat, left ventricular mass (LVM) was higher in the PP group (97·31 ± 33·37 vs 81·25 ± 19·06 g, P = 0·017) as well as A′ wave (5·66 ± 1·34 vs 5·09 ± 0·98 cm/s, P = 0·025), a measurement of diastolic function. FAI and total body fat were independent predictors of higher LVM and together with HOMA‐IR contributed 72% of LVM variability in the PP group.ConclusionIn this study with PP girls, greater LVM, associated with higher androgen levels, IR and total body fat, occurred early in pubertal development.
Insulin resistance and composite indices of femoral neck strength in Asians: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV)
Authors: Ahn Seong Hee , Kim Hyeonmok , Kim Beom‐Jun , Lee Seung Hun , Koh Jung‐Min 
Published: October 2015

SummaryObjectiveFracture risk in type 2 diabetes mellitus with insulin resistance is increased, despite relatively preserved bone mineral density (BMD). In this study, we investigated the relationship between insulin resistance and composite indices of femoral neck strength in Koreans.DesignA population‐based, cross‐sectional study from the Korea National Health and Nutrition Examination SurveyParticipantsAbout 1243 men and 1433 womenMeasurementsInsulin resistance was evaluated using the homoeostasis model assessment‐estimated insulin resistance (HOMA‐IR) index. Femoral neck width and axis length were measured from hip dual‐energy X‐ray absorptiometry scans and combined with BMD, weight and height to calculate composite indices of femoral neck strength relative to load: compression (CSI), bending (BSI) and impact strength indices (ISI).ResultsHOMA‐IR showed an inverse relationship with CSI, BSI and ISI in both genders before and after adjusting for confounders (P < 0·001–0·029). CSI was more strongly associated with HOMA‐IR than BSI and/or ISI in both genders (P < 0·001–0·013). When men were stratified according to HOMA‐IR quartiles, all strength indices decreased as the quartile increased, after adjusting for all potential confounders (P for trend <0·001–0·001), whereas CSI and ISI did in women (P for trend = 0·012 and 0·002, respectively). Fasting insulin levels, but not glucose levels, were negatively associated with all strength indices regardless of confounders (P < 0·001–0·044).ConclusionsInsulin resistance is associated with low femoral neck strength, particularly against the compressive load. These findings suggest a better approach to evaluate bone health in insulin‐resistant individuals.
Protein biomarkers and microbial profiles in peri‐implantitis
Authors: Wang Hom‐Lay , Garaicoa‐Pazmino Carlos , Collins Amy , Ong Hwen‐Sei , Chudri Rini , Giannobile William V. 
Published: October 2015

AbstractObjectivesThe aim of the present investigation was to determine the profile of peri‐implant crevicular fluid (PICF) biomarkers combined with microbial profiles from implants with healthy peri‐implant tissues and peri‐implantitis to assess real‐time disease activity.Material and methodsSixty‐eight patients were included in this cross‐sectional study. They were divided into two groups: 34 patients with at least one healthy implant (control) and 34 with at least one peri‐implantitis affected implant (test). Total DNA content and qPCR analysis for periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL‐1β, VEGF, MMP‐8, TIMP‐2, and OPG were performed. The individual and combined diagnostic ability of each biomarker for peri‐implantitis and target bacterial species were analyzed.ResultsThe mean concentration of IL‐1β (44.6 vs. 135.8 pg/ml; P < 0.001), TIMP‐2 (5488.3 vs. 9771.8 pg/ml; P = 0.001), VEGF (59.1 vs. 129.0 pg/ml; P = 0.012), and OPG (66.5 vs. 111.7 pg/ml; P = 0.050) was increased in the peri‐implantitis patients. The mean expression of MMP‐8 (6029.2 vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among groups. Total bacterial DNA of selected microorganisms was associated with a threefold or greater increase in peri‐implantitis although no statistical significant difference. The ability to diagnose diseased sites was enhanced by T. denticola combined with IL‐1β, VEGF, and TIMP‐2 PICF levels.ConclusionThe present data suggest that the increased levels of the selected PICF‐derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site‐specific microbial profiles may be associated with peri‐implantitis and could have potential as predictors of peri‐implant diseases.
Growth, development, and life‐history strategies in an unpredictable environment: case study of a rare hoverfly Blera fallax (Diptera, Syrphidae)
Authors: ROTHERAY ELLEN L. , GOULSON DAVE , BUSSIÈRE LUC F. 
Published: October 2015

1. Development in organisms can vary in response to fluctuating environments. In holometabolous insects, variation in adult phenotypic traits is strongly influenced by growth conditions experienced by larvae. The main aim of this study was to assess how much environmental insight can be gained from analysis of the phenotypic changes in an insect's life history parameters in response to realistic food limitations.2. This investigation was motivated by a need for more information about the developmental requirements of the endangered pine hoverfly Blera fallax (Linnaeus) (Diptera, Syrphidae) in Scotland. Blera fallax depends on a scarce and often ephemeral habitat, rot holes of Scots pine Pinus sylvestris L. stumps. We studied how rearing conditions affected growth in captive larvae, and compared these responses with a wild population.3. The growth curve observed in the field was similar to that in resource‐limited, lab conditions, suggesting that resources are limiting in nature. The effects of resource availability on development time and body size depended on sex. Adult females were larger but had more variable size at maturity compared with males. In contrast, males typically were not smaller in resource‐limited conditions, but rather continued to develop for another year. Between 2% and 20% of larvae extended development over 2 years regardless of growth conditions, perhaps indicating a semivoltine strategy to circumvent extinction during years with a low breeding success.4. These results identify life history traits that may be important for other saproxylic Diptera in rot holes, and organisms that experience food restrictions during growth.
A consensus review on the development of palliative care for patients with chronic and progressive neurological disease
Authors: Oliver D. J. , Borasio G. D. , Caraceni A. , de Visser M. , Grisold W. , Lorenzl S. , Veronese S. , Voltz R. 
Published: October 2015

Background and purposeThe European Association of Palliative Care Taskforce, in collaboration with the Scientific Panel on Palliative Care in Neurology of the European Federation of Neurological Societies (now the European Academy of Neurology), aimed to undertake a review of the literature to establish an evidence‐based consensus for palliative and end of life care for patients with progressive neurological disease, and their families.MethodsA search of the literature yielded 942 articles on this area. These were reviewed by two investigators to determine the main areas and the subsections. A draft list of papers supporting the evidence for each area was circulated to the other authors in an iterative process leading to the agreed recommendations.ResultsOverall there is limited evidence to support the recommendations but there is increasing evidence that palliative care and a multidisciplinary approach to care do lead to improved symptoms (Level B) and quality of life of patients and their families (Level C). The main areas in which consensus was found and recommendations could be made are in the early integration of palliative care (Level C), involvement of the wider multidisciplinary team (Level B), communication with patients and families including advance care planning (Level C), symptom management (Level B), end of life care (Level C), carer support and training (Level C), and education for all professionals involved in the care of these patients and families (Good Practice Point).ConclusionsThe care of patients with progressive neurological disease and their families continues to improve and develop. There is a pressing need for increased collaboration between neurology and palliative care.
European Roe Deer Increase Vigilance When Faced with Immediate Predation Risk by Eurasian Lynx
Authors: Eccard Jana A. , Meißner Jessica K. , Heurich Marco 
Published: October 2015

AbstractPrey animals must balance antipredatory behaviour with foraging behaviour. According to the risk allocation hypothesis, prey increase antipredatory behaviour and reduce foraging activity during pulses of high risk, but with continuous risk, other activities must continue and antipredatory behaviour decreases despite the risk. We studied the impact of lynx presence on the vigilance behaviour of wild roe deer under conditions of (i) a pulsed elevated risk by experimentally spreading lynx urine as an olfactory cue, and (ii) continuous risk by comparing an area where lynx was eradicated 160 years ago to an area where lynx has been re‐introduced 30 years ago. Roe deer were extremely vigilant in response to the predator olfactory cue; however, roe deer vigilance did not differ measurably among areas with or without potential lynx presence. Deer were more vigilant before sunset than during the night at both study areas, probably due to long‐term adaptation of roe deer to human hunting during daytime. Vigilance decreased from August to September even though activity of lynx increases in autumn, which may be a result either of increased foraging due to decrease in food quality in autumn, or of changes in social organization of the deer. Our results suggested that the degree of vigilance depends on environmental cues. We found that roe deer respond to lynx urine despite a long absence of lynx in the ecosystem. Our results support the risk allocation hypothesis for responses to pulses of high risk but not for responses to continuous elevated levels of risk.
The Oxidative Cost of Acoustic Signals: Examining Steroid Versus Aerobic Activity Hypotheses in a Wild Bird
Authors: Baldo Sarah , Mennill Daniel J. , Guindre‐Parker Sarah , Gilchrist Hugh Grant , Love Oliver P. 
Published: October 2015

AbstractVertebrate vocalizations are widespread secondary sexual signals used for mate attraction and territory defence, and variation in signal quality is often condition dependent and impacts reproductive outcomes. Although vocal signal performance is known to reflect various aspects of male quality, few studies have examined the underlying mechanisms mediating its costs and hence its honesty. Using a population of Arctic‐breeding snow buntings (Plectrophenax nivalis), we compared the ‘Oxidation Handicap Hypothesis’, which predicts that testosterone‐induced increases in oxidative stress provide a direct mechanistic basis for ensuring the honesty of many secondary sexual signals, to the ‘Aerobic Activity Hypothesis, which predicts that it is the aerobic activity involved with signal production (i.e. vocal performance or defending a large territory) and not testosterone directly that links signal quality and oxidative stress. Males singing at faster rates had higher levels of both reactive oxygen metabolites and non‐enzymatic antioxidant capacity in the plasma (i.e. without an increase in overall oxidative stress), enabling certain males to produce high‐quality signals while also mitigating the costs of an associated increase in oxidative stress. However, these results were completely independent of plasma testosterone levels, supporting the role of aerobic performance in directly affecting oxidative stress. Although song performance was not linked to reproductive parameters in our data set, our research is the first to test these competing hypotheses in a behavioural trait and results suggest that oxidative stress may be an underlying physiological cost preventing low‐quality individuals from producing high‐quality signals.
Sequence and structure‐based prediction of fructosyltransferase activity for functional subclassification of fungal GH32 enzymes
Authors: Trollope Kim M. , van Wyk Niël , Kotjomela Momo A. , Volschenk Heinrich 
Published: October 2015

Sucrolytic enzymes catalyse sucrose hydrolysis or the synthesis of fructooligosaccharides (FOSs), a prebiotic in human and animal nutrition. FOS synthesis capacity differs between sucrolytic enzymes. Amino‐acid‐sequence‐based classification of FOS synthesizing enzymes would greatly facilitate the in silico identification of novel catalysts, as large amounts of sequence data lie untapped. The development of a bioinformatics tool to rapidly distinguish between high‐level FOSs synthesizing predominantly sucrose hydrolysing enzymes from fungal genomic data is presented. Sequence comparison of functionally characterized enzymes displaying low‐ and high‐level FOS synthesis revealed conserved motifs unique to each group. New light is shed on the sequence context of active site residues in three previously identified conserved motifs. We characterized two enzymes predicted to possess low‐ and high‐level FOS synthesis activities based on their conserved motif sequences. FOS data for the enzymes confirmed our successful prediction of their FOS synthesis capacity. Structural comparison of enzymes displaying low‐ and high‐level FOS synthesis identified steric hindrance between nystose and a long loop region present only in low‐level FOS synthesizers. This loop is proposed to limit the synthesis of FOS species with higher degrees of polymerization, a phenomenon observed among enzymes displaying low‐level FOS synthesis. Conserved sequence motifs surrounding catalytic residues and a distant structural determinant were identifiers of FOS synthesis capacity and allow for functional annotation of sucrolytic enzymes directly from amino acid sequence. The tool presented may also be useful to study the structure–function relationships of β‐fructofuranosidases by identifying mutations present in a group of closely related enzymes displaying similar function.