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The 9p21.3 genomic locus is a hot spot for disease-associated single-nucleotide polymorphisms (SNPs), and its strongest associations are with coronary artery disease (CAD). The disease-associated SNPs are located within the sequence of a long noncoding RNA ANRIL, which potentially contributes to atherogenesis by regulating vascular cell stress and proliferation, but also affects pancreatic β-cell proliferation. Altered expression of a neighboring gene, CDKN2B , has been also recognized to correlate with obesity and hepatic steatosis in people carrying the risk SNPs. In the present study, we investigated the impact of 9p21.3 on obesity accompanied by hyperlipidemia in mice carrying a deletion of the murine ortholog for the 9p21.3 (Chr4 Δ70/Δ70 ) risk locus in hyperlipidemic Ldlr -/- ApoB 100/100 background. The Chr4 Δ70/Δ70 mice showed decreased mRNA expression of insulin receptors in white adipose tissue already at a young age, which developed into insulin resistance and obesity by aging. In addition, the Sirt1-Ppargc1a-Ucp2 pathway was downregulated together with the expression of Cdkn2b, specifically in the white adipose tissue in Chr4 Δ70/Δ70 mice. These results suggest that the 9p21.3 locus, ANRIL lncRNA, and their murine orthologues may regulate the key energy metabolism pathways in a white adipose tissue-specific manner in the presence of hypercholesterolemia, thus contributing to the pathogenesis of metabolic syndrome.

The crisis resilience of vital social systems is currently the target of constant development efforts in Finland, as their drifting into crisis would weaken societies' functional abilities, safety, and security. This is also the case regarding the Finnish health care system. In an attempt to move beyond existing frameworks of crisis imagination, this article takes an unconventional stance by elucidating endogenous crisis dynamics present in the Finnish health care system. Delphi process was conducted for top experts in Finnish health care and crisis management. With a dissensus-seeking orientation, our aim was to fertilize disagreements among panelists to reveal key vulnerabilities in the health system. Despite our efforts to evoke dissensus, the panelists ended up generating a consensus that aims to protect the underlying assumptions of the health system's knowledge structure. Through inductive analysis of expert discourses, the data was analyzed through our research question "what constitutes a crisis-proof health system and a crisis-prone health system". What is framed as a strength of the system by our panelists, namely the ability to maintain legitimacy, improve efficiency, and guarantee continuity, can still have questionable implications that are left ungrasped. A system's theory approach illustrates how such effects can develop and escalate beyond the reach of social interventions, and thus be predisposed to cause objectionable yet concealed social crises. The discussion illustrates how these endogenous crisis dynamics could be seen to materialize in real-life cases., (© 2024. The Author(s).)

Spiny brown dinoflagellate cysts are commonly used as sea-ice indicators in the Arctic, but their biological affinities are not well known. We present the first indication of hitherto temperate Protoperidinium tricingulatum in the Arctic based on single-cell LSU rDNA sequencing from sediments of the Disko Bay-Vaigat Sound, West Greenland. The morphological similarity of the sequenced cyst morphotype to the sea-ice indicator Islandinium? cezare morphotype 1 is striking. The morphology of the isolated cysts, as well as those observed in the total cyst assemblage following standard palynological preparation, both resemble either I.? cezare morphotype 1 or P. tricingulatum, suggesting that the specimens may in fact be close morphological variants of the same species. In addition, nine LSU rDNA sequences were obtained from morphological variants assigned to Islandinium minutum s.l.: including both subspecies minutum and subspecies barbatum. The two subspecies could not be differentiated based on partial LSU rDNA sequencing. Overall, Arctic spiny brown dinoflagellate cyst species may be morphologically more diverse and taxonomically more complex than shown earlier and further genetic and morphological studies are needed. Importantly, the value of cysts as palaeoecological indicators depends on a sound understanding of their biological affinity and taxonomy., (© 2023 The Authors. Journal of Eukaryotic Microbiology published by Wiley Periodicals LLC on behalf of International Society of Protistologists.)

We critically re-examine 17 records of fossils currently assigned to the lepidopteran superfamily Bombycoidea, which includes the silk moths, emperor moths and hawk moths. These records include subfossils, compression and impression fossils, permineralizations and ichnofossils. We assess whether observable morphological features warrant their confident assignment to the superfamily. None of the examined fossils displays characters that allow unequivocal identification as Sphingidae, but three fossils and a subfossil ( Mioclanis shanwangiana Zhang, Sun and Zhang, 1994, two fossil larvae, and a proboscis in asphaltum) have combinations of diagnostic features that support placement in the family. The identification of a fossil pupa as Bunaeini (Saturniidae) is well supported. The other fossils that we evaluate lack definitive bombycoid and, in several cases, even lepidopteran characters. Some of these dubious fossils have been used as calibration points in earlier studies casting doubt on the resulting age estimates. All fossil specimens reliably assigned to Bombycoidea are relatively young, the earliest fossil evidence of the superfamily dating to the middle Miocene., Competing Interests: The authors declare that they have no competing interests., (© 2023 Heikkilä et al.)

The leaf-roller moth tribe Grapholitini comprises about 1200 described species and contains numerous notorious pests of fruits and seeds. The phylogeny of the tribe has been little studied using contemporary methods, and the monophyly of several genera remains questionable. In order to provide a more robust phylogenetic framework for the group, we conducted a multiple-gene phylogenetic analysis of 104 species representing 27 genera of Grapholitini and 29 outgroup species. Divergence time, ancestral area, and host plant usage were also inferred to explore evolutionary trends in the tribe. Our analyses indicate that Larisa and Corticivora, traditionally assigned to Grapholitini, are best excluded from the tribe. After removal of these two genera, the tribe is found to be monophyletic, represented by two major lineages-a Dichrorampha clade and a Cydia clade, the latter of which can be divided into seven generic groups. The genus Grapholita was found to be polyphyletic, comprising three different clades, and we propose three genera to accommodate these groups: Grapholita (sensu stricto), Aspila (formerly a subgenus of Grapholita) and Ephippiphora (formerly considered a synonym of Grapholita). We summarize each generic group, including related genera not included in our analysis, providing morphological, pheromone and food plant characters that support particular branches within the molecular hypotheses. Biogeographical analyses indicate that Grapholitini probably originated in the Nearctic, Afrotropical and Neotropical regions in the Lutetian of the middle Eocene (ca. 44.3 Ma). Our results also indicate that most groups in Grapholitini originated from Fabaceae-feeding monophagous or oligophagous ancestors, and that host plant shifts probably promoted species diversification within the tribe., (© 2023 The Authors. Cladistics published by John Wiley & Sons Ltd on behalf of Willi Hennig Society.)

Background: Cardiovascular diseases are the leading cause of death globally. In spite of the availability of improved treatments, there is still a large group of chronic ischemia patients who suffer from significant symptoms and disability. Thus, there is a clear need to develop new treatment strategies for these patients. Therapeutic angiogenesis is a novel therapy method which has shown promising results in preclinical studies. In this study, we evaluated safety and efficacy of adenoviral (Ad) VEGF-D ΔNΔC gene transfer for the treatment of myocardial ischemia in a pig model. Methods: Adenoviral VEGF-D ΔNΔC gene transfer was given to pigs ( n = 26) via intramyocardial injections using an electromechanical injection catheter. Angiogenic effects were evaluated in an acute myocardial infarction model ( n = 18) and functionality of the lymphatic vessels were tested in healthy porcine myocardium ( n = 8). AdLacZ was used as a control. Results: AdVEGF-D ΔNΔC induced safe and effective myocardial angiogenesis by inducing a four-fold increase in mean capillary area at the edge of the myocardial infarct six days after the gene transfer relative to the control AdLacZ group. The effect was sustained over 21 days after the gene transfer, and there were no signs of vessels regression. AdVEGF-D ΔNΔC also increased perfusion 3.4-fold near the infarct border zone relative to the control as measured by fluorescent microspheres. Ejection fraction was 8.7% higher in the AdVEGF-D ΔNΔC treated group 21 days after the gene transfer relative to the AdLacZ control group. Modified Miles assay detected a transient increase in plasma protein extravasation after the AdVEGF-D ΔNΔC treatment and a mild accumulation of pericardial effusate was observed at d6. However, AdVEGF-D ΔNΔC also induced the growth of functional lymphatic vasculature, and the amount of pericardial fluid and level of vascular permeability had returned to normal by d21. Conclusion: Endovascular intramyocardial AdVEGF-D ΔNΔC gene therapy proved to be safe and effective in the acute porcine myocardial infarction model and provides a new potential treatment option for patients with severe coronary heart disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pajula, Lähteenvuo, Lähteenvuo, Honkonen, Halonen, Hätinen, Kuivanen, Heikkilä, Nurro, Hartikainen and Ylä-Herttuala.)

By unpacking some of the dichotomies inherent in the concepts of vulnerability and disability, the article problematises some of the current legal approaches to disability in Finland. It argues that where used to single out population groups or individuals due to their embodied characteristics, the vulnerability paradigm can be seen to create binaries both among the persons with disabilities, and between the "vulnerable" persons with disabilities and the perception of a rational, self-standing and autonomous human being. To mitigate such binaries, the article explores an agency-centred discourse of vulnerability, one that recognises the co-existence of agency and vulnerability and sees agency as dynamic and responsive to the societal support structures that surround all of us. One of the central arguments of the article is that generalised approaches do, however, not suffice to make agency a reality for all persons with disabilities. Given the extensive diversity of intra-group variations between persons with disabilities, individualised solutions are needed for agency to be possible for all. To overcome objectification and de-agencification - and to enhance agency - this diversity of situations, needs and contexts of lived-in realities of individuals also needs to be expressly reflected in the legal language in addressing disability., (© The Author(s) 2022.)

Background: Nurses frequently face ethically demanding situations in their work, and these may lead to stress of conscience. Working life is currently accelerating and job demands are intensifying. These intensified job demands include (1) work intensification, (2) intensified job-related planning demands, (3) intensified career-related planning demands, and (4) intensified learning demands. At the same time, many healthcare organizations are implementing major organizational changes that have an influence on personnel., Aim: The aim of the study was to investigate the association between intensified job demands and stress of conscience, and whether their association is moderated by organizational change experiences among nurses. Experiences of organizational change may expose employees to stress of conscience or serve as a buffer because employees appraise, involve, and cope with changes differently., Research Design: Questionnaires measuring stress of conscience, intensified job demands, and organizational change experiences were completed by nurses (n = 511) in a healthcare district undergoing a major organizational change., Ethical Considerations: Throughout, the study procedures were implemented according to the guidelines of the Finnish National Board on Research Integrity and the 1964 Helsinki Declaration and its later amendments. According to the Finnish regulations, because participation was voluntary, informed consent was requested, and participants were advised of their right to withdraw from the study at will. No permission from an ethics committee was necessary., Findings: Work intensification and personal worry considering organizational change were associated with more severe stress of conscience among nurses. Nurses' experiences of managements' competent handling of organizational change buffered the association between work intensification and stress of conscience., Conclusions: During organizational changes, management may alleviate nurses' stress of conscience by proper communication and support procedures.

Background: Early childhood education and care (ECEC) centers are ideal venues for food education. As smartphones and tablets are becoming increasingly popular in ECEC centers, technology can be used to deliver such pedagogical content. Evidence suggests that video games can affect fruit and vegetable (FV) consumption among 9- to 12-year-old children, but studies among preschoolers are scarce., Objective: This paper describes the development of the Mole's Veggie Adventures app and its effectiveness in increasing FV acceptance among Finnish and Polish preschoolers aged 3 to 6 years., Methods: A multiprofessional team created an app to be used in ECEC centers in groups of 3 to 10 children. The app aimed to increase vegetable acceptance, and it was built using elements that support the development of self-regulation and social skills. Altogether, 7 Finnish and 4 Polish ECEC centers participated in the study. Before randomization, parents reported background factors and their children's willingness to taste different FVs. The ECEC professionals in the intervention arm were instructed to use the app at least once a week during the 3- to 4-week intervention period. The main outcomes in this unblinded, cluster-randomized study were FV acceptance and relative FV acceptance. The first was calculated as a sum variable describing the children's willingness to taste 25 different FVs, the second as FV acceptance divided by the number of FVs served. We used analysis of covariance to compare the FV acceptance and relative FV acceptance scores between the intervention and control groups at follow-up., Results: A total of 221 children were included in the analysis. At follow-up, the intervention group (115/221, 52%) had higher FV acceptance scores (baseline adjusted difference of mean 7.22; 95% CI 1.41-13.03) than the control group (106/221, 48%). The intervention effect was parallel for relative FV acceptance scores (baseline adjusted difference of mean 0.28; 95% CI 0.05-0.52)., Conclusions: The Mole's Veggie Adventures app has the potential to increase FV acceptance among preschoolers and can be a valuable tool in supporting food education in ECEC centers. Furthermore, the app can be feasibly incorporated into preschool routines in countries with different educational environments., Trial Registration: ClinicalTrials.gov NCT05173311; https://tinyurl.com/4vfbh283., (©Henna Vepsäläinen, Essi Skaffari, Katarzyna Wojtkowska, Julia Barlińska, Satu Kinnunen, Riikka Makkonen, Maria Heikkilä, Mikko Lehtovirta, Carola Ray, Eira Suhonen, Jaakko Nevalainen, Nina Sajaniemi, Maijaliisa Erkkola. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 04.01.2022.)

We studied the evolutionary relationship of two widely distributed parapatric butterfly species, Melitaea athalia and Melitaea celadussa , using the ddRAD sequencing approach, as well as genital morphology and mtDNA data. M. athalia was retrieved as paraphyletic with respect to M. celadussa . Several cases of mito-nuclear discordance and morpho-genetic mismatch were found in the contact zone. A strongly diverged and marginally sympatric clade of M. athalia from the Balkans was revealed. An in-depth analysis of genomic structure detected high levels of admixture between M. athalia and M. celadussa at the contact zone, though not reaching the Balkan clade. The demographic modelling of populations supported the intermediate genetic make-up of European M. athalia populations with regards to M. celadussa and the Balkan clade. However, the dissimilarity matrix of genotype data (PCoA) suggested the Balkan lineage having a genetic component that is unrelated to the athalia - celadussa group. Although narrowly sympatric, almost no signs of gene flow were found between the main M. athalia group and the Balkan clade. We propose two possible scenarios on the historical evolution of our model taxa and the role of the last glacial maximum in shaping their current distribution. Finally, we discuss the complexities regarding the taxonomic delimitation of parapatric taxa.

The COVID-19 emergency has urged companies to operate in new ways to face supply chain interruptions, shifts in customer demand, and risks to workforce health. The organizational ability to respond to critical contingencies is crucial for business leaders in the perspective of continuing business. In our research, we investigate the actions undertaken by 50 world-leading corporations to respond to the pandemic. Applying content analysis to web pages and social network posts, we extract 77 actions related to 13 sub-areas and integrate these into a five-level framework that encompasses operations, customer, workforce, leadership, and community-related responses. We also describe six illustrative company examples of how the emergency can generate opportunities for creating new value. The study advances the scholarly discussion on the impact of emergencies on business continuity and can help leaders define response strategies and actions in the current challenge., (© 2021 Kelley School of Business, Indiana University. Published by Elsevier Inc.)

The aim of this study was to provide information on energy availability (EA), macronutrient intake, nutritional periodization practices, and nutrition knowledge in young female cross-country skiers. A total of 19 skiers filled in weighted food and training logs before and during a training camp. Nutrition knowledge was assessed via a validated questionnaire. EA was optimal in 11% of athletes at home (mean 33.7 ± 9.6 kcal·kgFFM -1 ·d -1 ) and in 42% at camp (mean 40.3 ± 17.3 kcal·kgFFM -1 ·d -1 ). Most athletes (74%) failed to meet recommendations for carbohydrate intake at home (mean 5.0 ± 1.2 g·kg -1 ·d -1 ) and 63% failed to do so at camp (mean 7.1 ± 1.6 g·kg -1 ·d -1 ). The lower threshold of the pre-exercise carbohydrate recommendations was met by 58% and 89% of athletes while percentages were 26% and 89% within 1 h after exercise, at home and at camp, respectively. None of the athletes met the recommendations within 4 h after exercise. Nutrition knowledge was associated with EA at home (r = 0.52, p = 0.023), and with daily carbohydrate intake at home (r = 0.62, p = 0.005) and at camp (r = 0.52, p = 0.023). Carbohydrate intake within 1 and 4 h post-exercise at home was associated with better nutrition knowledge (r = 0.65, p = 0.003; r = 0.53, p = 0.019, respectively). In conclusion, young female cross-county skiers had difficulties meeting recommendations for optimal EA and carbohydrate intake. Better nutrition knowledge may help young athletes to meet these recommendations.

Nanoscale SnO 2 has many important properties ranging from sorption of metal ions to gas sensing. Using a novel electroblowing method followed by calcination, we synthesized SnO 2 and composite SnO 2 /SiO 2 submicron fibers with a Sn : Si molar ratio of 3 : 1. Different calcination temperatures and heating rates produced fibers with varying structures and morphologies. In all the fibers SnO 2 was detected by XRD indicating the SnO 2 /SiO 2 fibers to be composite instead of complete mixtures. We studied the Co 2+ separation ability of the fibers, since 60 Co is a problematic contaminant in nuclear power plant wastewaters. Both SnO 2 and SnO 2 /SiO 2 fibers had an excellent Co 2+ uptake with their highest uptake/ K d values being 99.82%/281 000 mL g -1 and 99.79%/234 000 mL g -1 , respectively. Compared to the bare SnO 2 fibers, the SiO 2 component improved the elasticity and mechanical strength of the composite fibers which is advantageous in dynamic column operation., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

This article stresses the importance of understanding that women and men in gender-segregated programmes experience their gender minority positions very differently. It stems from an interest in the kind of interventions that academia should address in order to reduce gender segregation and provide women and men with the same educational opportunities and personal development. In relation to the obvious and continuing gender differences along a horizontal dimension, previous research seems to have had a limited impact in breaking gender stereotypes and promoting women and men to more atypical fields. The empirical data consists of 25 semi-structured, individual interviews from underrepresented students' gender-related experiences/thoughts about their programmes. By using the concepts of "visibility," "sense of belonging," and "negotiating otherness" to analyze how negotiation and belonging are part of students' everyday university lives this study's most important contributions are its findings regarding the differentiations in visibility. A continuum of visibility experiences is explored, from men who receive positive attention to women who are being considered as less knowledgeable. Our visibility scale indicates, as does previous research, that there are differences between how female and male students become visible, but the differences can also appear within both groups of students. This knowledge is crucial when designing interventions so as to provide positive study environments for both women and men. Also-in a broader perspective-it is important in order to recruit and ensure that gender minority students remain in the programs., (Copyright © 2020 Heikkilä, Isaksson and Stranne.)

Hypoxia-inducible factor (HIF), an αβ dimer, is the master regulator of oxygen homeostasis with hundreds of hypoxia-inducible target genes. Three HIF isoforms differing in the oxygen-sensitive α subunit exist in vertebrates. While HIF-1 and HIF-2 are known transcription activators, HIF-3 has been considered a negative regulator of the hypoxia response pathway. However, the human HIF3A mRNA is subject to complex alternative splicing. It was recently shown that the long HIF-3α variants can form αβ dimers that possess transactivation capacity. Here, we show that overexpression of the long HIF-3α2 variant induces the expression of a subset of genes, including the erythropoietin (EPO) gene, while simultaneous downregulation of all HIF-3α variants by siRNA targeting a shared HIF3A region leads to downregulation of EPO and additional genes. EPO mRNA and protein levels correlated with HIF3A silencing and HIF-3α2 overexpression. Chromatin immunoprecipitation analyses showed that HIF-3α2 binding associated with canonical hypoxia response elements in the promoter regions of EPO. Luciferase reporter assays showed that the identified HIF-3α2 chromatin-binding regions were sufficient to promote transcription by all three HIF-α isoforms. Based on these data, HIF-3α2 is a transcription activator that directly regulates EPO expression.

Hypoxia inactivates hypoxia-inducible factor (HIF) prolyl 4-hydroxylases (HIF-P4Hs), which stabilize HIF and upregulate genes to restore tissue oxygenation. HIF-P4Hs can also be inhibited by small molecules studied in clinical trials for renal anemia. Knowledge of systemic long-term inactivation of HIF-P4Hs is limited but crucial, since HIF overexpression is associated with cancers. We aimed to determine the effects of systemic genetic inhibition of the most abundant isoenzyme HIF prolyl 4-hydroxylase-2 (HIF-P4H-2)/PHD2/EglN1 on life span and tissue homeostasis in aged mice. Our data showed no difference between wild-type and HIF-P4H-2-deficient mice in the average age reached. There were several differences, however, in the primary causes of death and comorbidities, the HIF-P4H-2-deficient mice having less inflammation, liver diseases, including cancer, and myocardial infarctions, and not developing anemia. No increased cancer incidence was observed due to HIF-P4H-2-deficiency. These data suggest that chronic inactivation of HIF-P4H-2 is not harmful but rather improves the quality of life in senescence., (© 2020 Federation of American Societies for Experimental Biology.)

We critically re-examine nine of the ten fossil specimens currently assigned to Hepialidae. Three fossils with impressions of wing veins and scales placed in the fossil genus Prohepialus Piton, 1940, and two mummified larvae that show apomorphic characters, have features that support placement in Hepialidae. The other four fossils that we evaluate, Prohepialus incertus Piton, 1940; Oiophassus nycterus Zhang, 1989; Protohepialus comstocki Pierce, 1945; and a fossil scale, lack definitive hepialid characters. One of these, Prohepialus incertus Piton, 1940, appears to represent a symphytan (Hymenoptera), and is excluded from Lepidoptera. The fossilized wings placed in Prohepialus by Jarzembowski display numerous features that indicate a proximate phylogenetic relationship to extant members of the hepialid genus Sthenopis Packard and related genera., Competing Interests: The authors declare there are no competing interests., (©2019 Simonsen et al.)

Both stable and radioactive antimony are common industrial pollutants. For antimonate (Sb(v)) removal from industrial waste water, we synthesized submicron zirconium dioxide (ZrO 2 ) fibers by electroblowing and calcination of the as-electroblown fibers. The fibers are amorphous after calcination at 300 and 400 °C and their average diameter is 720 nm. The fibers calcined at 500 to 800 °C have an average diameter of 570 nm and their crystal structure transforms from tetragonal to monoclinic at the highest calcination temperatures. We investigated Sb(v) adsorption capacity of the synthesized ZrO 2 fibers as a function of pH, adsorption isotherm at pH 6 and adsorption kinetics at pH 7. The tetragonal ZrO 2 fibers calcined at 500 °C exhibited the best potential for Sb(v) remediation with Sb(v) uptake of 10 mg g -1 at pH 2 and a maximum Sb(v) uptake of 8.6 mg g -1 in the adsorption isotherm experiment. They also reached 30% of 7 days' Sb(v) uptake in only a minute. The adsorption kinetics followed the Elovich model., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Athletes often have significant gaps in their nutrition knowledge. Thus, the aim of this study was to investigate whether young Finnish endurance athletes' nutrition knowledge and dietary intake can be improved through an education intervention with or without a mobile food application. Seventy-nine endurance athletes, 18.0 years (SD: 1.4), participated in this randomized, controlled intervention. We compared the effects of participatory nutrition education sessions alone (group EDU) to those including the use of a mobile food application (group EDU + APP) for four days after each session. Both groups attended three 90-min education sessions fortnightly. The participants completed a validated nutrition knowledge questionnaire in Weeks 0, 5, and 17, and a three-day food diary in Weeks 0 and 17. The education plan was based on the Self-Determination Theory and the concept of meaningful learning process. The EDU group's nutrition knowledge scores were: 78 (week 0), 85 (week 5), and 84 (week 17) and the EDU + APP group's 78, 86, and 85, respectively. Nutrition knowledge increased significantly (main effect of time ( p < 0.001)), but we observed no significant group × time interaction ( p = 0.309). The changes in dietary intakes were minor ( p > 0.05). The amount of carbohydrates was below endurance athletes' recommendations throughout the intervention. The reported energy intakes were also below the estimated energy expenditures. In conclusion, nutrition knowledge improved significantly after only three education sessions and food diary feedback, but the mobile app did not improve learning further. However, the nutrition education intervention alone was not enough to change dietary intake.

The need for robust estimates of times of divergence is essential for downstream analyses, yet assessing this robustness is still rare. We generated a time-calibrated genus-level phylogeny of butterflies (Papilionoidea), including 994 taxa, up to 10 gene fragments and an unprecedented set of 12 fossils and 10 host-plant node calibration points. We compared marginal priors and posterior distributions to assess the relative importance of the former on the latter. This approach revealed a strong influence of the set of priors on the root age but for most calibrated nodes posterior distributions shifted from the marginal prior, indicating significant information in the molecular data set. Using a very conservative approach we estimated an origin of butterflies at 107.6 Ma, approximately equivalent to the latest Early Cretaceous, with a credibility interval ranging from 89.5 Ma (mid Late Cretaceous) to 129.5 Ma (mid Early Cretaceous). In addition, we tested the effects of changing fossil calibration priors, tree prior, different sets of calibrations and different sampling fractions but our estimate remained robust to these alternative assumptions. With 994 genera, this tree provides a comprehensive source of secondary calibrations for studies on butterflies., (© The Author(s) 2019. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In the context of monitoring dogs, usually, accelerometers have been used to measure the dog's movement activity. Here, we study another application of the accelerometers (and gyroscopes)-seismocardiography (SCG) and gyrocardiography (GCG)-to monitor the dog's heart. Together, 3-axis SCG and 3-axis GCG constitute of 6-axis mechanocardiography (MCG), which is inbuilt to most modern smartphones. Thus, the objective of this study is to assess the feasibility of using a smartphone-only solution to studying dog's heart., Methods: A clinical trial (CT) was conducted at the University Small Animal Hospital, University of Helsinki, Finland. 14 dogs (3 breeds) including 18 measurements (about one half of all) where the dog's status was such that it was still and not panting were further selected for the heart rate (HR) analysis (each signal with a duration of 1 min). The measurement device in the CT was a custom Holter monitor including synchronized 6-axis MCG and ECG. In addition, 16 dogs (9 breeds, one mixed-breed) were measured at home settings by the dog owners themselves using Sony Xperia Android smartphone sensor to further validate the applicability of the method., Results: The developed algorithm was able to select 10 good-quality signals from the 18 CT measurements, and for 7 of these, the automated algorithm was able to detect HR with deviation below or equal to 5 bpm (compared to ECG). Further visual analysis verified that, for approximately half of the dogs, the signal quality at home environment was sufficient for HR extraction at least in some signal locations, while the motion artifacts due to dog's movements are the main challenges of the method., Conclusion: With improved data analysis techniques for managing noisy measurements, the proposed approach could be useful in home use. The advantage of the method is that it can operate as a stand-alone application without requiring any extra equipment (such as smart collar or ECG patch).

Coptoformica Müller, 1923 is a subgenus of Formica Linnaeus, 1758 that consists of c. a dozen species of ants that typically inhabit open grassy habitats and build small nest mounds. The most recent addition to the group is Formica fennica Seifert, 2000. The description was based on morphological characters, but the species status has not been confirmed by molecular methods. In this study, we use thirteen DNA microsatellite markers and a partial mitochondrial COI gene sequence to assess the species status of F. fennica , by comparing the genetic variation among samples identified as F. fennica and six other boreal Formica (Coptoformica) species. Most of the species studied form separate, discontinuous clusters in phylogenetic and spatial analyses with only little intraspecific genetic variation. However, both nuclear and mitochondrial markers fail to separate the species pair F. exsecta Nylander, 1846 and F. fennica despite established morphological differences. The genetic variation within the F. exsecta/fennica group is extensive, but reflects spatial rather than morphological differences. Finnish F. fennica populations studied so far should not be considered a separate species, but merely a morph of F. exsecta ., Competing Interests: The authors declare there are no competing interests.

Background: Previous studies illustrated that chronic rhinosinusitis and allergic rhinitis represent individual and socioeconomic burdens to a patient. However, few studies exist on the health-related quality of life (HRQoL) amongst other rhinologic patients. Our study investigated the generic HRQoL in different rhinologic diseases., Methodology: Unselected adult rhinologic patients requiring special care at the Helsinki University Hospital were enrolled in this cross-sectional, questionnaire-based prospective study in February, May, August and November 2014. Patients were mailed a medical history questionnaire and a generic 15-dimension (15D) HRQoL questionnaire. Diagnostic data were collected from electronic patient records following outpatient visits. Patient HRQoL scores were compared to an age- and sex-standardised general population sample obtained from a large national health examination survey., Results: This study consisted of 337 rhinologic patients (mean age 50.2 years, 50.4% men). The mean 15D score amongst rhinologic patients (0.865) was both statistically significant and clinically poorer than that amongst the general population (0.929). Rhinologic patients fared poorly on most dimensions of the 15D instrument, particularly on sleep, discomfort and symptoms, breathing and vitality. Patients with obstructive sleep apnoea (OSA) were particularly affected. Yet, comparing the five most common rhinologic diagnostic groups revealed no significant differences in the mean 15D scores., Conclusions: Rhinologic diseases, independent of the underlying cause, substantially and negatively affect patients' HRQoL. OSA decreases HRQoL in these patients, although patients without an OSA diagnosis still suffer from a clinically important impairment of HRQoL and poor quality sleep., (© 2018 John Wiley & Sons Ltd.)

The identifications of known fossils currently placed in the lepidopteran superfamily Pyraloidea are critically re-examined. Of the eleven fossils examined, only three are confirmed to show morphological characters supporting placement in the superfamily. These fossils include a crambid larva in Baltic Amber, Baltianania yantarnia, Solis gen. n. et sp. n. and the oldest known fossil pyraloid, Eopyralis morsae Simonsen, gen. n. et sp. n. The third fossil, Glendotricha olgae Kusnezov, 1941, displays apomorphic characters for Pyraloidea, but is shown to be an inclusion in copal, not Baltic amber as had been reported. Seven fossil specimens lack reliable characters and cannot be assigned to Pyraloidea with certainty: Pyralites obscurus Heer, 1856; Pyralites preecei Jarzembowski, 1980; Petisca dryellina Martins-Neto, 1998; three fossil larvae tentatively identified as Pyralidae by Zeuner (1931); and Gallerites keleri Kernbach, 1967. A possible fossil pyraloid in Mizunami amber could not be located in museum collections and available literature does not provide details to assess the validity of the identification. We discuss the contribution of the reliably identified fossils towards better understanding the evolutionary history of Pyraloidea.

The nutrition knowledge of athletes and coaches is often inadequate. However, athletes need sufficient knowledge of this subject to understand the importance of food choices for their athletic performance, recovery, and overall health. Adequate nutrition knowledge and skills are important for coaches because they are often the most significant source of nutrition knowledge for their athletes. Most previous nutrition knowledge studies have been carried out in team sports and outside Scandinavia. The aim of this study, therefore, was to evaluate the nutrition knowledge of Finnish endurance athletes (156 males and 156 females; age = 17.9 ± 1.2 years) and their coaches (69 males and 25 females; age = 44.3 ± 12.3 years). The three main sports among the participants were cross-country skiing (n = 53 coaches and n = 111 athletes), orienteering (n = 13 and n = 110), and biathlon (n = 6 and n = 38). On average, the coaches (N = 94) answered 81% ± 9% of the 79 nutrition questionnaire items correctly, whereas the respective result was 73% ± 9% among the athletes (N = 312). The coaches had significantly (p < .001) better nutrition knowledge of all the five subcategories of the questionnaire, whereas the "dietary supplements" and "nutrition recommendations for endurance athletes" subcategories appeared particularly difficult for the athletes. The average nutrition knowledge score of athletes was relatively low. As nutrition knowledge may have a positive association with athletes' food choices and subsequent dietary intake, Finnish endurance athletes and coaches would benefit from enhanced nutrition education.

The Younger Dryas (YD) cold reversal interrupts the warming climate of the deglaciation with global climatic impacts. The sudden cooling is typically linked to an abrupt slowdown of the Atlantic Meridional Overturning Circulation (AMOC) in response to meltwater discharges from ice sheets. However, inconsistencies regarding the YD-response of European summer temperatures have cast doubt whether the concept provides a sufficient explanation. Here we present results from a high-resolution global climate simulation together with a new July temperature compilation based on plant indicator species and show that European summers remain warm during the YD. Our climate simulation provides robust physical evidence that atmospheric blocking of cold westerly winds over Fennoscandia is a key mechanism counteracting the cooling impact of an AMOC-slowdown during summer. Despite the persistence of short warm summers, the YD is dominated by a shift to a continental climate with extreme winter to spring cooling and short growing seasons.

We re-evaluate eleven fossils that have previously been assigned to the family Tortricidae, describe one additional fossil, and assess whether observable morphological features warrant confident assignment of these specimens to this family. We provide an overview of the age and origin of the fossils and comment on their contribution towards understanding the phylogeny of the Lepidoptera. Our results show that only one specimen, Antiquatortia histuroides Brown Baixeras gen. and sp. nov., shows a character considered synapomorphic for the family. Six other fossils (Electresia zalesskii Kusnezov, 1941; Tortricidrosis inclusa Skalski, 1973; Tortricites skalskii Kozlov, 1988; Tortricibaltia diakonoffi Skalski, 1992; Polyvena horatis Poinar and Brown, 1993 and a trace fossil purported to be larval feeding damage of Retinia resinella (Linnaeus, 1758)) exhibit a combination of homoplastic characters typical of tortricid moths or characteristic feeding damage. An unnamed species doubtfully assigned to Olethreutinae by Skalski (1992), Spatalistiforma submerga Skalski, 1992, Tortricites florissantanus (Cockerell, 1907), Tortricites destructus (Cockerell, 1916) and Tortricites sadilenkoi Kozlov, 1988 do not show enough character evidence to be convincingly placed in Tortricidae. Therefore, we transfer the three latter species from the collective group Tortricites Kozlov, 1988, defined as an assemblage of fossil leafrollers that cannot be placed with certainty in known genera, to Paleolepidopterites Kozlov, new collective group, defined as a group of fossil lepidopterans whose assignment to a certain family is currently impossible.

In order to establish a baseline for proxy-based reconstructions for the Young Sound-Tyrolerfjord system (Northeast Greenland), we analysed the spatial distribution of primary production and sea ice proxies in surface sediments from the fjord, against monitoring data from the Greenland Ecosystem Monitoring Programme. Clear spatial gradients in organic carbon and biogenic silica contents reflected marine influence, nutrient availability and river-induced turbidity, in good agreement with in situ measurements. The sea ice proxy IP 25 was detected at all sites but at low concentrations, indicating that IP 25 records from fjords need to be carefully considered and not directly compared to marine settings. The sea ice-associated biomarker HBI III revealed an open-water signature, with highest concentrations near the mid-July ice edge. This proxy evaluation is an important step towards reliable palaeoenvironmental reconstructions that will, ultimately, contribute to better predictions for this High Arctic ecosystem in a warming climate.

We show here that mice hypomorphic for hypoxia-inducible factor prolyl 4-hydroxylase-2 (HIF-P4H-2) (Hif-p4h-2 (gt/gt)), the main regulator of the stability of the HIFα subunits, have normoxic stabilization of HIF-1α and HIF-2α in their skeletal muscles. The size of the capillaries, but not their number, was increased in the skeletal muscles of the Hif-p4h-2 (gt/gt) mice, whereas the amount of glycogen was reduced. The expression levels of genes for glycolytic enzymes, glycogen branching enzyme 1 and monocarboxylate transporter 4, were increased in the Hif-p4h-2 (gt/gt) skeletal muscles, whereas no significant increases were detected in the levels of any vasculature-influencing factor studied. Serum lactate levels of the Hif-p4h-2 (gt/gt) mice recovered faster than those of the wild type following exercise. The Hif-p4h-2 (gt/gt) mice had elevated hepatic phosphoenolpyruvate carboxykinase activity, which may have contributed to the faster clearance of lactate. The Hif-p4h-2 (gt/gt) mice had smaller infarct size following limb ischemia-reperfusion injury. The increased capillary size correlated with the reduced infarct size. Following ischemia-reperfusion, glycogen content and ATP/ADP and CrP/Cr levels of the skeletal muscle of the Hif-p4h-2 (gt/gt) mice were higher than in the wild type. The higher glycogen content correlated with increased expression of phosphofructokinase messenger RNA (mRNA) and the increased ATP/ADP and CrP/Cr levels with reduced apoptosis, suggesting that HIF-P4H-2 deficiency supported energy metabolism during ischemia-reperfusion and protection against injury. Key messages: HIF-P4H-2 deficiency protects skeletal muscle from ischemia-reperfusion injury. The mechanisms involved are mediated via normoxic HIF-1α and HIF-2α stabilization. HIF-P4H-2 deficiency increases capillary size but not number. HIF-P4H-2 deficiency maintains energy metabolism during ischemia-reperfusion.

Background: Ditrysia comprise close to 99 % of all butterflies and moths. The evolutionary relationships among the ditrysian superfamilies have received considerable attention in phylogenetic studies based on DNA and transcriptomic data, but the deepest divergences remain for large parts unresolved or contradictory. To obtain complementary insight into the evolutionary history of the clade, and to test previous hypotheses on the subdivision of Ditrysia based on morphology, we examine the morphology of larvae, pupae and adult males and females of 318 taxa representing nearly all ditrysian superfamilies and families. We present the most comprehensive morphological dataset on Ditrysia to date, consisting of over 500 morphological characters. The data are analyzed alone and combined with sequence data (one mitochondrial and seven nuclear protein-coding gene regions, sequenced from 422 taxa). The full dataset consists of 473 exemplar species. Analyses are performed using maximum likelihood methods, and parsimony methods for the morphological dataset. We explore whether combining morphological data and DNA-data can stabilize taxa that are unstable in phylogenetic studies based on genetic data only., Results: Morphological characters are found phylogenetically informative in resolving apical nodes (superfamilies and families), but characters serving as evidence of relatedness of larger assemblages are few. Results include the recovery of a monophyletic Tineoidea, Sesioidea and Cossoidea, and a stable position for some unstable taxa (e.g. Epipyropidae, Cyclotornidae, Urodoidea + Schreckensteinioidea). Several such taxa, however, remain unstable even though morphological characters indicate a position in the tree (e.g. Immidae). Evidence supporting affinities between clades are suggested, e.g. a novel larval synapomorphy for Tineidae. We also propose the synonymy of Tineodidae with Alucitidae, syn. nov., Conclusions: The large morphological dataset provides information on the diversity and distribution of morphological traits in Ditrysia, and can be used in future research on the evolution of these traits, in identification keys and in identification of fossil Lepidoptera. The "backbone" of the phylogeny for Ditrysia remains largely unresolved. As previously proposed as an explanation for the scarcity of molecular signal in resolving the deeper nodes, this may be due to the rapid radiation of Ditrysia in the Cretaceous.

Gelechioidea are one of the most species rich and least studied superfamilies of Lepidoptera. We examine the interrelationships within the superfamily using the densest taxon sampling to date, combined with the most extensive ever morphological and molecular character data. We perform partitioned and combined analyses using maximum likelihood, Bayesian and parsimony approaches. The combined dataset consists of 155 exemplar species of Gelechioidea, representing nearly all subfamilies recognized in recent classifications. Parsimony analyses are performed with a dataset including 28 additional terminal taxa with only morphological data available. We use eight genes with a total of 6127 bp, and morphological data with 253 characters derived from larval, pupal, and adult morphology. The analyses of combined data yield more resolved trees and significantly better-supported groupings than either dataset when analysed alone. The recurrent monophyletic groupings in all our model-based analyses support a revision of the family classification. Deeper relationships vary between analyses and data partitions, leaving them ambiguous. The place of the root remains a challenge for future research. We propose a revised classification and suggest the division of Gelechioidea into 16 families. We redefine Depressariidae Meyrick, 1883 for a monophylum that includes Acriinae, Aeolanthinae, Cryptolechiinae, Depressariinae, Ethmiinae, Hypercalliinae, Hypertrophinae, Peleopodinae, Oditinae, Stenomatinae, Carcina, and a diversity of predominantly New World taxa previously excluded from Lypusidae (Amphisbatidae s. authors) but left without family position. A monophyletic Oecophoridae s. s., including Deuterogoniinae and Pleurotinae, is obtained for the first time with significant support. Elachistidae s. l. is found to be polyphyletic, and Elachistidae is restricted to comprise Agonoxeninae, Elachistinae, and Parametriotinae. Batrachedridae are polyphyletic, with several genera pending further study. Apart from the core Batrachedra, the taxa previously included in this family are grouped in an expanded Pterolonchidae, together with Coelopoetinae and Syringopainae. Lypusidae s. s. and Chimabachidae form a monophylum; Chimabachinae is united with Lypusidae as a subfamily, stat. n. Our results contradict the subfamily classifications of several families, notably Lecithoceridae and Autostichidae, but due to insufficient sampling of taxa we refrain from comprehensive taxonomic conclusions on the subfamily level, and encourage focused studies to resolve these groups., (© The Willi Hennig Society 2013.)

Calcium carbonate (CaCO3) fibers were prepared by electrospinning followed by annealing. Solutions consisting of calcium nitrate tetrahydrate (Ca(NO3)2·4H2O) and polyvinylpyrrolidone (PVP) dissolved in ethanol or 2-methoxyethanol were used for the fiber preparation. By varying the precursor concentrations in the electrospinning solutions CaCO3 fibers with average diameters from 140 to 290 nm were obtained. After calcination the fibers were identified as calcite by X-ray diffraction (XRD). The calcination process was studied in detail with high temperature X-ray diffraction (HTXRD) and thermogravimetric analysis (TGA). The initially weak fiber-to-substrate adhesion was improved by adding a strengthening CaCO3 layer by spin or dip coating Ca(NO3)2/PVP precursor solution on the CaCO3 fibers followed by annealing of the gel formed inside the fiber layer. The CaCO3 fibers were converted to nanocrystalline hydroxyapatite (HA) fibers by treatment in a dilute phosphate solution. The resulting hydroxyapatite had a plate-like crystal structure with resemblance to bone mineral. The calcium carbonate and hydroxyapatite fibers are interesting materials for bone scaffolds and bioactive coatings., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nanocrystalline hydroxyapatite thin films were fabricated on silicon and titanium by atomic layer deposition (ALD) of CaCO3 and its subsequent conversion to hydroxyapatite by diammonium hydrogen phosphate (DAP) solution. The effects of conversion process parameters to crystallinity and morphology of the films were examined. DAP concentration was found to be critical in controlling the crystal size and homogeneity of the films. The hydroxyapatite phase was identified by XRD. ToF-elastic recoil detection analysis studies revealed that the films are calcium deficient in relation to hydroxyapatite with a Ca/P ratio of 1.39 for films converted with 0.2 M DAP at 95 °C. The coatings prepared on titanium conformally follow the rough surface topography of the substrate, verifying that the good step coverage of the ALD method was maintained in the conversion process. The dissolution tests revealed that the coating was nondissolvable in the cell culture medium. Annealing the coated sample at 700 °C for 1 h seemed to enhance its bonding properties to the substrate. Also, the biocompatibility of the coatings was confirmed by human bone marrow derived cells in vitro. The developed method provides a new possibility to produce thin film coatings on titanium implants with bone-type hydroxyapatite that is biocompatible with human osteoblasts and osteoclasts.

One main limiting factor for the technoeconomics of future bioprocesses that use ionic liquids (ILs) is the recovery of the expensive and potentially toxic IL. We have demonstrated a new series of phase-separable ionic liquids, based on the hydrophobic tetraalkylphosphonium cation ([PRRRR](+)), that can dissolve lignin in the neat state but also hemicellulose and high-purity cellulose in the form of their electrolyte solutions with dipolar aprotic solvents. For example, the IL trioctylmethylphosphonium acetate ([P8881][OAc]) was demonstrated to dissolve up to 19 wt % of microcrystalline cellulose (MCC) at 60 °C with the addition of 40 wt % of DMSO. It was found that the MCC saturation point is dependent on the molar ratio of DMSO and IL in solution. At the optimum saturation, a ∼1:1 molar ratio of [P8881][OAc] to anhydroglucose units is observed, which demonstrates highly efficient solvation. This is attributed to the positive contribution that these more amphiphilic cation-anion pairs provide, in the context of the Lindman hypothesis. This effective dissolution is further illustrated by solution-state HSQC NMR spectroscopy on MCC. Finally, it is also demonstrated that these electrolytes are phase separable by the addition of aqueous solutions. The addition of 10 % NaOAc solution allows a near quantitative recovery of high-purity [P8881][OAc]. However, increased volumes of aqueous solution reduced the recovery. The regenerated material was found to partially convert into the cellulose II crystalline polymorph., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We examine the systematic position of the lepidopteran family Prodidactidae Epstein and Brown, 2003, which includes the single species Prodidactis mystica (Meyrick). We provide details on a morphological trait of the adult male hindcoxa that appears to link Prodidactidae with Hyblaeidae. This putative relationship is consistent with molecular data derived from five genes. Based on morphological and molecular evidence, we place Prodidactidae in Hyblaeoidea. Moreover, the apex of the larval spinneret is similarly modified in these families and in Thyrididae. This modification is unknown in other Lepidoptera and may prove to be a synapomorphy linking Thyridoidea and Hyblaeoidea. As the latter is not fully congruent with published molecular studies, we refrain from suggesting sister group position for Thyridoidea and Hyblaeoidea.

An endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to hydroxylate the α subunit of the hypoxia-inducible factor (HIF) in vitro and in cultured cells, but nothing is known about its roles in mammalian erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor, FG-4497, to P4h-tm(-/-) mice. This caused larger increases in serum Epo concentration and kidney but not liver Hif-1α and Hif-2α protein and Epo mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower in the P4h-tm(-/-) mice than in the wild-type. Similar, but not identical, differences were also seen between FG-4497-treated Hif-p4h-2 hypomorphic (Hif-p4h-2(gt/gt)) and Hif-p4h-3(-/-) mice versus wild-type mice. FG-4497 administration increased hemoglobin and hematocrit values similarly in the P4h-tm(-/-) and wild-type mice, but caused higher increases in both values in the Hif-p4h-2(gt/gt) mice and in hematocrit value in the Hif-p4h-3(-/-) mice than in the wild-type. Hif-p4h-2(gt/gt)/P4h-tm(-/-) double gene-modified mice nevertheless had increased hemoglobin and hematocrit values without any FG-4497 administration, although no such abnormalities were seen in the Hif-p4h-2(gt/gt) or P4h-tm(-/-) mice. Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis.

We review morphological characters considered important for understanding butterfly phylogeny and evolution in the light of recent large-scale molecular phylogenies of the group. A number of the most important morphological works from the past half century are reviewed and morphological character evolution is reassessed based on the most recent phylogenetic results. In particular, higher level butterfly morphology is evaluated based on a very recent study combining an elaborate morphological dataset with a similar molecular one. Special attention is also given to the families Papilionidae, Nymphalidae and Hesperiidae which have all seen morphological and molecular efforts come together in large, combined works in recent years. In all of the examined cases the synergistic effect of combining elaborate morphological datasets with ditto molecular clearly outweigh the merits of either data type analysed on its own (even for 'genome size' molecular datasets). It is evident that morphology, far from being obsolete or arcane, still has an immensely important role to play in butterfly (and insect) phylogenetics. Not least because understanding morphology is essential for understanding and evaluating the evolutionary scenarios phylogenetic trees are supposed to illustrate., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

Although the taxonomy of the ca 18 000 species of butterflies and skippers is well known, the family-level relationships are still debated. Here, we present, to our knowledge, the most comprehensive phylogenetic analysis of the superfamilies Papilionoidea, Hesperioidea and Hedyloidea to date based on morphological and molecular data. We reconstructed their phylogenetic relationships using parsimony and Bayesian approaches. We estimated times and rates of diversification along lineages in order to reconstruct their evolutionary history. Our results suggest that the butterflies, as traditionally understood, are paraphyletic, with Papilionidae being the sister-group to Hesperioidea, Hedyloidea and all other butterflies. Hence, the families in the current three superfamilies should be placed in a single superfamily Papilionoidea. In addition, we find that Hedylidae is sister to Hesperiidae, and this novel relationship is supported by two morphological characters. The families diverged in the Early Cretaceous but diversified after the Cretaceous-Palaeogene event. The diversification of butterflies is characterized by a slow speciation rate in the lineage leading to Baronia brevicornis, a period of stasis by the skippers after divergence and a burst of diversification in the lineages leading to Nymphalidae, Riodinidae and Lycaenidae.

The hypoxia-inducible transcription factor (HIF) controls (in an oxygen-dependent manner) the expression of a large number of genes whose products are involved in the response of cells to hypoxia. HIF is an αβ dimer that binds to hypoxia response elements (HREs) in its target genes. Human HIF-α has three isoforms, HIF-1α, HIF-2α and HIF-3α, of which the roles of HIF-3α are largely unknown, although it is usually regarded as a negative regulator of HIF-1α and HIF-2α. The human HIF-3α locus is subject to extensive alternative splicing, leading to at least seven variants. We analyzed here the effects of the long variants and the short variant HIF-3α4 on the hypoxia response. All these variants were found to interact with HIF-β, HIF-1α and HIF-2α. The long HIF-3α variants were localized in the nucleus in hypoxia, while HIF-3α4 was cytoplasmic. Interaction of the HIF-3α variants with HIF-1α inhibited the nuclear translocation of both. None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2. Unexpectedly, siRNA knock-down of the endogenous HIF-3α variants led to downregulation of certain HIF target genes, while overexpression of individual long HIF-3α variants upregulated certain HIF target genes in a variant and target gene-specific manner under conditions in which HIF-β was not a limiting factor. These data indicate that the HIF-3α variants may have more versatile and specific roles in the regulation of the hypoxia response than previously anticipated.

Play Assessment for Group Settings (PAGS) was originally designed to measure the play ability of 2- to 8-year-old children in their natural day-care context and for the use of different professionals. The main purpose of this study was to examine the inter-rater reliability of the PAGS. Twelve raters from different professional backgrounds scored a total of 78 children, both videotaped co-scored cases and individual live cases. The many-faceted Rasch model (MFR) was used to examine the goodness-of-fit of the rater severity estimates. Of the 12 raters, 91.7% were demonstrated to fit the MFR model expectations. Overall the results of this study indicated that the raters scored the PAGS in a reliable way, and that they behaved like independent experts. The separation index (2.09) of the raters indicated that the inter-rater scorings were comparable with each other for practical purposes. Further research on the different response processes of children in different diagnostic groups is needed.

Novel hollow and solid paramecium-like hierarchical Au/Pt bimetallic nanostructures were constructed using goethite as template via a seed-mediated growth method. Transmission electron microscopy (TEM), xi-potential measurement, UV-vis spectroscopy, energy dispersive x-ray spectroscopy (EDS), ICP-AES measurement, x-ray powder diffraction (XRD) and x-ray photoelectron spectroscopy (XPS) were utilized to systematically characterize the bimetallic nanostructures. It is found that the core structure of the paramecium-like bimetallic nanomaterial is closely related to reducing agent. When ascorbic acid is used as reducing agent, goethite serves as in situ sacrificed template and hollow paramecium-like bimetallic structure is obtained. When NH(2)OH.HCl is used, solid nanostructure with preserved goethite core is produced. Heating the reaction solution is necessary to obtain the paramecium-like morphology with rough interconnected Pt cilia shell. The thickness of Pt cilia layer can be controlled by adjusting the molar ratio of H(2)PtCl(6) to Au nanoseeds. The overgrowth of the rough Pt cilia is proposed to be via an autocatalytic and three-dimensional heterogeneous nucleation process first through flower-like morphology. Both the hollow and solid hierarchical paramecium-like Au/Pt bimetallic nanostructures show good catalytic activities.

The hypoxia-inducible transcription factors (HIFs) play a central role in the response of cells to hypoxia. HIFs are alphabeta dimers, the human alpha subunit having three isoforms. HIF-3alpha is unique among the HIF-alpha isoforms in that its gene is subject to extensive alternative splicing. Database analyses have predicted the generation of six HIF-3alpha splice variants that utilize three alternative transcription initiation sites. None of these variants is likely to act as an efficient transcription factor, but some of them have been reported to inhibit HIF-1 and HIF-2 functions. We analyzed here for the first time in detail whether these six variants are indeed generated in various human tissues and cell lines. We identified four novel variants, named here HIF-3alpha7 to HIF-3alpha10, whereas we obtained no evidence for the predicted HIF-3alpha3 and HIF-3alpha5. Distinct differences in the expression patterns of the variants were found between human tissues, the levels being particularly low in many cancer cell lines. Hypoxia upregulated transcription from all three alternative HIF-3alpha promoters. siRNA experiments showed that this induction is mediated specifically by HIF-1 and not by HIF-2. The tissue-specific differences in the expression patterns and levels of the HIF-3alpha variants can be expected to modulate the hypoxia response of various tissues and cell types to different extents during development and in pathological situations. A further level of regulation is brought about by the fact that the levels of the HIF-3alpha transcripts themselves are regulated by hypoxia and by changes in HIF-1 levels., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Recent advances in phosphoproteomics have established powerful tools to analyze phosphorylation events. However, their spatial localization is lost due to sample homogenization procedures prior to the analysis. Imaging mass spectrometry (IMS) has emerged as a method to visualize the spatial distribution of molecules in tissue samples, but its application is still limited to relatively abundant molecules. Due to low phosphorylation stoichiometry, direct detection and imaging of protein phosphorylation by MS has not been achieved yet. Therefore we have developed a novel phosphopeptide enrichment strategy as a potential tool for in situ affinity imaging MS (AIMS). A specific type of titanium dioxide (TiO2)-coated glass slides was designed and validated with casein tryptic digests for their ability to selectively retain phosphopeptides while maintaining their spatial coordination., (Copyright 2009 John Wiley & Sons, Ltd.)

A superhydrophobic material prepared by precipitating calcium phosphate on TiO2 films under in vitro conditions is described. Crystalline calcium phosphate is very porous with octacalcium phosphate as the main phase. The films are made hydrophobic by the surface grafting of a perfluorophosphate surfactant (Zonyl FSE). The as-prepared coatings were strongly hydrophobic, with advancing contact angles exceeding 165 degrees and receding angles exceeding 150 degrees . The formation of the calcium phosphate layer is self-organizing, and the coating is easily functionalized. The material was characterized with dynamic contact angle measurements, SEM, XRD, and XPS. The strong water repellency is explained by the open porous morphology of the calcium phosphate coating together with the successful attachment of the hydrophobic function.

Wnt-4 signaling has been implicated in female development, because its absence leads to partial female to male sex reversal in the mouse. Instead of Mullerian ducts, Wnt-4-deficient females have Wolffian ducts, suggesting a role for androgens in maintaining this single-sex duct type in females. We demonstrate here that testosterone is produced by the ovary of Wnt-4-deficient female embryos and is also detected in the embryonic plasma. Consistent with this, the expression of several genes encoding enzymes in the pathway leading to the synthesis of testosterone in the mouse is induced in the Wnt-4-deficient ovary, including Cyp11a, Cyp17, Hsd3b1, Hsd17b1, and Hsd17b3. Inhibition of androgen action with an antiandrogen, flutamide, during gestation leads to complete degeneration of the Wolffian ducts in 80% of the mutant females and degeneration of the cortical layer that resembles the tunica albuginea in the masculinized ovary. However, androgen action is not involved in the sexually dimorphic organization of endothelial cells in the Wnt-4 deficient ovary, because flutamide did not change the organization of the coelomic vessel. These data imply that Wnt-4 signaling normally acts to suppress testosterone biosynthesis in the female, and that testosterone is the putative mediator of the masculinization phenotype in Wnt-4-deficient females.

The microbiota of the small intestine is poorly known because of difficulties in sampling. In this study, we examined whether the organisms cultured from the jejunum and feces resemble each other. Small-intestinal fluid samples were collected from 22 beagle dogs with a permanent jejunal fistula in parallel with fecal samples. In addition, corresponding samples from seven of the dogs were collected during a 4-week period (days 4, 10, 14, and 28) to examine the stability of the microbiota. In the jejunal samples, aerobic/facultative and anaerobic bacteria were equally represented, whereas anaerobes dominated in the fecal samples. Despite lower numbers of bacteria in the jejunum (range, 10(2) to 10(6) CFU/g) than in feces (range, 10(8) to 10(11) CFU/g), some microbial groups were more prevalent in the small intestine: staphylococci, 64% versus 36%; nonfermentative gram-negative rods, 27% versus 9%; and yeasts, 27% versus 5%, respectively. In contrast, part of the fecal dominant microbiota (bile-resistant Bacteroides spp., Clostridium hiranonis-like organisms, and lactobacilli) was practically absent in the jejunum. Many species were seldom isolated simultaneously from both sample types, regardless of their overall prevalence. In conclusion, the small intestine contains a few bacterial species at a time with vastly fluctuating counts, opposite to the results obtained for the colon, where the major bacterial groups remain relatively constant over time. Qualitative and quantitative differences between the corresponding jejunal and fecal samples indicate the inability of fecal samples to represent the microbiotas present in the upper gut.

Objectives: To study the effects of tamoxifen and toremifene on bone mineral density (BMD) in postmenopausal women with breast cancer., Methods: Seventy patients with stage II-III breast cancer were randomized to start either tamoxifen (n = 36; 20 mg per day) or toremifene (n = 34; 40 mg per day) for 3 years. BMD in the lumbar spine and in the proximal femur was measured by dual-energy X-ray absorptiometry both before and during the treatment and 1 year after the discontinuation of the anti-estrogens., Results: The baseline BMD measurements were comparable between the groups. In 3 years, lumbar BMD decreased by 1.7% in tamoxifen (P = 0.048) and 3.0% in toremifene (P = 0.001) users (ns between the groups), and femoral neck BMD by 0.9% (P = 0.040) and 1.3% (P = ns), respectively. The use of hormone replacement therapy (HRT) until the diagnosis of breast cancer was associated with decreases in lumbar BMD during anti-estrogen regimen (4% at 3 years) in contrast to unchanged lumbar BMD in women with no previous use of HRT. During the 1st year after the cessation of anti-estrogen, lumbar BMD did not change at all in either group whereas femoral BMD decreased in both the groups at the rate of 1.5-3.2%, as expected., Conclusions: We conclude that tamoxifen (20 mg) and toremifene (40 mg) have similar bone-sparing efficacy that in lumbar spine extends up to 1 year after the cessation of these regimens. This effect is not seen in lumbar spine BMD in those postmenopausal women who discontinue HRT at the time of breast cancer diagnosis.

High phytoestrogen intake among Asian women has been thought to explain the low risk of bone fractures in these populations. In a randomized placebo-controlled trial we studied the effects of isoflavonoids on urinary output of the N-terminal cross-linked telopeptide of type I collagen, pyridinoline (Pyr), and deoxypyridinoline (Dpyr) (bone resorption markers) and serum levels of bone-specific alkaline phosphatase and N-terminal and C-terminal procollagen type I (bone formation markers). Fifty-five postmenopausal women with a history of breast cancer used phytoestrogens (114 mg of isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were then crossed over after a 2-month washout period. The markers were measured before and on the last day of each treatment period. Bone resorption was reduced during phytoestrogen use, as reflected in falls in the urinary output of Pyr (9%; P = 0.001) and Dpyr (5%; P = 0.008). Compared with the placebo group, the fall in Dpyr was significant (P = 0.022) and the falls in Pyr (P = 0.084) and N-terminal cross-linked telopeptide of type I collagen (P = 0.082) showed a trend toward significance. Bone formation markers were not affected by this regimen. Thus, isoflavonoid-induced inhibition of bone resorption may contribute to the low risk of osteoporosis in Asian women.

Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant beta-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral beta-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.