Showing papers by "University of Turku published in 2010"

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

Abstract: Background: Age-related physiological changes in the gastrointestinal tract, as well as modifications in lifestyle, nutritional behaviour, and functionality of the host immune system, inevitably affect the gut microbiota, resulting in a greater susceptibility to infections. Methodology/Principal Findings: By using the Human Intestinal Tract Chip (HITChip) and quantitative PCR of 16S rRNA genes of Bacteria and Archaea, we explored the age-related differences in the gut microbiota composition among young adults, elderly, and centenarians, i.e subjects who reached the extreme limits of the human lifespan, living for over 100 years. We observed that the microbial composition and diversity of the gut ecosystem of young adults and seventy-years old people is highly similar but differs significantly from that of the centenarians. After 100 years of symbiotic association with the human host, the microbiota is characterized by a rearrangement in the Firmicutes population and an enrichment in facultative anaerobes, notably pathobionts. The presence of such a compromised microbiota in the centenarians is associated with an increased inflammatory status, also known as inflammageing, as determined by a range of peripheral blood inflammatory markers. This may be explained by a remodelling of the centenarians’ microbiota, with a marked decrease in Faecalibacterium prauznitzii and relatives, symbiotic species with reported anti-inflammatory properties. As signature bacteria of the long life we identified specifically Eubacterium limosum and relatives that were more than ten-fold increased in the centenarians. Conclusions/Significance: We provide evidence for the fact that the ageing process deeply affects the structure of the human gut microbiota, as well as its homeostasis with the host’s immune system. Because of its crucial role in the host physiology and health status, age-related differences in the gut microbiota composition may be related to the progression of diseases and frailty in the elderly population.

A diversity of beta diversities: straightening up a concept gone awry. Part 1. Defining beta diversity as a function of alpha and gamma diversity

Abstract: The term beta diversity has been used to refer to a wide variety of phenomena. Although all of these encompass some kind of compositional heterogeneity between places, many are not related to each other in any predictable way. The present two-part review aims to put the different phenomena that have been called beta diversity into a common conceptual framework, and to explain what each of them measures. In this first part, the focus is on defining a beta component of diversity. This involves deciding what diversity is and how the observed total or gamma diversity (g) is partitioned into alpha (a) and beta (b) components. Several different definitions of ‘‘beta diversity’’ that result from these decisions have been used in the ecological literature. True beta diversity is obtained when the total effective number of species in a dataset (true gamma diversity g) is multiplicatively partitioned into the effective number of species per compositionally distinct

The spectral energy distribution of fermi bright blazars

Abstract: We have conducted a detailed investigation of the broadband spectral properties of the gamma-ray selected blazars of the Fermi LAT Bright AGN Sample (LBAS). By combining our accurately estimated Fermi gamma-ray spectra with Swift, radio, infra-red, optical, and other hard X-ray/gamma-ray data, collected within 3 months of the LBAS data taking period, we were able to assemble high-quality and quasi-simultaneous spectral energy distributions (SED) for 48 LBAS blazars. The SED of these gamma-ray sources is similar to that of blazars discovered at other wavelengths, clearly showing, in the usual log nu-log nu F-nu representation, the typical broadband spectral signatures normally attributed to a combination of low-energy synchrotron radiation followed by inverse Compton emission of one or more components. We have used these SED to characterize the peak intensity of both the low-and the high-energy components. The results have been used to derive empirical relationships that estimate the position of the two peaks from the broadband colors (i.e., the radio to optical, alpha(ro), and optical to X-ray, alpha(ox), spectral slopes) and from the gamma-ray spectral index. Our data show that the synchrotron peak frequency (nu(S)(peak)) is positioned between 10(12.5) and 10(14.5) Hz in broad-lined flat spectrum radio quasars (FSRQs) and between 10(13) and 10(17) Hz in featureless BL Lacertae objects. We find that the gamma-ray spectral slope is strongly correlated with the synchrotron peak energy and with the X-ray spectral index, as expected at first order in synchrotron-inverse Compton scenarios. However, simple homogeneous, one-zone, synchrotron self-Compton (SSC) models cannot explain most of our SED, especially in the case of FSRQs and low energy peaked (LBL) BL Lacs. More complex models involving external Compton radiation or multiple SSC components are required to reproduce the overall SED and the observed spectral variability. While more than 50% of known radio bright high energy peaked (HBL) BL Lacs are detected in the LBAS sample, only less than 13% of known bright FSRQs and LBL BL Lacs are included. This suggests that the latter sources, as a class, may be much fainter gamma-ray emitters than LBAS blazars, and could in fact radiate close to the expectations of simple SSC models. We categorized all our sources according to a new physical classification scheme based on the generally accepted paradigm for Active Galactic Nuclei and on the results of this SED study. Since the LAT detector is more sensitive to flat spectrum gamma-ray sources, the correlation between nu(S)(peak) and gamma-ray spectral index strongly favors the detection of high energy peaked blazars, thus explaining the Fermi overabundance of this type of sources compared to radio and EGRET samples. This selection effect is similar to that experienced in the soft X-ray band where HBL BL Lacs are the dominant type of blazars.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Abstract: Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Psychosocial Risk Factors Associated With Cyberbullying Among Adolescents: A Population-Based Study

Abstract: Context To our knowledge, no population study examining psychosocial and psychiatric risk factors associated with cyberbullying among adolescents exists. Objective To study cross-sectional associations between cyberbullying and psychiatric and psychosomatic problems among adolescents. Design Population-based cross-sectional study. Setting Finland. Participants The sample consists of 2215 Finnish adolescents aged 13 to 16 years with complete information about cyberbullying and cybervictimization. Main Outcome Measures Self-reports of cyberbullying and cybervictimization during the past 6 months. Results In the total sample, 4.8% were cybervictims only, 7.4% were cyberbullies only, and 5.4% were cyberbully-victims. Cybervictim-only status was associated with living in a family with other than 2 biological parents, perceived difficulties, emotional and peer problems, headache, recurrent abdominal pain, sleeping difficulties, and not feeling safe at school. Cyberbully-only status was associated with perceived difficulties, hyperactivity, conduct problems, low prosocial behavior, frequent smoking and drunkenness, headache, and not feeling safe at school. Cyberbully-victim status was associated with all of these risk factors. Among cybervictims, being cyberbullied by a same-sex or opposite-sex adult, by an unknown person, and by a group of people were associated with fear for safety, indicating possible trauma. Conclusions Both cyberbullying and cybervictimization are associated with psychiatric and psychosomatic problems. The most troubled are those who are both cyberbullies and cybervictims. This indicates the need for new strategies for cyberbullying prevention and intervention.

The spitzer survey of stellar structure in galaxies (s^4g)

Abstract: The Spitzer Survey of Stellar Structure in Galaxies (S^4G) is an Exploration Science Legacy Program approved for the Spitzer post–cryogenic mission. It is a volume-, magnitude-, and size-limited (d < 40 Mpc, |b|> 30°,m_(Bcorr) 1') survey of 2331 galaxies using the Infrared Array Camera (IRAC) at 3.6 and 4.5 μm. Each galaxy is observed for 240 s and mapped to ≥ 1:5 × D_(25). The final mosaicked images have a typical 1 σ rms noise level of 0.0072 and 0:0093 MJy sr^-1 at 3.6 and 4.5 μm, respectively. Our azimuthally averaged surface brightness profile typically traces isophotes at μ_(3.6μm (AB)(1σ) ~ 27 mag arcsec^(-2), equivalent to a stellar mass surface density of ~1 M_⊙pc^(-2). S^4G thus provides an unprecedented data set for the study of the distribution of mass and stellar structures in the local universe. This large, unbiased, and extremely deep sample of all Hubble types from dwarfs to spirals to ellipticals will allow for detailed structural studies, not only as a function of stellar mass, but also as a function of the local environment. The data from this survey will serve as a vital testbed for cosmological simulations predicting the stellar mass properties of present-day galaxies. This article introduces the survey and describes the sample selection, the significance of the 3.6 and 4.5 μm bands for this study, and the data collection and survey strategies. We describe the S^4G data analysis pipeline and present measurements for a first set of galaxies, observed in both the cryogenic and warm mission phases of Spitzer. For every galaxy we tabulate the galaxy diameter, position angle, axial ratio, inclination at μ_(3.6μm)(AB) = 25:5, and 26:5 mag arcsec^(-2) (equivalent to ≈μ_B(AB) = 27:2 and 28:2 mag arcsec^(-2), respectively). These measurements will form the initial S^4G catalog of galaxy properties. We also measure the total magnitude and the azimuthally averaged radial profiles of ellipticity, position angle, surface brightness, and color. Finally, using the galaxy-fitting code GALFIT, we deconstruct each galaxy into its main constituent stellar components: the bulge/spheroid, disk, bar, and nuclear point source, where necessary. Together, these data products will provide a comprehensive and definitive catalog of stellar structures, mass, and properties of galaxies in the nearby universe and will enable a variety of scientific investigations, some of which are highlighted in this introductory S^4G survey paper.

Sudden transition between classical and quantum decoherence.

Abstract: We study the dynamics of quantum and classical correlations in the presence of nondissipative decoherence. We discover a class of initial states for which the quantum correlations, quantified by the quantum discord, are not destroyed by decoherence for times $tl\overline{t}$. In this initial time interval classical correlations decay. For $tg\overline{t}$, on the other hand, classical correlations do not change in time and only quantum correlations are lost due to the interaction with the environment. Therefore, at the transition time $\overline{t}$ the open system dynamics exhibits a sudden transition from classical to quantum decoherence regime.

Genome sequence of the model mushroom Schizophyllum commune

Abstract: Much remains to be learned about the biology of mushroom-forming fungi, which are an important source of food, secondary metabolites and industrial enzymes. The wood-degrading fungus Schizophyllum commune is both a genetically tractable model for studying mushroom development and a likely source of enzymes capable of efficient degradation of lignocellulosic biomass. Comparative analyses of its 38.5-megabase genome, which encodes 13,210 predicted genes, reveal the species's unique wood-degrading machinery. One-third of the 471 genes predicted to encode transcription factors are differentially expressed during sexual development of S. commune. Whereas inactivation of one of these, fst4, prevented mushroom formation, inactivation of another, fst3, resulted in more, albeit smaller, mushrooms than in the wild-type fungus. Antisense transcripts may also have a role in the formation of fruiting bodies. Better insight into the mechanisms underlying mushroom formation should affect commercial production of mushrooms and their industrial use for producing enzymes and pharmaceuticals.

Factors driving the adoption of m-learning: An empirical study

Abstract: Even if m-learning is spreading rapidly in many regions of the world, research addressing the driving factors of m-learning adoption is in short supply Built on the Technology Acceptance Model, this paper proposes a hypothesized model of m-learning adoption Employing structural equation modeling technology, the model was assessed based on the data collected from 230 participants using a survey questionnaire Results indicate that perceived near-term/long-term usefulness and personal innovativeness have significant influence on m-learning adoption intention, while perceived long-term usefulness significantly affects the perceived near-term usefulness Personal innovativeness is a predictor of both the perceived ease of use and perceived long-term usefulness as well Of all variables, the perceived long-term usefulness contributes to the most influential predictor of m-learning adoption The model accounts for approximately 608% of the variance of behavioural intention The results indicted that offing high-quality contents complying with students' future targets is key to the success of m-learning in China Both theoretical and practical implications are discussed

Measure for the non-Markovianity of quantum processes

Abstract: Recently, a measure for the non-Markovian behavior of quantum processes in open systems has been developed, which is based on the quantification of the flow of information between the open system and its environment [Phys. Rev. Lett. 103, 210401 (2009)]. The information flow is connected to the rate of change of the trace distance between quantum states, which can be interpreted in terms of the distinguishability of these states. Here, we elaborate the mathematical details of this theory, present applications to specific physical models, and discuss further theoretical and experimental implications as well as relations to alternative approaches proposed recently.

The use of PET in Alzheimer disease

Abstract: In Alzheimer disease (AD), which is the most common cause of dementia, the underlying disease pathology most probably precedes the onset of cognitive symptoms by many years. Thus, efforts are underway to find early diagnostic markers as well as disease-modifying treatments for this disorder. PET enables various brain systems to be monitored in living individuals. In patients with AD, PET can be used to investigate changes in cerebral glucose metabolism, various neurotransmitter systems, neuroinflammation, and the protein aggregates that are characteristic of the disease, notably the amyloid deposits. These investigations are helping to further our understanding of the complex pathophysiological mechanisms that underlie AD, as well as aiding the early and differential diagnosis of the disease in the clinic. In the future, PET studies will also be useful for identifying new therapeutic targets and monitoring treatment outcomes. Amyloid imaging could be useful as early diagnostic marker of AD and for selecting patients for anti-amyloid-beta therapy, while cerebral glucose metabolism could be a suitable PET marker for monitoring disease progression. For the near future, multitracer PET studies are unlikely to be used routinely in the clinic for AD, being both burdensome and expensive; however, such studies are very informative in a research context.

A diversity of beta diversities: straightening up a concept gone awry. Part 2. Quantifying beta diversity and related phenomena

Abstract: The present two-part review aims to put the different phenomena that have been called "beta diversity" over the years into a common conceptual framework and to explain what each of them measures. The first part (Tuomisto 2010) discussed basic definitions of "beta diversity". Each arises from a different way of combining a definition of "diversity" with a definition of its alpha component and with a mathematical relationship between the alpha and gamma components. This second part assumes that an appropriate basic definition of a beta component (which may or may not be true beta diversity) has been chosen, and the focus here will be on how to quantify it for a given dataset. About twenty different approaches have been used for this purpose. It turns out that only two of these approaches accurately quantify the selected beta component: one does so for the entire dataset, and the other for two sampling units at a time. The other approaches actually quantify other phenomena, such as mean species turnover between sampling units, compositional gradient length (with or without reference to an external gradient), distinctness of a focal sampling unit, rate of species accumulation with increasing sampling effort, rate of compositional turnover along an external gradient, or the rate of decay in compositional similarity with increasing geographical distance. Although most of these phenomena can be expressed as a function of a beta component of diversity, they do not equal a beta component of diversity. Many of these derived variables are not even numerically correlated with the beta component on which they are based, which needs to be taken into account when interpreting the results. The effects of sampling decisions when results are extrapolated beyond the available data will also be discussed.

Cardiac Positron Emission Tomography/Computed Tomography Imaging Accurately Detects Anatomically and Functionally Significant Coronary Artery Disease

Abstract: Background—Computed tomography (CT) is increasingly used to detect coronary artery disease, but the evaluation of stenoses is often uncertain. Perfusion imaging has an established role in detecting ischemia and guiding therapy. Hybrid positron emission tomography (PET)/CT allows combination angiography and perfusion imaging in short, quantitative, low-radiation-dose protocols. Methods and Results—We enrolled 107 patients with an intermediate (30% to 70%) pretest likelihood of coronary artery disease. All patients underwent PET/CT (quantitative PET with 15 O-water and CT angiography), and the results were compared with the gold standard, invasive angiography, including measurement of fractional flow reserve when appropriate. Although PET and CT angiography alone both demonstrated 97% negative predictive value, CT angiography alone was suboptimal in assessing the severity of stenosis (positive predictive value, 81%). Perfusion imaging alone could not always separate microvascular disease from epicardial stenoses, but hybrid PET/CT significantly improved this accuracy to 98%. The radiation dose of the combined PET and CT protocols was 9.3 mSv (86 patients) with prospective triggering and 21.8 mSv (21 patients) with spiral CT. Conclusion—Cardiac hybrid PET/CT imaging allows accurate noninvasive detection of coronary artery disease in a symptomatic population. The method is feasible and can be performed routinely with 10 mSv in most patients. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00627172. (Circulation. 2010;122:603-613.)

A consistent terminology for quantifying species diversity? Yes, it does exist

Abstract: The prevailing terminological confusion around the concept ‘diversity’ has hampered accurate communication and caused diversity issues to appear unnecessarily complicated. In fact, a consistent terminology for phenomena related to (species) diversity is already available. When this terminology is adhered to, diversity emerges as an easily understood concept. It is important to differentiate between diversity itself and a diversity index: an index of something is just a surrogate for the thing itself. The conceptual problem of defining diversity also has to be separated from the practical problem of deciding how to adequately quantify diversity for a community of interest. In practice, diversity can be quantified for any dataset where units of observation (such as individuals) have been classified into types (such as species). All that needs to be known is what proportion of the observed units belong to a type of mean abundance. Diversity equals the inverse of this mean, and it quantifies the effective number of the types of interest. In ecology, interest often (but not always) focuses on species diversity. If the dataset consists of (or gets divided into) subunits, then the total effective number of species (gamma diversity) can be partitioned into the effective number of compositionally distinct subunits (beta diversity) and the mean effective number of species per such subunit (alpha diversity). Species richness is related to species diversity, but they are not the same thing; richness does not take the proportional abundances into account and is therefore the actual—rather than the effective—number of types. Most of the phenomena that have been called ‘beta diversity’ in the past do not quantify an effective number of types, so they should be referred to by names other than ‘diversity’ (for example, species turnover or differentiation).

Validation in interpretive management accounting research

Abstract: This paper extends and contributes to emerging debates on the validation of interpretive research (IR) in management accounting. We argue that IR has the potential to produce not only subjectivist, emic understandings of actors’ meanings, but also explanations, characterised by a certain degree of “thickness”. Mobilising the key tenets of the modern philosophical theory of explanation and the notion of abduction, grounded in pragmatist epistemology, we explicate how explanations may be developed and validated, yet remaining true to the core premises of IR. We focus on the intricate relationship between two arguably central aspects of validation in IR, namely authenticity and plausibility. Working on the assumption that validation is an important, but potentially problematic concern in all serious scholarly research, we explore whether and how validation efforts are manifest in IR using two case studies as illustrative examples. Validation is seen as an issue of convincing readers of the authenticity of research findings whilst simultaneously ensuring that explanations are deemed plausible. Whilst the former is largely a matter of preserving the emic qualities of research accounts, the latter is intimately linked to the process of abductive reasoning, whereby different theories are applied to advance thick explanations. This underscores the view of validation as a process, not easily separated from the ongoing efforts of researchers to develop explanations as research projects unfold and far from reducible to mere technicalities of following pre-specified criteria presumably minimising various biases. These properties detract from a view of validation as conforming to pre-specified, stable, and uniform criteria and allow IR to move beyond the “crisis of validity” arguably prevailing in the social sciences.

Profile and competences for the graduating European dentist - update 2009.

Abstract: This paper presents the profile and competences for the European Dentist as approved by the General Assembly of the Association for Dental Education in Europe at its annual meeting held in Helsinki in August 2009. A new taskforce was convened to update the previous document published in 2005. The updated document was then sent to all European Dental Schools, ministries of health, national dental associations and dental specialty associations or societies in Europe. The feedback received was used to improve the document. European dental schools are expected to adhere to the profile and the 17 major competences but the supporting competences may vary in detail between schools. The document will be reviewed once again in 5 years time. Feedback to the newly published document is welcomed and all dental educators are encouraged to draw upon the content of the paper to assist them in harmonising the curriculum throughout Europe with the aim of improving the quality of the dental curriculum.

A comprehensive panel of three-dimensional models for studies of prostate cancer growth, invasion and drug responses.

Abstract: Prostate epithelial cells from both normal and cancer tissues, grown in three-dimensional (3D) culture as spheroids, represent promising in vitro models for the study of normal and cancer-relevant patterns of epithelial differentiation. We have developed the most comprehensive panel of miniaturized prostate cell culture models in 3D to date (n = 29), including many non-transformed and most currently available classic prostate cancer (PrCa) cell lines. The purpose of this study was to analyze morphogenetic properties of PrCa models in 3D, to compare phenotypes, gene expression and metabolism between 2D and 3D cultures, and to evaluate their relevance for pre-clinical drug discovery, disease modeling and basic research. Primary and non-transformed prostate epithelial cells, but also several PrCa lines, formed well-differentiated round spheroids. These showed strong cell-cell contacts, epithelial polarization, a hollow lumen and were covered by a complete basal lamina (BL). Most PrCa lines, however, formed large, poorly differentiated spheroids, or aggressively invading structures. In PC-3 and PC-3M cells, well-differentiated spheroids formed, which were then spontaneously transformed into highly invasive cells. These cell lines may have previously undergone an epithelial-to-mesenchymal transition (EMT), which is temporarily suppressed in favor of epithelial maturation by signals from the extracellular matrix (ECM). The induction of lipid and steroid metabolism, epigenetic reprogramming, and ECM remodeling represents a general adaptation to 3D culture, regardless of transformation and phenotype. In contrast, PI3-Kinase, AKT, STAT/interferon and integrin signaling pathways were particularly activated in invasive cells. Specific small molecule inhibitors targeted against PI3-Kinase blocked invasive cell growth more effectively in 3D than in 2D monolayer culture, or the growth of normal cells. Our panel of cell models, spanning a wide spectrum of phenotypic plasticity, supports the investigation of different modes of cell migration and tumor morphologies, and will be useful for predictive testing of anti-cancer and anti-metastatic compounds.

Comprehensive gene and taxon coverage elucidates radiation patterns in moths and butterflies

Abstract: Lepidoptera (butterflies and moths) represent one of the most diverse animals groups. Yet, the phylogeny of advanced ditrysian Lepidoptera, accounting for about 99 per cent of lepidopteran species, has remained largely unresolved. We report a rigorous and comprehensive analysis of lepidopteran affinities. We performed phylogenetic analyses of 350 taxa representing nearly 90 per cent of lepidopteran families. We found Ditrysia to be a monophyletic taxon with the clade Tischerioidea + Palaephatoidea being the sister group of it. No support for the monophyly of the proposed major internested ditrysian clades, Apoditrysia, Obtectomera and Macrolepidoptera, was found as currently defined, but each of these is supported with some modification. The monophyly or near-monophyly of most previously identified lepidopteran superfamilies is reinforced, but several species-rich superfamilies were found to be para- or polyphyletic. Butterflies were found to be more closely related to ‘microlepidopteran’ groups of moths rather than the clade Macrolepidoptera, where they have traditionally been placed. There is support for the monophyly of Macrolepidoptera when butterflies and Calliduloidea are excluded. The data suggest that the generally short diverging nodes between major groupings in basal non-tineoid Ditrysia are owing to their rapid radiation, presumably in correlation with the radiation of flowering plants.

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Abstract: Porous silicon (PSi) particles have been studied for the effects they elicit in Caco-2 and RAW 264.7 macrophage cells in terms of toxicity, oxidative stress, and inflammatory response. The most suitable particles were then functionalized with a novel 18F label to assess their biodistribution after enteral and parenteral administration in a rat model. The results show that thermally hydrocarbonized porous silicon (THCPSi) nanoparticles did not induce any significant toxicity, oxidative stress, or inflammatory response in Caco-2 and RAW 264.7 macrophage cells. Fluorescently labeled nanoparticles were associated with the cells surface but were not extensively internalized. Biodistribution studies in rats using novel 18F-labeled THCPSi nanoparticles demonstrated that the particles passed intact through the gastrointestinal tract after oral administration and were also not absorbed from a subcutaneous deposit. After intravenous administration, the particles were found mainly in the liver and spleen, indicating...

The design of artificial nestboxes for the study of secondary hole-nesting birds: a review of methodological inconsistencies and potential biases

Abstract: The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines. Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents. However, when comparing results across study sites the use of nestboxes may also introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained. However, the use of nestboxes may also introduce an unconsidered and potentially significant confounding variable due to differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained. Here we review to what extent the characteristics of artificial nestboxes (e.g. size, shape, construction material, colour) are documented in the 'methods' sections of publications involving hole-nesting passer- ine birds using natural or excavated cavities or artificial nestboxes for reproduction and roosting. Despite explicit previ- ous recommendations that authors describe in detail the characteristics of the nestboxes used, we found that the description of nestbox characteristics in most recent publications remains poor and insufficient. We therefore list the types of descriptive data that should be included in the methods sections of relevant manuscripts and justify this by discussing how variation in nestbox characteristics can affect or confound conclusions from nestbox studies. We also propose several recommendations to improve the reliability and usefulness of research based on long-term studies of any secondary hole-nesting species using artificial nestboxes for breeding or roosting.

Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study

Abstract: The perinatal nutritional environment impacts upon the health and well-being of mother and child also in the long term. The aim of the present study was to determine the safety and efficacy of perinatal probiotic-supplemented dietary counselling by evaluating pregnancy outcome and fetal and infant growth during the 24 months' follow-up. Altogether, 256 women were randomised at their first trimester of pregnancy into a control and a dietary intervention group. The intervention group received intensive dietary counselling provided by a nutritionist and were further randomised, double-blind to receive probiotics (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12; diet/probiotics) or placebo (diet/placebo). Firstly, probiotic intervention reduced the frequency of gestational diabetes mellitus (GDM); 13 % (diet/probiotics) v. 36 % (diet/placebo) and 34 % (control); P = 0.003. Secondly, the safety of this approach was attested by normal duration of pregnancies with no adverse events in mothers or children. No significant differences in prenatal or postnatal growth rates among the study groups were detected. Thirdly, distinctive effects of the two interventions were detected; probiotic intervention reduced the risk of GDM and dietary intervention diminished the risk of larger birth size in affected cases; P = 0.035 for birth weight and P = 0.028 for birth length. The results of the present study show that probiotic-supplemented perinatal dietary counselling could be a safe and cost-effective tool in addressing the metabolic epidemic. In view of the fact that birth size is a risk marker for later obesity, the present results are of significance for public health in demonstrating that this risk is modifiable.

IL-17 Immunity in Human Type 1 Diabetes

Abstract: Th17 immunity has been shown to regulate autoimmune diabetes in mice. IL-17 neutralization prevented development of diabetes when given postinitiation of insulitis but not earlier, suggesting interference with the effector phase of the disease. Islet-cell Ag-specific Th17 cells converted into IFN-γ–secreting Th1-like cells and caused diabetes in mice recipients. The role of IL-17 in human type 1 diabetes (T1D) is, however, not established. In this study, we show upregulation of Th17 immunity in peripheral blood T cells from children with T1D. This was characterized by increased IL-17 secretion and expression of IL-17, IL-22, and retinoic acid-related orphan receptor C isoform 2, but also FOXP3 transcripts upon T cell activation in vitro. Also, circulating memory CD4 cells from children with T1D showed the same pattern of IL-17, IL-22 and FOXP3 mRNA upregulation, indicating IL-17 pathway activation in vivo. IL-17–positive T cells appeared to be CD4+ cells expressing TCR-αβ and CCR6, and a subpopulation showed coproduction of IFN-γ. Given the Th17 immunity in T1D, we demonstrated that IL-17 had detrimental effects on human islet cells in vitro; it potentiated both inflammatory and proapoptotic responses. Our findings highlight the role of IL-17 immunity in the pathogenesis of human T1D and point to a potential therapeutic strategy.

Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles

Abstract: To maintain the female reproductive lifespan, the majority of ovarian primordial follicles are preserved in a quiescent state in order to provide ova for later reproductive life. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Here we provide genetic evidence to show that the tumor suppressor tuberous sclerosis complex 1 (Tsc1), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the quiescence of primordial follicles. In mutant mice lacking the Tsc1 gene in oocytes, the entire pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in the oocyte, ending up with follicular depletion in early adulthood and causing premature ovarian failure (POF). We further show that maintenance of the quiescence of primordial follicles requires synergistic, collaborative functioning of both Tsc and PTEN (phosphatase and tensin homolog deleted on chromosome 10) and that these two molecules suppress follicular activation through distinct ways. Our results suggest that Tsc/mTORC1 signaling and PTEN/PI3K (phosphatidylinositol 3 kinase) signaling synergistically regulate the dormancy and activation of primordial follicles, and together ensure the proper length of female reproductive life. Deregulation of these signaling pathways in oocytes results in pathological conditions of the ovary, including POF and infertility.

Ultra-bright optical transients are linked with type Ic supernovae

Abstract: Recent searches by unbiased, wide-field surveys have uncovered a group of extremely luminous optical transients. The initial discoveries of SN 2005ap by the Texas Supernova Search and SCP-06F6 in a deep Hubble pencil beam survey were followed by the Palomar Transient Factory confirmation of host redshifts for other similar transients. The transients share the common properties of high optical luminosities (peak magnitudes ~ -21 to -23), blue colors, and a lack of H or He spectral features. The physical mechanism that produces the luminosity is uncertain, with suggestions ranging from jet-driven explosion to pulsational pair-instability. Here we report the most detailed photometric and spectral coverage of an ultra-bright transient (SN 2010gx) detected in the Pan-STARRS 1 sky survey. In common with other transients in this family, early-time spectra show a blue continuum, and prominent broad absorption lines of O II. However, about 25d after discovery, the spectra developed type Ic supernova features, showing the characteristic broad Fe II and Si II absorption lines. Detailed, post-maximum follow-up may show that all SN 2005ap and SCP-06F6 type transients are linked to supernovae Ic. This poses problems in understanding the physics of the explosions: there is no indication from late-time photometry that the luminosity is powered by 56Ni, the broad lightcurves suggest very large ejected masses, and the slow spectral evolution is quite different from typical Ic timescales. The nature of the progenitor stars and the origin of the luminosity are intriguing and open questions.