Transcriptomic Complexity of Aspergillus terreus Velvet Gene Family under the Influence of Butyrolactone I

Filamentous fungi of the Ascomycota phylum are known to contain a family of conserved conidiation regulating proteins with distinctive velvet domains. In Aspergilli, this velvet family includes four proteins, VeA, VelB, VelC and VosA, and is involved in conidiation and secondary metabolism along with a global regulator LaeA. In A. terreus, the overexpression of LaeA has been observed to increase the biogenesis of the harmaceutically-important secondary metabolite, lovastatin, while the role of the velvet family has not been studied. The secondary metabolism and conidiation of A. terreus have also been observed to be increased by butyrolactone I in a quorum-sensing manner. An enlightenment of the interplay of these regulators will give potential advancement to the industrial use of this fungus, as well as in resolving the pathogenic features. In this study, the Aspergillus terreus MUCL 38669 transcriptome was strand-specifically sequenced to enable an in-depth gene expression analysis to further investigate the transcriptional role of butyrolactone I in these processes. The sequenced transcriptome revealed intriguing properties of the velvet family transcripts, including the regulator laeA, and uncovered the velC gene in A. terreus. The reliability refining microarray gene expression analysis disclosed a positive regulatory role for butyrolactone I in laeA expression, as well as an influence on the expression of the canonical conidiation-regulating genes under submerged culture. All of this supports the suggested regulative role of butyrolactone I in A. terreus secondary metabolism, as well as conidiation

A time-resolved fluorescence immunoassay for the measurement of testosterone in saliva: Monitoring of testosterone replacement therapy with testosterone buciclate

Monitoring of testosterone replacement therapy requires a reliable method for testosterone measurement. Determination of salivary testosterone, which reflects the hormone's biologically active plasma fraction, is a superior technique for this purpose. The aim of the present study was to establish a new sensitive time-resolved fluorescence immunoassay for the accurate measurement of testosterone levels in saliva and to validate it by monitoring testosterone replacement therapy in eight hypogonadal men. A clinical phase I- study with the new ester testosterone buciclate was performed to search for new testosterone preparations to produce constant serum levels in the therapy of male hypogonadism. After two control examinations eight male patients with primary hypogonadism were randomly assigned to two treatment groups (n = 2x4) and given single doses of either 200 mg (group I) or 600 mg (group II) testosterone buciclate intramuscularly. Saliva and blood samples were obtained 1, 2, 3, 5 and 7 days post injection and then weekly for three months. The time-resolved fluorescence immunoassay for salivary testosterone shows a detection limit of 16 pmol/l, an intra-assay CV of 8.9% (at a testosterone concentration of 302 pmol/l), an inter-assay CV of 8.7% (at a testosterone concentration of 305 pmol/l) and a good correlation with an established radioimmunsassay of r = 0.89. The sample volume required by this method is only 180 mu l for extraction and duplicate determination. The assay procedure requires no more than three hours. In group I (200 mg) testosterone did not increase to normal levels either in saliva or in serum. However, in group II, androgen levels increased significantly and were maintained in the normal range for up to 12 weeks with maximal salivary testosterone levels of 303 +/- 18 pmol/l (mean+/-SE) and maximal testosterone levels of 13.1 +/- 0.9 nmol/l (mean+/-SE) in serum in study week 6 and 7. The time-resolved fluorescence immunoassay for salivary testosterone provides a useful tool for monitoring androgen status in men and women and is well suited for the follow-up of testosterone replacement therapy on an outpatient basis. The long-acting ester testosterone buciclate is a promising agent for substitution therapy of male hypogonadism and in combination with testosterone monitoring in saliva offers an interesting new perspective for male contraception

A Potential Biofilm Metabolite Signature for Caries Activity - A Pilot Clinical Study

BACKGROUND: This study's aim was to compare the dental biofilm metabolite-profile of caries-active (N=11) or caries-free (N=4) children by gas chromatography-mass spectrometry (GC/MS) analyses. METHODS: Samples collected after overnight fasting, with or without a previous glucose rinse, were combined for each child based on the caries status of the site, re-suspended in ethanol and analyzed by GC/MS. RESULTS: Biofilm from caries-active sites exhibited a different chromatographic profile compared to caries-free sites. Qualitative and quantitative analysis suggested a special cluster of branched alcohols and esters present at substantially higher intensity in biofilms of caries-active sites. CONCLUSIONS: This pilot study indicates that there are metabolites present in the biofilm which have the potential to provide a characteristic metabolomics signature for caries activity

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation

Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated.We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semi-quantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p<0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAV-AS group, compared with the TAV-AS and CBAV-AR groups (both p<0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p<0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35).Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Thermal and porosity properties of meteorites : A compilation of published data and new measurements

We report direct measurements of thermal diffusivity and conductivity at room temperature for 38 meteorite samples of 36 different meteorites including mostly chondrites, and thus almost triple the number of meteorites for which thermal conductivity is directly measured. Additionally, we measured porosity for 34 of these samples. Thermal properties were measured using an optical infrared scanning method on samples of cm-sizes with a flat, sawn surface. A database compiled from our measurements and literature data suggests that thermal diffusivities and conductivities at room temperature vary largely among samples even of the same petrologic and chemical type and overlap among, for example, different ordinary chondrite classes. Measured conductivities of ordinary chondrites vary from 0.4 to 5.1 W m(-1) K-1. On average, enstatite chondrites show much higher values (2.33-5.51 W m(-1) K-1) and carbonaceous chondrites lower values (0.5-2.55 W m(-1) K-1). Mineral composition (silicates versus iron-nickel) and porosity control conductivity. Porosity shows (linear) negative correlation with conductivity. Variable conductivity is attributed to heterogeneity in mineral composition and porosity by intra- and intergranular voids and cracks, which are important in the scale of typical meteorite samples. The effect of porosity may be even more significant for thermal properties than that of the metal content in chondrites.Peer reviewe

Yrittäjyys, yrittäjyyskasvatus ja uusiliberalismi:yrittäjyyskasvattajien näkemyksiä

Tiivistelmä. Tämä pro gradu -tutkielma käsittelee yrittäjyyttä, yrittäjyyskasvatusta ja uusliberalismia. Teoreettisessa viitekehyksessä eritellään yrittäjyyden, yrittäjyyskasvatuksen sekä uusliberalismin käsitettä, termistöä ja historiaa. Tutkimuksessa valotetaan yrittäjyyden käsitettä ja historiaa, uusliberalismin syntymistä ja näiden vaikutuksesta kehittynyttä yrittäjyyskasvatusta. Lisäksi eritellään myös yrittäjyyskasvatuksen tietä Suomen koulujärjestelmään; kuinka yhteiskunnallinen päätöksenteko on vaikuttanut siihen, ja kuinka yrittäjyyskasvatuksen puolestaan halutaan vaikuttavan yhteiskuntaan tulevaisuudessa. Tutkimuksen empiirisessä osiossa on haastateltu kahdeksaa Oulun alueen yrittäjyyskasvatuksen ammattilaista viidessä eri haastattelussa ja pyritty selvittämään heidän näkemyksiään yrittäjyyskasvatuksesta, tulevaisuuden työelämässä vaadittavista taidoista sekä uusliberalismista. Tutkimusaineisto on kerätty teemahaastatteluilla. Tutkimus on toteutettu laadullisena fenomenografisena tutkimuksena, jossa keskiössä on ollut tutkia, luonnehtia ja ymmärtää tutkittavien erilaisia käsityksiä tutkimusaiheesta. Aineisto on analysoitu käyttäen neliportaista fenomenografista analyysia. Tutkimustulokset on jaoteltu tutkimuksessa kolmeen kuvauskategoriaan, jotka ovat 1) Yrittäjyyskasvatus, 2) Tulevaisuuden työelämätaidot sekä 3) Yhteiskunnallinen kehitys. Tuloksista voidaan todeta, että käytännön yrittäjyyskasvatus noudattelee hyvin pitkälti niitä opetusmetodeja, joita sen hallinnollisissa asiakirjoissa halutaankin noudattavan. Käytännön yrittäjyyskasvatus nähdään olevan hyvin työelämälähtöistä. Yrittäjyyskasvattajien näkemykset tulevaisuuden työelämätaidoista ovat hyvin yhteneväiset niiden valmiuksien kanssa, joita he yrittäjyyskasvatuksella pyrkivät oppilaille ja opiskelijoille välittämään. Koulujärjestelmä nähdään osana yhteiskuntaa ja sen tiedostetaan olevan alttiina poliittisille trendeille, muun muassa uusliberalismille. Uusliberalismi jakaa haastatteluissa mielipiteitä. Tuloksissa voidaan nähdä vastakkainasettelua perinteisten suomalaisten hyvinvointivaltion arvojen sekä uusliberalismin välillä. Tutkimuksen eri vaiheet on kuvattu kattavasti ja läpinäkyvästi, jotta lukija voi arvioida tutkimuksen luotettavuutta parhaalla mahdollisella tavalla

Genetic Testing and the Spirit of Laws : study on legal regulation on genetic tests

This study examines legal regulation on genetic testing in the health care setting and on the consumer markets, and the various factors behind. Genetic applications for human health hold great promises for precision medicine, but raise also morally sensitive and controversial issues. Values and moral need to be integrated when addressing law in this field, thus the relationship of law, moral, and bioethics is analyzed. The regulatory scene in the biomedical field is complex with transnational laws, ethical codes, guidelines, and other policy papers. For many, the picture is unclear which maintains insecurity in practice, as it may be challenging to separate law from non-law. The notion of legal pluralism is particularly interesting in this context, and is discussed in the study. To manage the scene and pluralism, this study aims to map relevant laws, and other quasi-normative instruments. The study is based on four previously published articles, the contents of which are updated to the current situation in terms of legal regulation (until May 31, 2020) and scientific progress, and further elaborated with a wide range of multidisciplinary literature and court cases, particularly in light of ECtHR’s praxis and argumentation on the margin of appreciation. The methodology is partly legal dogmatic, partly reasoning and multidisciplinary argumentation in the realm of current legal theories. Europe is fragmented in legal approaches to many treatments. Services, goods, and people cross borders. EU and Council of Europe have influence on the member states’ regulation, even though they enjoy wide margin of appreciation in many health-related matters. Biomedical field is dynamic and evolving in science. Therefore, regulatory approaches need careful assessment in terms of need and accuracy, so that basic research and adoption of new applications are not unnecessary hindered. Moral issues and concrete physical risks need to be addressed, but shall not be confused with each other in this regard. The claim for the 4th generation human rights, biorights, aims to protect peoples’ genetic integrity against rapid biomedical progress. The need for and the legitimacy of biomedical regulation should be addressed in multidisciplinary fora, for which bioethics provides a good platform. However, methodology is needed to support its normative suggestions. Moral philosophy can be seen as to lay the ground and concepts for bioethics, thus enabling proper elaboration of moral beliefs.Oikeustieteellinen väitöskirja ’Geenitestaus ja lakien henki’ käsittelee lääketieteellisten ja kuluttajille tarjottavien geenitestien oikeudellista sääntelyä ja siihen vaikuttavia tekijöitä. Genetiikkaa eli perinnöllisyystiedettä on käytetty jo pitkään terveydenhuollossa. Geenitiedon jakaminen kansainvälisesti kliinisine oirekuvineen on mahdollistanut monien sairauksien diagnosoinnin, uudelleen luokittelun ja lisääntyvän näytön karttumisen tietyn geneettisen ominaisuuden ja kliinisen oireiston välillä. Kuluttajille terveystarkoituksia varten tarjottavat geenitestit ovat jääneet pääosin terveydenhuollon lainsäädännön soveltamisalan ulkopuolelle, mutta niillä voi olla vaikutuksia myös terveyspalvelujärjestelmän toimintaan. Genetiikan kehittyessä siihen liittyvät laadulliset ja eettiset kysymykset tuovat painetta lainsäädäntöä kohtaan. Tutkimus on ajankohtainen, koska hallituksen tavoitteena on säätää genomilaki ja perustaa genomikeskus Suomeen genomitiedon tehokkaaksi, yhdenvertaiseksi ja vastuulliseksi hyödyntämiseksi terveydenhuollossa. Geneettiset sovellukset herättävät toivoa tuodessaan uusia mahdollisuuksia täsmälääketieteeseen. Toisaalta ne huolestuttavat joitakin tahoja, jotka katsovat, että ihminen leikkii jumalaa puuttuessaan lajin luonnolliseen kehitykseen. Genetiikkaan kohdistuu arvoihin ja moraaliin liittyviä näkemyksiä ja uskomuksia. Genetiikan mahdollisuuksia ja rajoja ei riittävästi ymmärretä, mikä johtaa geenitiedon perusteettomaan mystifiointiin. Tutkimuksessa käydään läpi geenitestaukseen soveltuvaa lainsäädäntöä sekä mm. lääkintä- ja bio-oikeuden kehitystä ja suhdetta bioetiikkaan. Biolääketiede tarjoaa erinomaisen alustan oikeudellisen pluralismin tutkimukselle oikeuden ja moraalin rajapinnalla. Tarkastelu ulottuu eurooppalaiseen oikeusjärjestelmään, johon luetaan Euroopan unioni ja Euroopan neuvosto. Moniarvoisessa Euroopassa lainsäätäminen on haastavaa. Sääntelyn tarpeellisuutta arvioitaessa pitää erottaa arvopohjainen, moraaliuskomuksiin perustuva ja riskipohjainen, tieteelliseen epävarmuuteen perustuva lähestyminen