Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma.

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.

Exposure to solar ultraviolet radiation is associated with a decreased folate status in women of childbearing age

In vitro studies indicate that folate in collected human blood is vulnerable to degradation after exposure to ultraviolet (UV) radiation. This has raised concerns about folate depletion in individuals with high sun exposure. Here, we investigate the association between personal solar UV radiation exposure and serum folate concentration, using a three-week prospective study that was undertaken in females aged 18–47 years in Brisbane, Australia (153 E, 27 S). Following two weeks of supplementation with 500 μg of folic acid daily, the change in serum folate status was assessed over a 7-day period of measured personal sun exposure. Compared to participants with personal UV exposures of <200 Joules per day, participants with personal UV exposures of 200–599 and >600 Joules per day had significantly higher depletion of serum folate (p = 0.015). Multivariable analysis revealed personal UV exposure as the strongest predictor accounting for 20% of the overall change in serum folate (Standardised B = −0.49; t = −3.75; p = <0.01). These data show that increasing solar UV radiation exposures reduces the effectiveness of folic acid supplementation. The consequences of this association may be most pronounced for vulnerable individuals, such as women who are pregnant or of childbearing age with high sun exposures.

Gelatine methacrylamide-based hydrogels : an alternative three-dimensional cancer cell culture system

Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of the extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized and established as in vitro and in vivo spheroid-based models for ovarian cancer, reflecting the advanced disease stage of patients, with accumulation of multicellular spheroids in the tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly influenced hydrogel stiffness (0.5±0.2kPa to 9.0±1.8kPa) but had little effect on solute diffusion. The diffusion coefficient of 70kDa fluorescein isothiocyanate (FITC)-labelled dextran in 7% GelMA-based hydrogels was only 2.3 times slower compared to water. Hydrogels of medium concentration (5% w/v GelMA) and stiffness (3.4kPa) allowed spheroid formation and high proliferation and metabolic rates. The inhibition of matrix metalloproteinases and consequently ECM degradability reduced spheroid formation and proliferation rates. The incorporation of the ECM components laminin-411 and hyaluronic acid further stimulated spheroid growth within GelMA-based hydrogels. The feasibility of pre-cultured GelMA-based hydrogels as spheroid carriers within an ovarian cancer animal model was proven and led to tumour development and metastasis. These tumours were sensitive to treatment with the anti-cancer drug paclitaxel, but not the integrin antagonist ATN-161. While paclitaxel and its combination with ATN-161 resulted in a treatment response of 33-37.8%, ATN-161 alone had no effect on tumour growth and peritoneal spread. The semi-synthetic biomaterial GelMA combines relevant natural cues with tunable properties, providing an alternative, bioengineered 3-D cancer cell culture in in vitro and in vivo model systems.

Entering the field as a sports coordinator: Negotiating the micropolitics of the profession

The work of French sociologist, anthropologist and philosopher Pierre Bourdieu has been influential across a set of cognate disciplines that can be classified as physical culture studies. Concepts such as field, capital, habitus and symbolic violence have been used as theoretical tools by scholars and students looking to understand the nature and purpose of sport, leisure, physical education and human movement within wider society. Pierre Bourdieu and Physical Culture is the first book to focus on the significance of Bourdieu’s work for, and in, physical culture. Bringing together the work of leading and emerging international researchers, it introduces the core concepts in Bourdieu’s thought and work, and presents a series of fascinating demonstrations of the application of his theory to physical culture studies. A concluding section discusses the inherent difficulties of choosing and using theory to understand the world around us. By providing an in-depth and multi-layered example of how theory can be used across the many and varied components of sport, leisure, physical education and human movement, this book should help all serious students and researchers in physical culture to better understand the importance of social theory in their work.

Prognostic value of BRAF mutations in localized cutaneous melanoma

BACKGROUND: BRAF mutations are frequent in melanoma but their prognostic significance remains unclear. OBJECTIVE: We sought to further evaluate the prognostic value of BRAF mutations in localized cutaneous melanoma. METHODS: We undertook an observational retrospective study of 147 patients with localized invasive (stages I and II) cutaneous melanomas to determine the prognostic value of BRAF mutation status. RESULTS: After a median follow-up of 48 months, patients with localized melanomas with BRAF-mutant melanomas exhibited poorer disease-free survival than those with BRAF-wt genotype (hazard ratio 2.2, 95% confidence interval 1.1-4.3) even after adjustment for Breslow thickness, tumor ulceration, location, age, sex, and tumor mitotic rate. LIMITATIONS: The retrospective design and the small number of events are limitations. CONCLUSIONS: Our findings suggest that reappraisal of clinical treatment approaches for patients with localized melanoma harboring tumors with BRAF mutation might be warranted

Single molecule microscopy in 3D cell cultures and tissues

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy.

Eläkejärjestelmät ja maahanmuutto : poliittisen taloustieteen lähestymistapa

Tässä työssä kysymystä kouluttamattoman maahanmuuton mahdollisesta vaikutuksesta eläkkeiden rahoitettavuuteen ja sitä kautta maahanmuuttopolitiikkaan lähestytään poliittisen taloustieteen näkökulmasta. Tarkastellaan siis sitä, mitkä ikä- ja tuloryhmät hyötyvät kouluttamattomasta maahanmuutosta sen mahdollisesti helpottaessa eläkkeiden maksua ja mitkä eivät ja millaiseen poliittiseen tasapainoon tämä johtaa. Äänestettäessä maahanmuuttopolitiikasta yksilö perustaisi mielipiteensä maahanmuuttopolitiikan liberalisoinnista tai tiukentamisesta siihen, miten maahanmuutto vaikuttaisi hänen omaan etuunsa. Maan väestö jaetaan eläkeläisiin sekä koulutettuihin ja kouluttamattomiin työntekijöihin ja tarkastellaan miten maahanmuutto vaikuttaa näiden ryhmien taloudelliseen hyötyyn. Aluksi tarkastellaan lyhyesti millaisia malleja maahanmuutosta ja eläkejärjestelmän olemassaolon vaikutuksista siihen suhtautumiseen on olemassa. Ensimmäisen johdantoluvun jälkeen käsitellään sitä, miten äänestystulos maahanmuuttopolitiikasta muuttuu mallin oletusten muuttuessa. Työssä tarkastellaan Razinin ja Sadkan (1999) hyvin yksinkertaista mallia, joka sisältää yksinkertaisuutensa takia joitain hyvin rajoittavia oletuksia. Sitten käydään läpi Kriegerin (2004) sekä Razinin ja Sadkan (2000) tekemiä laajennuksia, joissa osasta rajoittavia oletuksia luovutaan ja katsotaan millaisiin muutoksiin tämä johtaa. Työssä tarkastellaan myös Kriegerin (2003) mallia äänestystuloksesta neljässä erilaisessa eläkejärjestelmässä. Tamuran (2006) mallia tarkastellaan näkökulman laajentamiseksi edelleen. Tarkastelun kohteena ei enää ole vain eläkejärjestelmä, vaan myös tulonsiirrot matalapalkka-alojen työntekijöille. Työssä tarkasteltujen artikkeleiden pohjalta näyttää siltä, että erilaisissa eläkejärjestelmissä ja erilaisissa talouksissa elävät yksilöt suhtautuvat maahanmuuttoon eri tavoin sen mukaan, minkä verran he saavat hyötyä siitä. Hyödyn määrään vaikuttavat myös maahanmuuttajien ominaisuudet ja eläkejärjestelmän ominaisuudet, varsinkin se, onko eläkemaksu vai eläke-etuus vakio. Koska maahanmuutto vaikuttaa talouden eri ryhmiin eli kouluttamattomiin ja koulutettuihin työntekijöihin sekä eläkeläisiin eri tavoin, useimmiten yksimielisyyttä maahanmuuttopolitiikasta ei synny.

Takuueläkettä sai huhtikuussa 87 900 eläkeläistä

Kela alkoi maksaa takuueläkettä 1.3.2011. Takuueläke korotti Suomessa asuvan vähimmäiseläkkeen 687,74 euroon. Huhtikuussa takuueläkkeen saajia oli 87 900.

Tilasto Suomen eläkkeensaajista 2009

Tilasto Suomen eläkkeensaajista perustuu Eläketurvakeskuksen ja Kansaneläkelaitoksen rekistereihin. Julkaisua on tuotettu vuodesta 1981 lähtien. Vuosina 1981–1990 kirja julkaistiin erikseen suomen- ja ruotsinkielisenä. Ruotsinkielinen osa sisälsi suppean englanninkielisen liitteen. Vuodesta 1991 lähtien julkaisu on ollut kolmikielinen. Julkaisu sisältää tietoja kaikista työ- ja kansaneläkkeensaajista, eläkkeelle siirtyneistä ja eläkemenosta. Tietoja on kaikista eläkkeensaajista sekä erikseen Suomessa ja ulkomailla asuvista eläkkeensaajista, poikkeuksena eläkkeelle siirtyneet, joista ei ainakaan toistaiseksi tehdä erillistä tilastoa ulkomailla asuvista. Tilasto on ilmestynyt osana Suomen virallista tilastoa vuodesta 2003 lähtien. Laatuseloste on julkaisun liitteessä 1. Julkaisun alussa on kuvaus eläkejärjestelmästä ja eläke-etuuksista sekä tilastossa käytetyistä käsitteistä. Liitteessä 2 on suppea yhteenveto keskeisistä eläkelainsäädännön muutoksista.

Eläkejärjestelmät ja maahanmuutto : poliittisen taloustieteen lähestymistapa

Tässä työssä kysymystä kouluttamattoman maahanmuuton mahdollisesta vaikutuksesta eläkkeiden rahoitettavuuteen ja sitä kautta maahanmuuttopolitiikkaan lähestytään poliittisen taloustieteen näkökulmasta. Tarkastellaan siis sitä, mitkä ikä- ja tuloryhmät hyötyvät kouluttamattomasta maahanmuutosta sen mahdollisesti helpottaessa eläkkeiden maksua ja mitkä eivät ja millaiseen poliittiseen tasapainoon tämä johtaa. Äänestettäessä maahanmuuttopolitiikasta yksilö perustaisi mielipiteensä maahanmuuttopolitiikan liberalisoinnista tai tiukentamisesta siihen, miten maahanmuutto vaikuttaisi hänen omaan etuunsa. Maan väestö jaetaan eläkeläisiin sekä koulutettuihin ja kouluttamattomiin työntekijöihin ja tarkastellaan miten maahanmuutto vaikuttaa näiden ryhmien taloudelliseen hyötyyn. Aluksi tarkastellaan lyhyesti millaisia malleja maahanmuutosta ja eläkejärjestelmän olemassaolon vaikutuksista siihen suhtautumiseen on olemassa. Ensimmäisen johdantoluvun jälkeen käsitellään sitä, miten äänestystulos maahanmuuttopolitiikasta muuttuu mallin oletusten muuttuessa. Työssä tarkastellaan Razinin ja Sadkan (1999) hyvin yksinkertaista mallia, joka sisältää yksinkertaisuutensa takia joitain hyvin rajoittavia oletuksia. Sitten käydään läpi Kriegerin (2004) sekä Razinin ja Sadkan (2000) tekemiä laajennuksia, joissa osasta rajoittavia oletuksia luovutaan ja katsotaan millaisiin muutoksiin tämä johtaa. Työssä tarkastellaan myös Kriegerin (2003) mallia äänestystuloksesta neljässä erilaisessa eläkejärjestelmässä. Tamuran (2006) mallia tarkastellaan näkökulman laajentamiseksi edelleen. Tarkastelun kohteena ei enää ole vain eläkejärjestelmä, vaan myös tulonsiirrot matalapalkka-alojen työntekijöille. Työssä tarkasteltujen artikkeleiden pohjalta näyttää siltä, että erilaisissa eläkejärjestelmissä ja erilaisissa talouksissa elävät yksilöt suhtautuvat maahanmuuttoon eri tavoin sen mukaan, minkä verran he saavat hyötyä siitä. Hyödyn määrään vaikuttavat myös maahanmuuttajien ominaisuudet ja eläkejärjestelmän ominaisuudet, varsinkin se, onko eläkemaksu vai eläke-etuus vakio. Koska maahanmuutto vaikuttaa talouden eri ryhmiin eli kouluttamattomiin ja koulutettuihin työntekijöihin sekä eläkeläisiin eri tavoin, useimmiten yksimielisyyttä maahanmuuttopolitiikasta ei synny.

Falsche Fische – ein Bericht über die Schwierigkeiten der Identifizierung einer „Seezunge“

In the last years German food control laboratories have established proof of a significant number of cases of incorrectly labelled flatfish on the German market. A flatfish offered as sole (Solea vulgaris) in Southern Germany served as an example for mislabelled flatfish and for the difficulties food control laboratories may encounter and to identify products of unknown origin. Morphometric and meristic examination, as well as isoelectric focusing of sarcoplasmic proteins, PCR-based DNA-analysis failed to identify the fish. By using these methods, it only could be excluded that the fish belonged to the species of Solea vulgaris or another described flatfish species. DNA sequencing of an amplicon gave a sequence identical to a sequence in GenBank, which, however, turned out to be incorrectly assigned to Solea vulgaris. More research about characterization and identification of tropical flatfish is recommended, because of the growing importance of these fishes for the European market.

Cereal products for specific dietary requirements. Evaluation and improvement of technological and nutritional properties of gluten free raw materials and end products

Coeliac disease is one of the most common food intolerances worldwide and at present the gluten free diet remains the only suitable treatment. A market overview conducted as part of this thesis on nutritional and sensory quality of commercially available gluten free breads and pasta showed that improvements are necessary. Many products show strong off-flavors, poor mouthfeel and reduced shelf-life. Since the life-long avoidance of the cereal protein gluten means a major change to the diet, it is important to also consider the nutritional value of products intending to replace staple foods such as bread or pasta. This thesis addresses this issue by characterising available gluten free cereal and pseudocereal flours to facilitate a better raw material choice. It was observed that especially quinoa, buckwheat and teff are high in essential nutrients, such as protein, minerals and folate. In addition the potential of functional ingredients such as inulin, β-glucan, HPMC and xanthan to improve loaf quality were evaluated. Results show that these ingredients can increase loaf volume and reduce crumb hardness as well as rate of staling but that the effect diverges strongly depending on the bread formulation used. Furthermore, fresh egg pasta formulations based on teff and oat flour were developed. The resulting products were characterised regarding sensory and textural properties as well as in vitro digestibility. Scanning electron and confocal laser scanning microscopy was used throughout the thesis to visualise structural changes occurring during baking and pasta making

Fundamental studies of sourdoughs fermented with Weissella cibaria and Lactobacillus plantarum: influence on baking characteristics, sensory profiles and in vitro starch digestibility of gluten-free breads

The application of sourdough can improve texture, structure, nutritional value, staling rate and shelf life of wheat and gluten-free breads. These quality improvements are associated with the formation of organic acids, exopolysaccharides (EPS), aroma or antifungal compounds. Initially, the suitability of two lactic acid bacteria strains to serve as sourdough starters for buckwheat, oat, quinoa, sorghum and flours was investigated. Wheat flour was chosen as a reference. The obligate heterofermentative lactic acid bacterium (LAB) Weissella cibaria MG1 (Wc) formed the EPS dextran (a α-1,6-glucan) from sucrose in situ with a molecular size of 106 to 107 kDa. EPS formation in all breads was analysed using size exclusion chromatography and highest amounts were formed in buckwheat (4 g/ kg) and quinoa sourdough (3 g/ kg). The facultative heterofermentative Lactobacillus plantarum FST1.7 (Lp) was identified as strong acidifier and was chosen due to its ubiquitous presence in gluten-free as well as wheat sourdoughs (Vogelmann et al. 2009). Both Wc and Lp, showed highest total titratable acids in buckwheat (16.8 ml; 26.0 ml), teff (16.2 ml; 24.5 ml) and quinoa sourdoughs (26.4 ml; 35.3 ml) correlating with higher amounts of fermentable sugars and higher buffering capacities. Sourdough incorporation reduced the crumb hardness after five days of storage in buckwheat (Wc -111%), teff (Wc -39%) and wheat (Wc -206%; Lp -118%) sourdough breads. The rate of staling (N/ day) was reduced in buckwheat (Ctrl 8 N; Wc 3 N; Lp 6 N), teff (Ctrl 13 N; Wc 9 N; Lp 10 N) and wheat (Ctrl 5 N; Wc 1 N; Lp 2 N) sourdough breads. Bread dough softening upon Wc and Lp sourdough incorporation accounted for increased crumb porosity in buckwheat (+10.4%; +4.7), teff (+8.1%; +8.3%) and wheat sourdough breads (+8.7%; +6.4%). Weissella cibaria MG1 sourdough improved the aroma quality of wheat bread but had no impact on aroma of gluten-free breads. Microbial shelf life however, was not prolonged in any of the breads regardless of the starter culture used. Due to the high prevalence of insulin-dependent diabetes mellitus particular amongst coeliac patients, glycaemic control is of great (Berti et al. 2004). The in vitro starch digestibility of gluten-free breads with and without sourdough addition was analysed to predict the GI (pGI). Sourdough can decrease starch hydrolysis in vitro, due to formation of resistant starch and organic acids. Predicted GI of gluten-free control breads were significantly lower than for the reference white wheat bread (GI=100). Starch granule size was investigated with scanning electron microscopy and was significantly smaller in quinoa flour (<2 μm). This resulted in higher enzymatic susceptibility and hence higher pGI for quinoa bread (95). Lowest hydrolysis indexes for sorghum and teff control breads (72 and 74, respectively) correlate with higher gelatinisation peak temperatures (69°C and 71°C, respectively). Levels of resistant starch were not increased by addition of Weissella cibaria MG1 (weak acidifier) or Lactobacillus plantarum FST1.7 (strong acidifier). The pGI was significantly decreased for both wheat sourdough breads (Wc 85; Lp 76). Lactic acid can promote starch interactions with gluten hence decreasing starch susceptibility (Östman et al. 2002). For most gluten-free breads, the pGI was increased upon sourdough addition. Only sorghum and teff Lp sourdough breads (69 and 68, respectively) had significantly decreased pGI. Results suggest that the increase of starch hydrolysis in gluten-free breads was related to mechanism other than presence of organic acids and formation of resistant starch.

Fundamental studies on the application of enzymes when brewing with unmalted oats and sorghum

The use of unmalted oats or sorghum in brewing has great potential for creating new beer types/flavors and saving costs. However, the substitution of barley malt with oat or sorghum adjunct is not only innovative but also challenging due to their specific grain characteristics. The overall objectives of this Ph.D. project were: 1) to investigate the impact of various types and levels of oats or sorghum on the quality/processability of mashes, worts, and beers; 2) to provide solutions as regards the application of industrial enzymes to overcome potential brewing problems. For these purposes, a highly precise rheological method using a controlled stress rheometer was developed and successfully applied as a tool for optimizing enzyme additions and process parameters. Further, eight different oat cultivars were compared in terms of their suitability as brewing adjuncts and two very promising types identified. In another study, the limitations of barley malt enzymes and the benefits of the application of industrial enzymes in high-gravity brewing with oats were determined. It is recommended to add enzymes to high-gravity mashes when substituting 30% or more barley malt with oats in order to prevent filtration and fermentation problems. Pilot-scale brewing trials using 10–40% unmalted oats revealed that the sensory quality of oat beers improved with increasing adjunct level. In addition, commercially available oat and sorghum flours were implemented into brewing. The use of up to 70% oat flour and 50% sorghum flour, respectively, is not only technically feasible but also economically beneficial. In a further study on sorghum was demonstrated that the optimization of industrial mashing enzymes has great potential for reducing beer production costs. A comparison of the brewing performance of red Italian and white Nigerian sorghum clearly showed that European grown sorghum is suitable for brewing purposes; 40% red sorghum beers were even found to be very low in gluten.