Nanovesicles from Malassezia sympodialis and Host Exosomes Induce Cytokine Responses – Novel Mechanisms for Host-Microbe Interactions in Atopic Eczema

BACKGROUND: Intercellular communication can occur via the release of membrane vesicles. Exosomes are nanovesicles released from the endosomal compartment of cells. Depending on their cell of origin and their cargo they can exert different immunoregulatory functions. Recently, fungi were found to produce extracellular vesicles that can influence host-microbe interactions. The yeast Malassezia sympodialis which belongs to our normal cutaneous microbial flora elicits specific IgE- and T-cell reactivity in approximately 50% of adult patients with atopic eczema (AE). Whether exosomes or other vesicles contribute to the inflammation has not yet been investigated. OBJECTIVE: To investigate if M. sympodialis can release nanovesicles and whether they or endogenous exosomes can activate PBMC from AE patients sensitized to M. sympodialis. METHODS: Extracellular nanovesicles isolated from M. sympodialis, co-cultures of M. sympodialis and dendritic cells, and from plasma of patients with AE and healthy controls (HC) were characterised using flow cytometry, sucrose gradient centrifugation, Western blot and electron microscopy. Their ability to stimulate IL-4 and TNF-alpha responses in autologous CD14, CD34 depleted PBMC was determined using ELISPOT and ELISA, respectively. RESULTS: We show for the first time that M. sympodialis releases extracellular vesicles carrying allergen. These vesicles can induce IL-4 and TNF-α responses with a significantly higher IL-4 production in patients compared to HC. Exosomes from dendritic cell and M. sympodialis co-cultures induced IL-4 and TNF-α responses in autologous CD14, CD34 depleted PBMC of AE patients and HC while plasma exosomes induced TNF-α but not IL-4 in undepleted PBMC. CONCLUSIONS: Extracellular vesicles from M. sympodialis, dendritic cells and plasma can contribute to cytokine responses in CD14, CD34 depleted and undepleted PBMC of AE patients and HC. These novel observations have implications for understanding host-microbe interactions in the pathogenesis of AE

Soft Drink, Software and Softening of Teeth – a Case Report of Tooth Wear in the Mixed Dentition Due to a Combination of Dental Erosion and Attrition

This case report describes a 9-year-old boy with severe tooth wear as a result of drinking a single glass of soft drink per day. This soft drink was consumed over a period of one to two hours, while he was gaming intensively on his computer. As a result, a deep bite, enamel cupping, sensitivity of primary teeth and loss of fillings occurred. Therefore, dentists should be aware that in patients who are gaming intensively, the erosive potential of soft drinks can be potentiated by mechanical forces leading to excessive tooth wear

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Security lies in obedience - Voices of young women of a slum in Pakistan

<p>Abstract</p> <p>Background</p> <p>Existing literature shows that young people, especially women, have poor knowledge about sexuality and reproductive health. Many of the difficulties young women experience are related to beliefs and expectations in society making them more vulnerable to reproductive ill health. The objective of this study was to explore how young women living in a slum in Islamabad are prepared for marriage and how they understand and perceive their transition to marriage and the start of sexual and childbearing activity.</p> <p>Methods</p> <p>Twenty qualitative interviews and three focus group discussions were conducted with young women residing in a slum of Islamabad. Content analysis was used to explore how the participants represented and explained their situation and how decisions about their marriage were made.</p> <p>Results</p> <p>The main theme identified was <it>security lies in obedience</it>. The two sub-themes contributing to the main theme were <it>socialization into submissiveness </it>and <it>transition into adulthood in silence</it>. The theme and the sub-themes illustrate the situation of young women in a poor setting in Pakistan.</p> <p>Conclusion</p> <p>The study demonstrates how, in a culture of silence around sexuality, young women's socialization into submissiveness lays the foundation for the lack of control over the future reproductive health that they experience.</p

Source localization of reaction-diffusion models for brain tumors

We propose a mathematically well-founded approach for locating the source (initial state) of density functions evolved within a nonlinear reaction-diffusion model. The reconstruction of the initial source is an ill-posed inverse problem since the solution is highly unstable with respect to measurement noise. To address this instability problem, we introduce a regularization procedure based on the nonlinear Landweber method for the stable determination of the source location. This amounts to solving a sequence of well-posed forward reaction-diffusion problems. The developed framework is general, and as a special instance we consider the problem of source localization of brain tumors. We show numerically that the source of the initial densities of tumor cells are reconstructed well on both imaging data consisting of simple and complex geometric structures

Multiyear Climate Variability and Dengue—El Niño Southern Oscillation, Weather, and Dengue Incidence in Puerto Rico, Mexico, and Thailand: A Longitudinal Data Analysis

Michael Johansson and colleagues use wavelet analysis to show that there is limited evidence for a multiyear relationship between climate and dengue incidence in Puerto Rico, Mexico, and Thailand

"Who am I? Where am I?" Experiences of married young women in a slum in Islamabad, Pakistan

Background: According to the cultural tradition in Pakistan, young women belonging to poor families should marry shortly after menarche. However, existing data show that young people, especially women, are not prepared for sexual life and have poor knowledge about sexuality and reproductive health. Many of the difficulties young women experience are related to beliefs and expectations in the society related to their reproductive roles making them more vulnerable to reproductive ill health. Aim: The study explores the preparedness of young women for married life (communicating with spouse, initiation of sexual activity and child bearing) and ability to negotiate in marriage with spouse on number of children to have and on contraceptive use. Methods: In order to obtain an in-depth understanding of young women’s lives qualitative and quantitative approaches were used. Three qualitative studies using narrative and content analysis were carried out in a slum setting in the outskirts of Islamabad city in Pakistan. Married young women (I), unmarried young women (II) and parents (III) were selected with the help of a community worker. Young married women were interviewed three times at different occasions. Narrative structuring was used to explore how the participants represented their situation. In addition twenty qualitative interviews and three focus group discussions were conducted with young unmarried women (II). Twenty-five parents participated in four gender specific focus group discussions (III). Content analysis was used for analysis of study II and III. For the quantitative study (IV), a subset of 1803 married young women aged 15-24 years was drawn from a nationally representative adolescent and youth survey conducted in Pakistan in 2001-2002 by the Population Council. Regression models were used for analysing the following outcomes: reported agreement with spouse on the number of children to have, current use of contraceptives, intention to use contraceptives in the future and the time elapsed between marriage and the first contraceptive use. Key co-variates of interest were variables that measure the involvement of young women in their marriage as having a say in selection of spouse, mobility outside the household, social role and decision making in their homes. Results: The main theme in all the qualitative studies was ‘socialisation of young women into submissiveness’. For the married young women two themes were identified a) submissive-accepting and b) submissive-victims. The married young women who belonged to the accepting group lived under compromised conditions but described themselves as satisfied with their situation. Women belonging to the victimized group experienced physical and verbal abuse for their inability to cope with the duties of a wife, caretaker of the home and bearer of children. Their situation was compounded by the power dynamics within the household (I). For the unmarried young women the main theme identified was security lies in obedience. The two sub-themes contributing to the main theme were socialisation into submissiveness and transition into adulthood in silence (II). The theme and the sub-themes illustrate the situation of young women in a poor setting in Pakistan. The main theme identified in the study with the parents was ‘Good parents’ strive to raise ‘innocent daughters’. The three sub-themes contributing to the main theme were: a daughter - a responsibility and a burden, social and sexual innocence and parents’ roles in the preparation for marriage. The theme and the sub-themes illustrate how the parents saw themselves as responsible for raising ‘innocent daughters’ and arranging good marriages (III). The quantitative study on the married young women showed that having a say in the selection of spouse at the time of marriage was significantly associated with agreeing with spouse over the number of children to have, intention to use contraceptives and the time between marriage and first contraceptive use. These relationships existed after controlling for education, socioeconomic status, mobility outside of house and decision making in the home (IV). Conclusions: In a culture of silence around sexuality, young women’s socialisation into submissiveness lays the foundation for the lack of control over their future reproductive health (I and II). The parents realised, though, that bringing up daughters for marriage requires not only obedience, but also building confidence and knowledge during their childhood (III). Women who had decision making freedom in their parental home carried this ability with them into marriage in their new home and were better able to negotiate about their fertility (IV). Knowledge about reproductive life could prepare young women better for the future life and give them more control of their fertility. Innovative interventions targeting women need to challenge current societal norms of womanhood to promote the upbringing of confident and knowledgeable young women

Galiellalactone Inhibits Stem Cell-Like ALDH-Positive Prostate Cancer Cells

Galiellalactone is a potent and specific inhibitor of STAT3 signaling which has been shown to possess growth inhibitory effects on prostate cancer cells expressing active STAT3. In this study we aimed to investigate the effect of galiellalactone on prostate cancer stem cell-like cells. We explored the expression of aldehyde dehydrogenase (ALDH) as a marker for cancer stem cell-like cells in different human prostate cancer cell lines and the effects of galiellalactone on ALDH expressing (ALDH+) prostate cancer cells. ALDH+ subpopulations were detected and isolated from the human prostate cancer cell lines DU145 and long-term IL-6 stimulated LNCaP cells using ALDEFLUOR® assay and flow cytometry. In contrast to ALDH− cells, ALDH+ prostate cancer cells showed cancer stem cell-like characteristics such as increased self-renewing and colony forming capacity and tumorigenicity. In addition, ALDH+ cells showed an increased expression of putative prostate cancer stem cell markers (CD44 and integrin α2β1). Furthermore, ALDH+ cells expressed phosphorylated STAT3. Galiellalactone treatment decreased the proportion of ALDH+ prostate cancer cells and induced apoptosis of ALDH+ cells. The gene expression of ALDH1A1 was downregulated in vivo in galiellalactone treated DU145 xenografts. These findings emphasize that targeting the STAT3 pathway in prostate cancer cells, including prostate cancer stem cell-like cells, is a promising therapeutic approach and that galiellalactone is an interesting compound for the development of future prostate cancer drugs

Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.