Jongeren en biologisch voedsel : een onderzoek naar de biologische consument en de jongere consument in het bijzonder

Voor een studiedag van de studiekringen Biologische landbouw en consumentenstudies van Wageningen UR hebben vier studenten een onderzoek uitgevoerd naar de voorkeuren van jongeren van 15-16 jaar voor biologische voedsel. Het rapport is uitgegevendoor de wetenschapswinke

Синтез селективно-инвариантных систем с обратными моделями

Запропоновано узагальнення методу синтезу селективно-інваріантних систем управління на випадок двоканальних немінімально-фазових об'єктів. Для вирішення задачі синтезу компенсуючих регуляторів застосовані стійкі оберненні моделі

L. plantarum WCFS1 enhances Treg frequencies by activating DCs even in absence of sampling of bacteria in the Peyer Patches

Probiotics such as L. plantarum WCFS1 can modulate immune responses in healthy subjects but how this occurs is still largely unknown. Immune-sampling in the Peyer Patches has been suggested to be one of the mechanisms. Here we studied the systemic and intestinal immune effects in combination with a trafficking study through the intestine of a well-established immunomodulating probiotic, i.e. L. plantarum WCFS1. We demonstrate that not more than 2-3 bacteria were sampled and in many animals not any bacterium could be found in the PP. Despite this, L. plantarum was associated with a strong increase in infiltration of regulatory CD103+ DCs and generation of regulatory T cells in the spleen. Also, a reduced splenic T helper cell cytokine response was observed after ex vivo restimulation. L. plantarum enhanced Treg cells and attenuated the T helper 2 response in healthy mice. We demonstrate that, in healthy mice, immune sampling is a rare phenomenon and not required for immunomodulation. Also in absence of any sampling immune activation was found illustrating that host-microbe interaction on the Peyer Patches was enough to induce immunomodulation of DCs and T-cells

An in vitro model of fibrosis using crosslinked native extracellular matrix-derived hydrogels to modulate biomechanics without changing composition

Extracellular matrix (ECM) is a dynamic network of proteins, proteoglycans and glycosaminoglycans, providing structure to the tissue and biochemical and biomechanical instructions to the resident cells. In fibrosis, the composition and the organization of the ECM are altered, and these changes influence cellular behaviour. Biochemical (i. e. protein composition) and biomechanical changes in ECM take place simultaneously in vivo. Investigating these changes individually in vitro to examine their (patho)physiological effects has been difficult. In this study, we generated an in vitro model to reflect the altered mechanics of a fibrotic microenvironment through applying fibre crosslinking via ruthenium/sodium persulfate crosslinking on native lung ECM-derived hydrogels. Crosslinking of the hydrogels without changing the biochemical composition of the ECM resulted in increased stiffness and decreased viscoelastic stress relaxation. The altered stress relaxation behaviour was explained using a generalized Maxwell model. Fibre analysis of the hydrogels showed that crosslinked hydrogels had a higher percentage of matrix with a high density and a shorter average fibre length. Fibroblasts seeded on ruthenium-crosslinked lung ECM-derived hydrogels showed myofibroblastic differentiation with a loss of spindle-like morphology together with greater α-smooth muscle actin (α-SMA) expression, increased nuclear area and circularity without any decrease in the viability, compared with the fibroblasts seeded on the native lung-derived ECM hydrogels. In summary, ruthenium crosslinking of native ECM-derived hydrogels provides an exciting opportunity to alter the biomechanical properties of the ECM-derived hydrogels while maintaining the protein composition of the ECM to study the influence of mechanics during fibrotic lung diseases. STATEMENT OF SIGNIFICANCE: Fibrotic lung disease is characterized by changes in composition and excessive deposition of extracellular matrix (ECM). ECM fibre structure also changes due to crosslinking, which results in mechanical changes. Separating the changes in composition and mechanical properties has been difficult to date. In this study, we developed an in vitro model that allows alteration of the mechanical changes alone by applying fibre crosslinking in native lung ECM-derived hydrogels. Characterisations of the crosslinked hydrogels indicated the model mimicked mechanical properties of fibrotic lung tissue and reflected altered fibre organisation. This ECM-based fibrosis model provides a method to preserve the native protein composition while altering the mechanical properties providing an important tool not only for lung but also other organ fibrosis

Exposure to violence is not associated with accuracy in forecasting conflict outcomes

Exposure to harsh or unpredictable environments can impair social and cognitive functioning. However, people may also develop enhanced abilities for solving challenges relevant in those environments (‘hidden talents’). In the current study, we explored the associations between people’s ability to accurately forecast conflict outcomes and their past and current experiences with violence. To do so, we used dynamic, real-world videos with known outcomes, rather than static, artificial stimuli (e.g., vignettes) with unknown outcomes, as previous research has done. We conducted a preregistered study in the Netherlands that included a final sample of 127 participants: 63 from a community sample and 64 college students. We found no support for our core hypothesis that people who experienced more violence are more accurate in forecasting conflict outcomes. Thus, we did not find support for hidden talents, contributing to an evidence base that was already mixed and inconclusive. We did find support for our auxiliary hypothesis that college students would wear ‘rose-colored glasses’, underestimating the number of conflicts that would escalate into fights. Contrary to our other two auxiliary hypotheses, the community sample did not overestimate the number of conflicts that would escalate into fights, and people who have experienced more violence were not more likely to predict that conflicts will escalate into fights. These findings have implications for the literature on hostile attribution bias, which shows that people with more exposure to violence more likely interpret the ambiguous actions of others as hostile. Whereas this pattern is often attributed to negativity bias in people with more exposure to violence, it might also reflect rose-colored glasses on people living safer lives

Regulation of Cellular Senescence Is Independent from Profibrotic Fibroblast-Deposited ECM

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16(Ink4a) and p21(Waf1/Cip1). However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF

Differential roles for lysyl oxidase (like), family members in chronic obstructive pulmonary disease; from gene and protein expression to function:from gene and protein expression to function

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow obstruction with cigarette smoke as a key risk factor. Extracellular matrix (ECM) alterations in COPD may lead to small airway wall fibrosis. Altered collagen cross-linking, potentially mediated by the lysyl oxidase (LO) family of enzymes (LOX, LOXL1-4), orchestrates disturbed ECM homeostasis. In this study, we investigated the effects of smoking status and presence and severity of COPD on LOs gene and protein expression in the airways and the impact of LOs inhibition on airway contraction in an ex vivo mouse model. We used gene expression data from bronchial brushings, airway smooth muscle (ASM) cells in vitro and immunohistochemistry in lung tissue to assess smoke- and COPD-associated differences in LOs gene and protein expression in the small airways. We found higher LOX expression in current- compared to ex-smokers and higher LOXL1 expression in COPD compared to non-COPD patients. LOX and LOXL2 expression were upregulated in COPD ASM cells treated with cigarette smoke extract. LOXL1 and LOXL2 protein levels were higher in small airways from current- compared to non-smokers. In COPD patients, higher LOXL1 and lower LOX protein levels were observed, but no differences for LOXL2, LOXL3, and LOXL4 protein were detected in small airways. Inhibiting LOs activity increased airway contraction in murine lung slices. COPD-associated changes in LOs, in particular LOX and LOXL1, may be related to smoking and contribute to impaired airway function, providing potential novel targets for preventing or treating small airways changes in COPD

Abnormalities in reparative function of lung-derived mesenchymal stromal cells in emphysema

Mesenchymal stromal cells (MSCs) may provide crucial support in the regeneration of destructed alveolar tissue (emphysema) in COPD. We hypothesized that lung-derived MSCs (LMSCs) from emphysema patients are hampered in their repair capacity, either intrinsically or due to their interaction with the damaged micro-environment. LMSCs were isolated from lung tissue of controls and severe emphysema patients, and characterized at baseline. Additionally, LMSCs were seeded onto control and emphysematous decellularized lung tissue scaffolds and assessed for deposition of extracellular matrix (ECM). We observed no differences in surface markers, differentiation/proliferation potential and expression of ECM genes between control- and COPD-derived LMSCs. Notably, COPD-derived LMSCs displayed lower expression of FGF10 and HGF mRNA, and HGF and decorin protein. When seeded on control decellularized lung tissue scaffolds, control and COPD-derived LMSCs showed no differences in engraftment, proliferation or survival within 2 weeks, with similar ability to deposit new matrix on the scaffolds. Moreover, LMSC numbers and ability to deposit new matrix was not compromised on emphysematous scaffolds. Collectively, our data show that LMSCs from COPD patients compared to controls show less expression of FGF10 mRNA, HGF mRNA and protein and decorin protein, while other features including the mRNA expression of various ECM molecules are unaffected. Furthermore, COPD-derived LMSCs are capable of engraftment, proliferation and functioning on native lung tissue scaffolds. The damaged, emphysematous micro-environment as such does not hamper the potential of LMSCs. Thus, specific intrinsic deficiencies in growth factor production by diseased LMSCs may contribute to impaired alveolar repair in emphysema

Subanalytic sets and feedback control

AbstractThe theory of subanalytic sets is used to prove: If a real analytic control system is completely controllable, then for every point p in the state space there exists a piecewise analytic feedback control that steers every state into p