21 research outputs found
Increased Serum Concentrations of Circulating Glycocalyx Components in HELLP Syndrome Compared to Healthy Pregnancy: An Observational Study
Severe inflammation has been shown to induce a shedding of the endothelial glycocalyx (EGX). Inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), impede the thickness of the EGX. While a controlled inflammatory reaction occurs already in normal pregnancy, women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome had an exaggerated inflammatory response. This study investigates the shedding of the glycocalyx during normal pregnancy and in women with HELLP syndrome. Glycocalyx components (syndecan 1, heparan sulfate, and hyaluronic acid) were measured in serum of healthy women throughout pregnancy (4 time points, n = 26), in women with HELLP syndrome (n = 17) before delivery and in nonpregnant volunteers (n = 10). Serum concentrations of TNF-alpha and soluble TNF-alpha receptors (sTNF-Rs) were assessed once in all 3 groups. Syndecan 1 serum concentrations constantly rose throughout normal pregnancy. Immediately before delivery, a 159-fold increase was measured compared to nonpregnant controls (P < .01). Even higher amounts were observed in patients with HELLP prior to delivery (median 12 252 ng/mL) compared to healthy women matched by gestational age (median 5943 ng/mL; P < .01). Relevantly, increased serum levels of heparan sulfate, hyaluronic acid, and sTNF-Rs were only detected in patients with HELLP (P < .01). These findings suggest that considerable amounts of syndecan 1 are released into maternal blood during uncomplicated pregnancy. The HELLP syndrome is associated with an even more pronounced shedding of glycocalyx components. The maternal vasculature as well as the placenta has to be discussed as a possible origin of circulating glycocalyx components
Influence of bisphosphonate therapy on bone geometry, volumetric bone density and bone strength of femoral shaft in postmenopausal women with rheumatoid arthritis
Iminothiol/thiourea tautomeric equilibrium in thiourea lipids impacts DNA compaction by inducing a cationic nucleation for complex assembly
Costs of antibiotic resistance â separating trait effects and selective effects
Antibiotic resistance can impair bacterial growth or competitive ability in the absence of antibiotics, frequently referred to as a âcostâ of resistance. Theory and experiments emphasize the importance of such effects for the distribution of resistance in pathogenic populations. However, recent work shows that costs of resistance are highly variable depending on environmental factors such as nutrient supply and population structure, as well as genetic factors including the mechanism of resistance and genetic background. Here, we suggest that such variation can be better understood by distinguishing between the effects of resistance mechanisms on individual traits such as growth rate or yield (âtrait effectsâ) and effects on genotype frequencies over time (âselective effectsâ). We first give a brief overview of the biological basis of costs of resistance and how trait effects may translate to selective effects in different environmental conditions. We then review empirical evidence of genetic and environmental variation of both types of effects and how such variation may be understood by combining molecular microbiological information with concepts from evolution and ecology. Ultimately, disentangling different types of costs may permit the identification of interventions that maximize the cost of resistance and therefore accelerate its decline.ISSN:1752-4571ISSN:1752-456
Data from: Individual- versus group-optimality in the production of secreted bacterial compounds
How unicellular organisms optimize the production of compounds is a fundamental biological question. While it is typically thought that production is optimized at the individual-cell level, secreted compounds could also allow for optimization at the group level, leading to a division of labor where a subset of cells produces and shares the compound with everyone. Using mathematical modelling, we show that the evolution of such division of labor depends on the cost function of compound production. Specifically, for any trait with saturating benefits, linear costs promote the evolution of uniform production levels across cells. Conversely, production costs that diminish with higher output levels favor the evolution of specialization â especially when compound shareability is high. When experimentally testing these predictions with pyoverdine, a secreted iron-scavenging compound produced by Pseudomonas aeruginosa, we found linear costs and, consistent with our model, detected uniform pyoverdine production levels across cells. We conclude that for shared compounds with saturating benefits, the evolution of division of labor is facilitated by a diminishing cost function. More generally, we note that shifts in the level of selection from individuals to groups do not solely require cooperation, but critically depend on mechanistic factors, including the distribution of compound synthesis costs
Individualâ versus groupâoptimality in the production of secreted bacterial compounds
How unicellular organisms optimize the production of compounds is a fundamental biological question. While it is typically thought that production is optimized at the individual-cell level, secreted compounds could also allow for optimization at the group level, leading to a division of labor where a subset of cells produces and shares the compound with everyone. Using mathematical modelling, we show that the evolution of such division of labor depends on the cost function of compound production. Specifically, for any trait with saturating benefits, linear costs promote the evolution of uniform production levels across cells. Conversely, production costs that diminish with higher output levels favor the evolution of specialization â especially when compound shareability is high. When experimentally testing these predictions with pyoverdine, a secreted iron-scavenging compound produced by Pseudomonas aeruginosa, we found linear costs and, consistent with our model, detected uniform pyoverdine production levels across cells. We conclude that for shared compounds with saturating benefits, the evolution of division of labor is facilitated by a diminishing cost function. More generally, we note that shifts in the level of selection from individuals to groups do not solely require cooperation, but critically depend on mechanistic factors, including the distribution of compound synthesis costs