Bacterial Dysbiosis and Translocation in Psoriasis Vulgaris

CITATION: Visser, M. J. E.; Kell, D. B. & Pretorius, E. 2019. Bacterial dysbiosis and translocation in psoriasis vulgaris. Frontiers in Cellular and Infection Microbiology, 9:7. doi:10.3389/fcimb.2019.00007The original publication is available at https://www.frontiersin.org/journals/cellular-and-infection-microbiology#Psoriasis vulgaris is a chronic inflammatory skin condition, associated with both a physical and a psychological burden. Our understanding of the etiology of this disease remains incomplete. Conventionally, psoriasis has been viewed as a condition that manifests solely in the skin. However, the systemic inflammatory nature of this disease has been confirmed by the presence of a wide array of dysregulated cytokines and inflammatory markers in the serum of these patients. Both dysregulated gut and skin microbiomes have been found in association with psoriasis. An evident association also exists between inflammatory bowel disease and this condition. Regarding the skin microbiome, changes have been observed in the relative abundance of Firmicutes, Actinobacteria, and Proteobacteria. Additionally, Staphylococcus and Streptococcus spp. were detected more frequently in lesional skin. Alterations in the gut microbiome have been characterized by a decrease in the Bacteroidetes phylum and an increase in the Faecalibacterium genus. We suggest that dysbiosis of the skin and gut microbiota may contribute to psoriasis, by promoting the translocation of microbes from these sites into the bloodstream. Consistent with the Iron Dysregulation and Dormant Microbes hypothesis, these microorganisms are in a physiologically dormant state, but may be awakened periodically and shed their cell wall components, such as lipopolysaccharide and lipoteichoic acid. Both of these inflammagens may contribute significantly to maintaining a chronic inflammatory state in the host, such as is seen in individuals diagnosed with psoriasis.https://www.frontiersin.org/articles/10.3389/fcimb.2019.00007/fullPublisher’s versio

Is the association between blood pressure and cognition in the oldest-old modified by physical, vascular or brain pathology markers? The EMIF-AD 90 + Study

BACKGROUND: Prior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians’ decisions regarding the use of antihypertensives in this age group. METHODS: We included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness). RESULTS: In the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition. CONCLUSIONS: When examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

A four-dimensional {\Lambda}CDM-type cosmological model induced from higher dimensions using a kinematical constraint

A class of cosmological solutions of higher dimensional Einstein field equations with the energy-momentum tensor of a homogeneous, isotropic fluid as the source are considered with an anisotropic metric that includes the direct sum of a 3-dimensional (physical, flat) external space metric and an n-dimensional (compact, flat) internal space metric. A simple kinematical constraint is postulated that correlates the expansion rates of the external and internal spaces in terms of a real parameter {\lambda}. A specific solution for which both the external and internal spaces expand at different rates is given analytically for n=3. Assuming that the internal dimensions were at Planck length scales when the external space starts with a Big Bang (t=0), they expand only 1.49 times and stay at Planck length scales even in the present age of the universe (13.7 Gyr). The effective four dimensional universe would exhibit a behavior consistent with our current understanding of the observed universe. It would start in a stiff fluid dominated phase and evolve through radiation dominated and pressureless matter dominated phases, eventually going into a de Sitter phase at late times.Comment: 12 pages, 8 figures; matches the version published in General Relativity and Gravitatio

How Does Information Processing Speed Relate to the Attentional Blink?

Background When observers are asked to identify two targets in rapid sequence, they often suffer profound performance deficits for the second target, even when the spatial location of the targets is known. This attentional blink (AB) is usually attributed to the time required to process a previous target, implying that a link should exist between individual differences in information processing speed and the AB. Methodology/Principal Findings The present work investigated this question by examining the relationship between a rapid automatized naming task typically used to assess information-processing speed and the magnitude of the AB. The results indicated that faster processing actually resulted in a greater AB, but only when targets were presented amongst high similarity distractors. When target-distractor similarity was minimal, processing speed was unrelated to the AB. Conclusions/Significance Our findings indicate that information-processing speed is unrelated to target processing efficiency per se, but rather to individual differences in observers' ability to suppress distractors. This is consistent with evidence that individuals who are able to avoid distraction are more efficient at deploying temporal attention, but argues against a direct link between general processing speed and efficient information selection

Incidence of cancer in the area around Amsterdam Airport Schiphol in 1988–2003: a population-based ecological study

BACKGROUND: Amsterdam Airport Schiphol is a major source of complaints about aircraft noise, safety risks and concerns about long term adverse health effects, including cancer. We investigated whether residents of the area around Schiphol are at higher risk of developing cancer than the general Dutch population. METHODS: In a population-based study using the regional cancer registry, we estimated the cancer incidence during 1988–2003 in residents of the area surrounding Schiphol. We defined a study area based on aircraft noise contours and 4-digit postal code areas, since historical data on ambient air pollution were not available and recent emission data did not differ from the background urban air quality. RESULTS: In residents of the study area 13 207 cancer cases were diagnosed, which was close to the expected number, using national incidence rates as a reference (standardized incidence ratio [SIR] 1.02). We found a statistically significantly increased incidence of hematological malignancies (SIR 1.12, 95% confidence interval [CI]: 1.05, 1.19), mainly due to high rates for non-Hodgkin lymphoma (SIR 1.22, 95% CI: 1.12, 1.33) and acute lymphoblastic leukemia (SIR 1.34, 95% CI: 0.95, 1.83). The incidence of cancer of the respiratory system was statistically significantly decreased (SIR 0.94, 95% CI: 0.90, 0.99), due to the low rate in males (SIR 0.89). In the core zone of the study area, cancer incidence was slightly higher than in the remaining ring zone (rate ratio of the core zone compared to the ring zone 1.05, 95% CI 1.01, 1.10). This was caused by the higher incidence of cancer of the respiratory system, prostate and the female genital organs in the core zone in comparison to the ring zone. CONCLUSION: The overall cancer incidence in the Schiphol area was similar to the national incidence. The moderately increased risk of hematological malignancies could not be explained by higher levels of ambient air pollution in the Schiphol area. This observation warrants further research, for example in a study with focus on substances in urban ambient air pollution, as similar findings were observed in Greater Amsterdam

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

Spatial Guilds in the Serengeti Food Web Revealed by a Bayesian Group Model

Food webs, networks of feeding relationships among organisms, provide fundamental insights into mechanisms that determine ecosystem stability and persistence. Despite long-standing interest in the compartmental structure of food webs, past network analyses of food webs have been constrained by a standard definition of compartments, or modules, that requires many links within compartments and few links between them. Empirical analyses have been further limited by low-resolution data for primary producers. In this paper, we present a Bayesian computational method for identifying group structure in food webs using a flexible definition of a group that can describe both functional roles and standard compartments. The Serengeti ecosystem provides an opportunity to examine structure in a newly compiled food web that includes species-level resolution among plants, allowing us to address whether groups in the food web correspond to tightly-connected compartments or functional groups, and whether network structure reflects spatial or trophic organization, or a combination of the two. We have compiled the major mammalian and plant components of the Serengeti food web from published literature, and we infer its group structure using our method. We find that network structure corresponds to spatially distinct plant groups coupled at higher trophic levels by groups of herbivores, which are in turn coupled by carnivore groups. Thus the group structure of the Serengeti web represents a mixture of trophic guild structure and spatial patterns, in contrast to the standard compartments typically identified in ecological networks. From data consisting only of nodes and links, the group structure that emerges supports recent ideas on spatial coupling and energy channels in ecosystems that have been proposed as important for persistence.Comment: 28 pages, 6 figures (+ 3 supporting), 2 tables (+ 4 supporting

Integrating evolution into ecological modelling: accommodating phenotypic changes in agent based models.

PMCID: PMC3733718This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Evolutionary change is a characteristic of living organisms and forms one of the ways in which species adapt to changed conditions. However, most ecological models do not incorporate this ubiquitous phenomenon. We have developed a model that takes a 'phenotypic gambit' approach and focuses on changes in the frequency of phenotypes (which differ in timing of breeding and fecundity) within a population, using, as an example, seasonal breeding. Fitness per phenotype calculated as the individual's contribution to population growth on an annual basis coincide with the population dynamics per phenotype. Simplified model variants were explored to examine whether the complexity included in the model is justified. Outputs from the spatially implicit model underestimated the number of individuals across all phenotypes. When no phenotype transitions are included (i.e. offspring always inherit their parent's phenotype) numbers of all individuals are always underestimated. We conclude that by using a phenotypic gambit approach evolutionary dynamics can be incorporated into individual based models, and that all that is required is an understanding of the probability of offspring inheriting the parental phenotype

A method for estimation of elasticities in metabolic networks using steady state and dynamic metabolomics data and linlog kinetics

BACKGROUND: Dynamic modeling of metabolic reaction networks under in vivo conditions is a crucial step in order to obtain a better understanding of the (dis)functioning of living cells. So far dynamic metabolic models generally have been based on mechanistic rate equations which often contain so many parameters that their identifiability from experimental data forms a serious problem. Recently, approximative rate equations, based on the linear logarithmic (linlog) format have been proposed as a suitable alternative with fewer parameters. RESULTS: In this paper we present a method for estimation of the kinetic model parameters, which are equal to the elasticities defined in Metabolic Control Analysis, from metabolite data obtained from dynamic as well as steady state perturbations, using the linlog kinetic format. Additionally, we address the question of parameter identifiability from dynamic perturbation data in the presence of noise. The method is illustrated using metabolite data generated with a dynamic model of the glycolytic pathway of Saccharomyces cerevisiae based on mechanistic rate equations. Elasticities are estimated from the generated data, which define the complete linlog kinetic model of the glycolysis. The effect of data noise on the accuracy of the estimated elasticities is presented. Finally, identifiable subset of parameters is determined using information on the standard deviations of the estimated elasticities through Monte Carlo (MC) simulations. CONCLUSION: The parameter estimation within the linlog kinetic framework as presented here allows the determination of the elasticities directly from experimental data from typical dynamic and/or steady state experiments. These elasticities allow the reconstruction of the full kinetic model of Saccharomyces cerevisiae, and the determination of the control coefficients. MC simulations revealed that certain elasticities are potentially unidentifiable from dynamic data only. Addition of steady state perturbation of enzyme activities solved this problem