Enrichment and association of lead and bacteria at particulate surfaces in a salt-marsh surface layer

The particle-laden surface layer (~ 150-370 µm) and subsurface waters of a South San Francisco Bay salt marsh were sampled over two tidal cycles and analyzed for particle numbers and particulate-associated and total concentrations of lead and bacteria…

Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

© 2017 The Author(s). Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-ΰ B translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-ΰ B signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-k B translocation into the nucleus that resulted in high NF-k B transcription activity. The overall magnitude of NF-k B transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-k B translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-k B transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-k B transcription factor

Barriers for progress in salt reduction in the general population. An international study

Salt reduction is important for reducing hypertension and the risk of cardiovascular events, nevertheless worldwide salt intakes are above recommendations. Consequently strategies to reduce intake are required, however these require an understanding of salt intake behaviours to be effective. As limited information is available on this, an international study was conducted to derive knowledge on salt intake and associated behaviours in the general population. An online cohort was recruited consisting of a representative sample from Germany, Austria, United States of America, Hungary, India, China, South Africa, and Brazil (n=6987; aged 18-65. years; age and gender stratified). Participants completed a comprehensive web-based questionnaire on salt intake and associated behaviours. While salt reduction was seen to be healthy and important, over one third of participants were not interested in salt reduction and the majority were unaware of recommendations. Salt intake was largely underestimated and people were unaware of the main dietary sources of salt. Participants saw themselves as mainly responsible for their salt intake, but also acknowledged the roles of others. Additionally, they wanted to learn more about why salt was bad for health and what the main sources in the diet were. As such, strategies to reduce salt intake must raise interest in engaging in salt reduction through improving understanding of intake levels and dietary sources of salt. Moreover, while some aspects of salt reduction can be globally implemented, local tailoring is required to match level of interest in salt reduction. These findings provide unique insights into issues surrounding salt reduction and should be used to develop effective salt reduction strategies and/or policies. © 2013 The Authors

Ethanol exposure perturbs sea urchin development and disrupts developmental timing

Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal alcohol syndrome (FAS). Our results show that sea urchin embryos treated with ethanol similarly show broad skeletal patterning defects, potentially analogous to the defects associated with FAS. The sea urchin larval skeleton is a simple patterning system that involves only two cell types: the primary mesenchymal cells (PMCs) that secrete the calcium carbonate skeleton and the ectodermal cells that provide migratory, positional, and differentiation cues for the PMCs. Perturbations in RA biosynthesis and Hh signaling pathways are thought to be causal for the FAS phenotype in vertebrates. Surprisingly, our results indicate that these pathways are not functionally relevant for the teratogenic effects of ethanol in developing sea urchins. We found that developmental morphology as well as the expression of ectodermal and PMC genes was delayed by ethanol exposure. Temporal transcriptome analysis revealed significant impacts of ethanol on signaling and metabolic gene expression, and a disruption in the timing of GRN gene expression that includes both delayed and precocious gene expression throughout the specification network. We conclude that the skeletal patterning perturbations in ethanol-treated embryos likely arise from a loss of temporal synchrony within and between the instructive and responsive tissues.IOS-1656752 - National Science Foundation; National Science FoundationFirst author draf

Limited role of spatial selfstructuring in emergent trade-offs during pathogen evolution

Pathogen transmission and virulence are main evolutionary variables broadly assumed to be linked through trade-offs. In well-mixed populations, these trade-offs are often ascribed to physiological restrictions, while populations with spatial self-structuring might evolve emergent trade-offs. Here, we reexamine a spatially-explicit, SIR model of the latter kind proposed by Ballegooijen and Boerlijst with the aim of characterising the mechanisms causing the emergence of the trade-off and its structural robustness. Using invadability criteria, we establish the conditions under which an evolutionary feedback between transmission and virulence mediated by pattern formation can poise the system to a critical boundary separating a disordered state (without emergent trade-off) from a self-structured phase (where the trade-off emerges), and analytically calculate the functional shape of the boundary in a certain approximation. Beyond evolutionary parameters, the success of an invasion depends on the size and spatial structure of the invading and invaded populations. Spatial self-structuring is often destroyed when hosts are mobile, changing the evolutionary dynamics to those of a well-mixed population. In a metapopulation scenario, the systematic extinction of the pathogen in the disordered phase may counteract the disruptive effect of host mobility, favour pattern formation and therefore recover the emergent trade-off.This work has been supported by the Spanish Ministerio de Economía, Industria y Competitividad and FEDER funds of the EU through grants ViralESS (FIS2014-57686-P and FIS2017-84256-P). The internship of VB was financed by the Severo Ochoa Centers of Excellence Program (SEV-2013-0347)

ICAT: a novel algorithm to robustly identify cell states following perturbations in single cell transcriptomes

IOS-1656752 - National Science FoundationFirst author draf

PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients

After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations

Systemic properties of metabolic networks lead to an epistasis-based model for heterosis

The genetic and molecular approaches to heterosis usually do not rely on any model of the genotype–phenotype relationship. From the generalization of Kacser and Burns’ biochemical model for dominance and epistasis to networks with several variable enzymes, we hypothesized that metabolic heterosis could be observed because the response of the flux towards enzyme activities and/or concentrations follows a multi-dimensional hyperbolic-like relationship. To corroborate this, we used the values of systemic parameters accounting for the kinetic behaviour of four enzymes of the upstream part of glycolysis, and simulated genetic variability by varying in silico enzyme concentrations. Then we “crossed” virtual parents to get 1,000 hybrids, and showed that best-parent heterosis was frequently observed. The decomposition of the flux value into genetic effects, with the help of a novel multilocus epistasis index, revealed that antagonistic additive-by-additive epistasis effects play the major role in this framework of the genotype–phenotype relationship. This result is consistent with various observations in quantitative and evolutionary genetics, and provides a model unifying the genetic effects underlying heterosis