Rare and localized events stabilize microbial community composition and patterns of spatial self-organization in a fluctuating environment

Spatial self-organization is a hallmark of surface-associated microbial communities that is governed by local environmental conditions and further modified by interspecific interactions. Here, we hypothesize that spatial patterns of microbial cell-types can stabilize the composition of cross-feeding microbial communities under fluctuating environmental conditions. We tested this hypothesis by studying the growth and spatial self-organization of microbial co-cultures consisting of two metabolically interacting strains of the bacterium Pseudomonas stutzeri. We inoculated the co-cultures onto agar surfaces and allowed them to expand (i.e. range expansion) while fluctuating environmental conditions that alter the dependency between the two strains. We alternated between anoxic conditions that induce a mutualistic interaction and oxic conditions that induce a competitive interaction. We observed co-occurrence of both strains in rare and highly localized clusters (referred to as “spatial jackpot events”) that persist during environmental fluctuations. To resolve the underlying mechanisms for the emergence of spatial jackpot events, we used a mechanistic agent-based mathematical model that resolves growth and dispersal at the scale relevant to individual cells. While co-culture composition varied with the strength of the mutualistic interaction and across environmental fluctuations, the model provides insights into the formation of spatially resolved substrate landscapes with localized niches that support the co-occurrence of the two strains and secure co-culture function. This study highlights that in addition to spatial patterns that emerge in response to environmental fluctuations, localized spatial jackpot events ensure persistence of strains across dynamic conditions.Subject terms: Microbial ecology, Biofilms     

Puzzling Findings in Studying the Outcome of “Real World” Adolescent Mental Health Services: The TRAILS Study

Background

The increased use and costs of specialist child and adolescent mental health services (MHS) urge us to assess the effectiveness of these services. The aim of this paper is to compare the course of emotional and behavioural problems in adolescents with and without MHS use in a naturalistic setting.

Method and Findings

Participants are 2230 (pre)adolescents that enrolled in a prospective cohort study, the TRacking Adolescents'' Individual Lives Survey (TRAILS). Response rate was 76%, mean age at baseline 11.09 (SD 0.56), 50.8% girls. We used data from the first three assessment waves, covering a six year period. Multiple linear regression analysis, propensity score matching, and data validation were used to compare the course of emotional and behavioural problems of adolescents with and without MHS use. The association between MHS and follow-up problem score (β 0.20, SE 0.03, p-value<0.001) was not confounded by baseline severity, markers of adolescent vulnerability or resilience nor stressful life events. The propensity score matching strategy revealed that follow-up problem scores of non-MHS-users decreased while the problem scores of MHS users remained high. When taking into account future MHS (non)use, it appeared that problem scores decreased with limited MHS use, albeit not as much as without any MHS use, and that problem scores with continuous MHS use remained high. Data validation showed that using a different outcome measure, multiple assessment waves and multiple imputation of missing values did not alter the results. A limitation of the study is that, although we know what type of MHS participants used, and during which period, we lack information on the duration of the treatment.

Conclusions

The benefits of MHS are questionable. Replication studies should reveal whether a critical examination of everyday care is necessary or an artefact is responsible for these results.     

Induction of globin mRNA expression by interleukin-3 in a stem cell factor-dependent SV-40 T-antigen-immortalized multipotent hematopoietic cell line

Erythropoiesis requires the stepwise action on immature progenitors of several growth factors, including stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (Epo). Epo is required to sustain proliferation and survival of committed progenitors and might further modulate the level of expression of several erythroid genes, including globin genes. Here we report a new SCF-dependent immortalized mouse progenitor cell line (GATA-1 ts SCF) that can also grow in either Epo or IL-3 as the sole growth factor. When grown in SCF, these cells show an "open" chromatin structure of the beta-globin LCR, but do not significantly express globin. However, Epo or IL-3 induce globin expression and are required for its maintainance. This effect of IL-3 is unexpected as IL-3 was previously reported either to be unable to induce hemoglobinization, or even to antagonize it. This suggests that GATA-1 ts SCF cells may have progressed to a stage in which globin genes are already poised for expression and only require signal(s) that can be elicited by either Epo or IL-3. Through the use of inhibitors, we suggest that p38 may be one of the molecules modulating induction and maintenance of globin expression.     

Polymerization of Horseradish Peroxidase by a Laccase‐Catalyzed Tyrosine Coupling Reaction

The polymerization of proteins can create newly active and large bio‐macromolecular assemblies that exhibit unique functionalities depending on the properties of the building block proteins and the protein units in polymers. Herein, the first enzymatic polymerization of horseradish peroxidase (HRP) is reported. Recombinant HRPs fused with a tyrosine‐tag (Y‐tag) through a flexible linker at the N‐ and/or C‐termini are expressed in silkworm, Bombyx mori. Trametes sp. laccase (TL) is used to activate the tyrosine of Y‐tagged HRPs with molecular O₂ to form a tyrosyl‐free radical, which initiates the tyrosine coupling reaction between the HRP units. A covalent dityrosine linkage is also formed through a HRP‐catalyzed self‐crosslinking reaction in the presence of H₂O₂. The addition of H₂O₂ in the self‐polymerization of Y‐tagged HRPs results in lower activity of the HRP polymers, whereas TL provides site‐selectivity, mild reaction conditions and maintains the activity of the polymeric products. The cocrosslinking of Y‐tagged HRPs and HRP‐protein G (Y‐HRP‐pG) units catalyzed by TL shows a higher signal in enzyme‐linked immunosorbent assay (ELISA) than the genetically pG‐fused HRP, Y‐HRP‐pG, and its polymers. This new enzymatic polymerization of HRP promises to provide highly active and functionalized polymers for biomedical applications and diagnostics probes.