Microorganisms are found in diverse communities whose structure and function are determined by interspecific interactions. Just as single species seldom exist in isolation, communities as a whole are also constantly challenged and affected by external species. Though much work has been done on characterizing how individual species affect each other through pairwise interactions, the joint effects of multiple species on a single (focal) species, remain under explored. As such, it is still unclear how single species effects combine to a community-level effect on a species of interest. To explore this relationship, we assayed thousands of communities of two, three, and four bacterial species, measuring the effect of single, pairs of, and trios of 61 affecting species on six different focal species. We found that when multiple species each have a negative effect on a focal species, their joint effect is typically not given by the sum of the effects of individual affecting species. Rather, they are dominated by the strongest individual-species effect. Therefore, while joint effects of multiple species are often non-additive, they can still be derived from the effects of individual species, making it plausible to map complex interaction networks based on pairwise measurements. This finding is important for understanding the fate of species introduced into an occupied environment, and is relevant for applications in medicine and agriculture, such as probiotics and biocontrol agents, as well as for ecological questions surrounding migrating and invasive species.
Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR‐4734 in restricting ATF4 and IRE1‐mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress‐associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR‐4734 was found to restrict the expression of the transcriptional activator NF‐kappa‐B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR‐4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR‐4734, underscoring the importance of this direct targeting. As the effects of miR‐4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress‐induced pathologies.
Microorganisms are found in diverse communities whose structure and function are determined by interspecific interactions. Just as single species seldom exist in isolation, communities as a whole are also constantly challenged and affected by external species. Though much work has been done on characterizing how individual species affect each other through pairwise interactions, the joint effects of multiple species on a single (focal) species, remain under explored. As such, it is still unclear how these single species effects combine to a community-level effect on a species of interest. To explore this relationship, we assayed over 14,000 communities of two, three, and four bacterial species, measuring the effect of single, pairs of, and trios of 61 affecting species on six different focal species. Our results demonstrate that joint effects of multiple species on a focal species are not given by the sum of the effects of individual affecting species. Rather, they are dominated by the strongest individual-species effect. Therefore, while joint effects of multiple species are highly non-additive, they can still be derived from the effects of individual species, making it plausible to map complex interaction networks based on pairwise measurements. This finding is important for understanding the fate of species introduced into an occupied environment, and is relevant for applications in medicine and agriculture, such as probiotics and biocontrol agents, as well as for ecological questions surrounding migrating and invasive species.
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