A Two-Dimensional Model of Potassium Signaling and Oscillatory Growth in a Biofilm.

Biofilms are complex communities of bacteria that exhibit a variety of collective behaviors. These behaviors improve their ability to survive in many different environments. One of these collective behaviors seen in Bacillus subtilis is the ability for starving cells to stop the growth of other cells using potassium signaling and voltage changes. This signaling produces an oscillatory growth pattern so that during periods of low growth the nutrients diffuse deeper into the biofilm and reach the nutrient-starved, interior regions of the biomass. In this paper, we develop a mathematical model to describe this oscillatory behavior, and we use this model to develop a two-dimensional simulation that reproduces many of the important features seen in the experimental data. This simulation allows us to examine the spatial patterning of the oscillatory behavior to better understand the relationships between the various regions of the biofilm. Studying the spatial components of the metabolic and voltage oscillations could allow for the development of new control techniques for biofilms with complex shapes.

Deciphering microbial interactions in synthetic human gut microbiome communities.

The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model-guided framework to predict higher-dimensional consortia from time-resolved measurements of lower-order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi-species community dynamics, as opposed to higher-order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history-dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human-associated intestinal species and illuminated design principles of microbial communities.

Hypoxic conditioned culture medium from fibroblasts grown under embryonic-like conditions supports healing following post-laser resurfacing.

OBJECTIVES: Treatment of facial skin perturbed by laser resurfacing with a novel, topical hypoxic conditioned culture medium (HCCM) product results in apparent, accelerated wound recovery time. The HCCM product is conditioned by neonatal fibroblasts under hypoxic conditions and used as the active ingredient in a formulated topical lotion. The HCCM contains significant quantities of growth factors such as vascular endothelial growth factor, keratinocyte growth factor, and interleukin-8. As these molecules are known to play an important role in normal wound healing in vivo, we conducted a pilot clinical evaluation "Proof of Concept" in which individuals, after receiving laser resurfacing, were instructed to use either active or placebo lotion on their abraded skin. METHODS: The end points used were clinical assessment of the time to complete healing, clinical and bioinstrumental mexameter measurements of erythema, and the number of days of rescue petrolatum use by patients, post-laser. RESULTS: Day 7, post-laser treatment, resulted in a greater improvement in erythema, and re-epithelization of the peri-oral and peri-ocular regions in subjects using the active lotion vs. placebo control as determined by blinded, clinical evaluation of gross photographs and bioinstrumental mexameter measurements. A statistically significant reduction in rescue petrolatum use in active lotion-treated subjects was reported. Finally, no attendant cutaneous safety concerns (e.g., irritant/allergic dermatitis) were reported with either active or placebo lotion. CONCLUSIONS: This HCCM product may have broad applications within the field of skin wound repair.