We investigated the spatial variability of picocyanobacterial community structure across the Costa Rica Dome (CRD), an offshore upwelling system characterized by high seasonal abundance of Synechococcus spp. We constructed clone libraries of the rpoC1 gene to survey picocyanobacterial diversity and developed specific real-time quantitative polymerase chain reaction assays to assess the distribution of genetically distinct Synechococcus (SYN) and Prochlorococcus (PRO) populations across vertical and horizontal physicochemical gradients. Flow cytometry data showed that cell abundances for both SYN and PRO were highest near the dome center. Phylogenetic analysis of rpoC1 sequences revealed a remarkably high and distinctive picocyanobacterial diversity (FLU1-3, CRD1, Clade II, XV, XVI) that included "novel" SYN and PRO genotypes. Furthermore, genetically different populations exhibited vertical and horizontal spatial partitioning. Abundances of distinct SYN genotypes peaked at subsequent depth horizons, leading to a fine vertical structure with at least three populations stacked within the upper 30-40 m at the dome. Clade II and FLU1A peaked in surface waters, while maximum concentrations of CRD1, FLU1B, and Clade XVI occurred in the upper and lower thermocline, respectively. Horizontally, Clade II abundance in surface waters remained high across the entire region, while SYN genotypes CRD1 and FLU1A increased with shoaling of the thermo- and nutricline toward the center of the dome to become the dominant genotypes of the SYN assemblage in the dome. Below the mixed layer, Clade XVI and PRO genotype FLU2, virtually absent outside the dome, became abundant components of the picocyanobacterial assemblage. Despite their phylogenetic relatedness, FLU1A and FLU1B subclades followed different distributional patterns, suggesting ecological significance of the microdiversity within the clade. The unprecedented fine vertical structure demonstrated for SYN genotypes is driven by sharp physicochemical gradients (e.g., density, nutrient, oxygen, and trace metals) created by the dome and the presence of a shallow oxycline that enhances habitat diversification. © 2014, by the Association for the Sciences of Limnology and Oceanography, Inc.

Columbamides are chlorinated acyl amide natural products, several of which exhibit cannabinomimetic activity. These compounds were originally discovered from a culture of the filamentous marine cyanobacterium Moorena bouillonii PNG5-198 collected from the coastal waters of Papua New Guinea. The columbamide biosynthetic gene cluster (BGC) had been identified using bioinformatics, but not confirmed by experimental evidence. Here, we report the heterologous expression in Anabaena (Nostoc) PCC 7120 of the 28.5 kb BGC that encodes for columbamide biosynthesis. The production of columbamides in Anabaena is investigated under several different culture conditions, and several new columbamide analogs are identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR). In addition to previously characterized columbamides A, B, and C, new columbamides I-M are produced in these experiments, and the structure of the most abundant monochlorinated analog, columbamide K (11), is fully characterized. The other new columbamide analogs are produced in only small quantities, and structures are proposed based on high-resolution-MS, MS/MS, and ¹H NMR data. Overexpression of the pathway's predicted halogenases resulted in increased productions of di- and trichlorinated compounds. The most significant change in production of columbamides in Anabaena is correlated with the concentration of NaCl in the medium.

Covering: up to 2016Humans are walking microbial ecosystems, each harboring a complex microbiome with the genetic potential to produce a vast array of natural products. Recent sequencing data suggest that our microbial inhabitants are critical for maintaining overall health. Shifts in microbial communities have been correlated to a number of diseases including infections, inflammation, cancer, and neurological disorders. Some of these clinically and diagnostically relevant phenotypes are a result of the presence of small molecules, yet we know remarkably little about their contributions to the health of individuals. Here, we review microbe-derived natural products as mediators of human disease.

UNLABELLED: Gastrointestinal diseases are the most frequently reported clinical problems in captive common marmosets (Callithrix jacchus), often affecting the health and welfare of the animal and ultimately their use as a research subject. The microbiome has been shown to be intimately connected to diet and gastrointestinal health. Here, we use shotgun metagenomics and untargeted metabolomics in fecal samples of common marmosets collected before, during, and after a dietary transition from a biscuit to a gel diet. The overall health of marmosets, measured as weight recovery and reproductive outcome, improved after the diet transition. Moreover, each marmoset pair had significant shifts in the microbiome and metabolome after the diet transition. In general, we saw a decrease in Escherichia coli and Prevotella species and an increase in Bifidobacterium species. Untargeted metabolic profiles indicated that polyamine levels, specifically cadaverine and putrescine, were high after diet transition, suggesting either an increase in excretion or a decrease in intestinal reabsorption at the intestinal level. In conclusion, our data suggest that Bifidobacterium species could potentially be useful as probiotic supplements to the laboratory marmoset diet. Future studies with a larger sample size will be beneficial to show that this is consistent with the diet change. IMPORTANCE: Appropriate diet and health of the common marmoset in captivity are essential both for the welfare of the animal and to improve experimental outcomes. Our study shows that a gel diet compared to a biscuit diet improves the health of a marmoset colony, is linked to increases in Bifidobacterium species, and increases the removal of molecules associated with disease. The diet transition had an influence on the molecular changes at both the pair and time point group levels, but only at the pair level for the microbial changes. It appears to be more important which genes and functions present changed rather than specific microbes. Further studies are needed to identify specific components that should be considered when choosing an appropriate diet and additional supplementary foods, as well as to validate the benefits of providing probiotics. Probiotics containing Bifidobacterium species appear to be useful as probiotic supplements to the laboratory marmoset diet, but additional work is needed to validate these findings.

The dimeric 44-residue E5 protein of bovine papillomavirus is the smallest known naturally occurring oncoprotein. This transmembrane protein binds to the transmembrane domain (TMD) of the platelet-derived growth factor β receptor (PDGFβR), causing dimerization and activation of the receptor. Here, we use Rosetta membrane modeling and all-atom molecular dynamics simulations in a membrane environment to develop a chemically detailed model of the E5 protein/PDGFβR complex. In this model, an active dimer of the PDGFβR TMD is sandwiched between two dimers of the E5 protein. Biochemical experiments showed that the major PDGFβR TMD complex in mouse cells contains two E5 dimers and that binding the PDGFβR TMD to the E5 protein is necessary and sufficient to recruit both E5 dimers into the complex. These results demonstrate how E5 binding induces receptor dimerization and define a molecular mechanism of receptor activation based on specific interactions between TMDs.

The chemistry of indoor surfaces and the role of microbes in shaping and responding to that chemistry are largely unexplored. We found that, over 1 month, people's presence and activities profoundly reshaped the chemistry of a house. Molecules associated with eating/cooking, bathroom use, and personal care were found throughout the entire house, while molecules associated with medications, outdoor biocides, and microbially derived compounds were distributed in a location-dependent manner. The house and its microbial occupants, in turn, also introduced chemical transformations such as oxidation and transformations of foodborne molecules. The awareness of and the ability to observe the molecular changes introduced by people should influence future building designs.

Many small parasitoid wasps have a black head, an orange mesosoma and a black metasoma (BOB color pattern), which is usually present in both sexes. A likely function of this widespread pattern is aposematic (warning) coloration, but this has never been investigated. To test this hypothesis, we presented spider predators (Lyssomanes jemineus), both field-captured and bred in captivity from eggs, to four wasp genera (Baryconus, Chromoteleia, Macroteleia and Scelio), each genus being represented by a BOB morphospecies and black morphospecies. We also used false prey, consisting of lures made of painted rice grains. Behavioral responses were analyzed with respect to presence or absence of the BOB pattern. In order to better understand the results obtained, two additional studies were performed. First, the reflection spectrum of the cuticle of the wasp and a theoretical visual sensibility of the spider were used to calculate a parameter we called "absorption contrast" that allows comparing the perception contrast between black and orange in each wasp genus as viewed by the spider. Second, acute toxicity trials with the water flea, Daphnia magna, were performed to determine toxicity differences between BOB and non-BOB wasps. At least some of the results suggest that the BOB color pattern may possibly play an aposematic role.

The host-microbiome associations occurring on the skin of vertebrates significantly influence hosts health. However, the factors mediating their interactions remain largely unknown. Herein, we used integrated technical and ecological frameworks to investigate the skin metabolites sustaining a beneficial symbiosis between tree frogs and bacteria. We characterize macrocyclic acylcarnitines as the major metabolites secreted by the frogs skin and trace their origin to an enzymatic unbalance of carnitine palmitoyltransferases. We found that these compounds colocalize with bacteria on the skin surface and are mostly represented by members of the Pseudomonas community. We showed that Pseudomonas sp. MPFS isolated from frogs skin can exploit acylcarnitines as its sole carbon and nitrogen source, and this metabolic capability is widespread in Pseudomonas. We summarize frogs multiple mechanisms to filter environmental bacteria and highlight that acylcarnitines likely evolved for another function but were co-opted to provide nutritional benefits to the symbionts.

White teeth can give confidence and tend to be associated with a healthier lifestyle in modern society. Therefore, tooth-bleaching strategies have been developed, including the use of hydrogen peroxide. Recently, peroxymonosulfate has been introduced as an alternative bleaching method to hydrogen peroxide. Although both chemicals are oxidizing agents, their effects on the molecular composition of the stained teeth are yet unknown. In this study, the molecular profiles of teeth bleached with hydrogen peroxide and peroxymonosulfate were compared using Liquid Chromatography-Tandem Mass Spectrometry. Statistical analyses were used to assess the samples. In addition, reference spectral libraries and in silico tools were used to perform metabolite annotation. Overall, principal component analysis showed a strong separation between control and hydrogen peroxide and peroxymonosulfate samples (p < 0.001). The analysis of molecular changes revealed amino acids and dipeptides in stained teeth samples after hydrogen peroxide and peroxymonosulfate treatments. Noteworthy, the two bleaching methods led to distinct molecular profiles. For example, diterpenoids were more prevalent after peroxymonosulfate treatment, while a greater abundance of alkaloids was detected after hydrogen peroxide treatment. Whereas non-bleached samples (controls) showed mainly lipids. Therefore, this study shows how two different tooth-whitening peroxides could affect the molecular profiles of human teeth.