Complex Microbiome Underlying Secondary and Primary Metabolism in the Tunicate-\u3cem\u3eProchloron\u3c/em\u3e Symbiosis

The relationship between tunicates and the uncultivated cyanobacterium Prochloron didemni has long provided a model symbiosis. P. didemni is required for survival of animals such as Lissoclinum patella and also makes secondary metabolites of pharmaceutical interest. Here, we present the metagenomes, chemistry, and microbiomes of four related L. patella tunicate samples from a wide geographical range of the tropical Pacific. The remarkably similar P. didemni genomes are the most complex so far assembled from uncultivated organisms. Although P. didemni has not been stably cultivated and comprises a single strain in each sample, a complete set of metabolic genes indicates that the bacteria are likely capable of reproducing outside the host. The sequences reveal notable peculiarities of the photosynthetic apparatus and explain the basis of nutrient exchange underlying the symbiosis. P. didemni likely profoundly influences the lipid composition of the animals by synthesizing sterols and an unusual lipid with biofuel potential. In addition, L. patella also harbors a great variety of other bacterial groups that contribute nutritional and secondary metabolic products to the symbiosis. These bacteria possess an enormous genetic potential to synthesize new secondary metabolites. For example, an antitumor candidate molecule, patellazole, is not encoded in the genome of Prochloron and was linked to other bacteria from the microbiome. This study unveils the complex L. patella microbiome and its impact on primary and secondary metabolism, revealing a remarkable versatility in creating and exchanging small molecules

Variation in Tropical Reef Symbiont Metagenomes Defined by Secondary Metabolism

The complex evolution of secondary metabolism is important in biology, drug development, and synthetic biology. To examine this problem at a fine scale, we compared the genomes and chemistry of 24 strains of uncultivated cyanobacteria, Prochloron didemni, that live symbiotically with tropical ascidians and that produce natural products isolated from the animals. Although several animal species were obtained along a >5500 km transect of the Pacific Ocean, P. didemni strains are >97% identical across much of their genomes, with only a few exceptions concentrated in secondary metabolism. Secondary metabolic gene clusters were sporadically present or absent in identical genomic locations with no consistent pattern of co-occurrence. Discrete mutations were observed, leading to new chemicals that we isolated from animals. Functional cassettes encoding diverse chemicals are exchanged among a single population of symbiotic P. didemni that spans the tropical Pacific, providing the host animals with a varying arsenal of secondary metabolites

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Minimum Information about a Biosynthetic Gene cluster

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.Chemistry and Chemical Biolog

A Toolbox for Microbiome Engineering

Genetic tools to engineer a prominent member of the human gut microbiome represent initial steps toward cell-based diagnostics and therapeutics

Life in cellulose houses: symbiotic bacterial biosynthesis of ascidian drugs and drug leads

Floating offshore wind turbines may be the most practical offshore wind energy technology for deep waters. The dynamics of floating wind turbine systems is highly complicated as they are subject to irregular winds and waves, and platform motions are coupled by gyroscopic effects of the whirling blades. Computing the blade vibration is particularly challenging. The blades are highly flexible and spin around a shaft on a moving tower, introducing large deformations and irregular non-inertial frames. Blade vibration, turbine spin, and platform motion each have distinctively different frequency range, resulting in a multi-scale problem. This study is motivated by solving vibration of blades on a floating offshore wind turbine, in which the underlying theory is the dynamics of arbitrarily-shaped beams having large deformations and overall motions. Developments of two new fundamental dynamic theories are presented; a separation of displacements technique and a linearization method for small angles and small strains are proposed. A geometrically-exact nonlinear beam theory is developed based on conservation of momentum for application to arbitrarily-shaped beams having large deformations and overall motions. Coordinate transformations are used to derive the nonlinear inertial forces and moments and the nonlinear relationships between displacements and strains, enabling rigorous consideration of kinematic and geometric nonlinearities. A geometrically-exact nonlinear theory is subsequently developed for pipes conveying fluid. The derivation follows that of momentum-based beam theory: the dynamic effects of the fluid are included based on the total momentum balance of both the fluid and pipe. The fluid is viscous and is assumed to be incompressible and homogeneous. The resulting pipe theory addresses geometric and kinematic nonlinearities and inertial coupling effects. The separation of displacements technique combined with the linearization method enables nonlinear beam or pipe dynamics to be rigorously reduced to a series of piecewise-linear models. The practical value of these theoretical developments is demonstrated through numerical implementation and examples. The finite volume method is conveniently used for discretization because the underlying theories are based on a conservation law. Two piecewise-linear dynamic solvers, each for beams and pipes, are shown to capture nonlinear dynamics using linear solutions without iteration at each time-step. Momentum-based beam theory combined with multibody momentum cloud method is applied to model the fully aero-hydro-servo-elastic coupling dynamics of floating wind turbine systems. The momentum-based theory for pipes conveying fluid is demonstrated through practical application to model a top-tensioned marine riser

Small molecules from the human microbiota.

Developments in the use of genomics to guide natural product discovery and a recent emphasis on understanding the molecular mechanisms of microbiota-host interactions have converged on the discovery of small molecules from the human microbiome. Here, we review what is known about small molecules produced by the human microbiota. Numerous molecules representing each of the major metabolite classes have been found that have a variety of biological activities, including immune modulation and antibiosis. We discuss technologies that will affect how microbiota-derived molecules are discovered in the future and consider the challenges inherent in finding specific molecules that are critical for driving microbe-host and microbe-microbe interactions and understanding their biological relevance

Metabolites profiling reveals gut microbiome-mediated biotransformation of green tea polyphenols in the presence of N-nitrosamine as pro-oxidant

The gut microbiome contributes to host physiology and nutrition metabolism. The interaction between nutrition components and the gut microbiota results in thousands of metabolites that can contribute to various health and disease outcomes. In parallel, the interactions between foods and their toxicants have captured increasing interest due to their impact on human health. Taken together, investigating dietary interactions with endogenous and exogenous factors and detecting interaction biomarkers in a specific and sensitive manner is an important task. The present study sought to identify for the first time the metabolites produced during the interaction of diet-derived toxicants e.g., N-nitrosamines with green tea polyphenols, using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In addition, the metabolic products resulting from the incubation of green tea with a complex gut microbiome in the presence of N-nitrosamine were assessed in the same manner. The quinone products of (epi)catechin, quercetin, and kaempferol were identified when green tea was incubated with N-nitrosamine only; whereas, incubation of green tea with N-nitrosamine and a complex gut microbiome prevented the formation of these metabolites. This study provides a new perspective on the role of gut microbiome in protecting against potential negative interactions between food-derived toxicants and dietary polyphenols

Influence of Pickling Process on Allium cepa and Citrus limon Metabolome as Determined via Mass Spectrometry-Based Metabolomics

Brine, the historically known food additive salt solution, has been widely used as a pickling media to preserve flavor or enhance food aroma, appearance, or other qualities. The influence of pickling, using brine, on the aroma compounds and the primary and secondary metabolite profile in onion bulb Allium cepa red cv. and lemon fruit Citrus limon was evaluated using multiplex metabolomics technologies. In lemon, pickling negatively affected its key odor compound “citral”, whereas monoterpene hydrocarbons limonene and γ-terpinene increased in the pickled product. Meanwhile, in onion sulphur rearrangement products appeared upon storage, i.e., 3,5-diethyl-1,2,4-trithiolane. Profiling of the polar secondary metabolites in lemon fruit via ultra-performance liquid chromatography coupled to MS annotated 37 metabolites including 18 flavonoids, nine coumarins, five limonoids, and two organic acids. With regard to pickling impact, notable and clear separation among specimens was observed with an orthogonal projections to least squares-discriminant analysis (OPLS-DA) score plot for the lemon fruit model showing an enrichment of limonoids and organic acids and that for fresh onion bulb showing an abundance of flavonols and saponins. In general, the pickling process appeared to negatively impact the abundance of secondary metabolites in both onion and lemon, suggesting a decrease in their food health benefits