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Mounting evidence supports the potential of dietary bioactives to reduce chronic disease risk. N-trans-caffeoyltyramine (NCT) and N-trans-feruloyltyramine (NFT) have been hypothesized to drive regulation of gut permeability, but these components have not yet been studied in the context of the human gut microbiome. This work examined whether purified NCT and NFT, or a hemp hull product containing NCT and NFT (Brightseed® Bio Gut Fiber™), can impact the gut microbiome using an in vitro fermentation assay. Representative human gut microbiomes were treated with Bio Gut Fiber™ or NCT and NFT and compared to starch and methylcellulose, as controls, in vitro. Stronger changes were exerted by Bio Gut Fiber™, NCT, and NFT. Communities treated with Bio Gut Fiber™ saw increased productivity and diversity. We found a dose-dependent effect of NCT and NFT on microbial communities. Here, we describe novel potential for hemp-derived bioactives to shape the gut microbiome.

Campylobacter jejuni is a common foodborne pathogen found in poultry that can cause severe life-threatening illnesses in humans. It is important to detect this pathogen in food to manage foodborne outbreaks. This study reports a novel impedimetric phage protein-based biosensor to detect C. jejuni NCTC 11168 at 100 CFU/mL concentrations using a genetically engineered receptor-binding phage protein, FlaGrab, as a bioreceptor. The electrochemical impedance spectroscopy (EIS) technique was employed to measure changes in resistance upon interaction with C. jejuni. The sensitivity of the phage protein-immobilized electrode was assessed using the various concentrations of C. jejuni NCTC 11168 ranging from 102–109 colony forming units (CFU)/mL). The change transfer resistance of the biosensor increased with increasing numbers of C. jejuni NCTC 11168 cells. The detection limit was determined to be approximately 103 CFU/mL in the buffer and 102 CFU/mL in the ex vivo samples. Salmonella enterica subsp. enterica serotype Typhimurium-291RH and Listeria monocytogenes Scott A were used as nontarget bacterial cells to assess the specificity of the developed biosensor. Results showed that the developed biosensor was highly specific toward the target C. jejuni NCTC 11168, as no signal was observed for the nontarget bacterial cells.

Abstract Regulatory guidelines for tissue engineered products require stringent characterization during production and necessitate the development of novel, non-destructive methods to quantify key functional parameters for clinical translation. Traditional assessments of engineered tissues are destructive, expensive, and time consuming. Here, we introduce a non-destructive, inexpensive, and rapid sampling and analysis system that can continuously monitor the mechanical, biochemical, and structural properties of a single sample over extended periods of time. The label-free system combines the imaging modalities of fluorescent lifetime imaging and ultrasound backscatter microscopy through a fiber-based interface for sterile monitoring of tissue quality. We tested the multimodal system using tissue engineered articular cartilage as an experimental model. We identified strong correlations between optical and destructive testing. Combining FLIm and UBM results, we created a novel statistical model of tissue homogeneity that can be applied to tissue engineered constructs prior to implantation. Continuous monitoring of engineered tissues with this non-destructive system has the potential for in-process monitoring of tissue engineered products, reducing costs and improving quality controls in research, manufacturing, and clinical applications.

Sustainable aquaculture practices can help meet the increasing human demand for seafood, while easing pressures on natural fish populations. Studies aimed at increasing fish production in aquaculture have included supplementary dietary probiotics that often promote general health and enhanced growth rates by altering the microbiome of the host. Steelhead trout (Oncorhynchus mykiss) is anadromous, like salmon, and it is a subspecies of rainbow trout capable of rapid growth, making it an attractive fish to the aquaculture industry. In this study, the impact of feeding a Bacillus subtilis probiotic on the bacterial microbiome of steelhead trout was examined temporally across several stages of animal development, from eggs (day -19) through 184 days after hatching, in relation to physiological measures. Diets included: commercial feed only as a control (A), continually-fed probiotic top-coated on commercial feed (B), commercial then switch to probiotic feed (C), or probiotic then switch to commercial feed (D). Validation of probiotic concentrations on feed and in fish tissues was performed using CFU/g and qPCR, respectively. Fish growth was measured and samples for intestinal microbiome analyses were collected at multiple timepoints during fish development. Fish fed diet D yielded higher weights than the other three diets, with little impact on other biometric parameters. However, bacterial microbiome analysis indicated an increasing trend of overall alpha diversity from the egg stage to day 29 for fish fed the various diets with diet D having the highest diversity. Fish fed diets A and D maintained a high alpha diversity beyond day 29 in contrast to a decreased trend for fish still being fed probiotics in diets B and C. The fish fed diets B and C harbored a significantly higher relative abundance of Bacillus sp. in their total microbiomes (feces + mucosa). Interestingly, the mucosal-only microbiome indicated little variation between the four groups of fish. Feeding the probiotic earlier in development, during the hatchery phase, to influence bacterial microbiome composition in the intestine (rather than later after the microbiome has been established) appears to be a more effective aquaculture practice by enhancing microbiome diversity while enabling higher fish yields.

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

Antimicrobial resistance is an ancient bacterial defense mechanism that has rapidly spread due to the frequent use of antibiotics for disease treatment and livestock growth promotion. We are becoming increasingly aware that pathogens, such as members of the genus Acinetobacter, are precipitously evolving drug resistances through multiple mechanisms, including the acquisition of antibiotic resistance genes. In this study, we isolated three multidrug resistant Acinetobacter species from birds on a free-range farm. Acinetobacter radioresistens, Acinetobacter lwoffii, and Acinetobacter johnsonii were isolated from hens, turkeys and ducks and were resistant to 14 clinically relevant antibiotics, including several listed by the World Health Organization as essential medicines. Co-culturing any of the three Acinetobacter species with Acinetobacter baumannii resulted in contact-dependent release of intact resistance determinants. We also isolated several lytic bacteriophages and selected two of these phages to be included in this study based on differences in plaquing characteristics, nucleic acid content and viral morphology. Both phages released host DNA, including antibiotic resistance genes during cell lysis and we demonstrated that these resistance determinants were transferable to a naïve strain of Escherichia coli. This study demonstrates that contact-dependent competition between bacterial species can readily contribute to DNA release into the environment, including antibiotic resistance determinants. We also highlight that the constant lysis and turnover of bacterial populations during the natural lifecycle of a lytic bacteriophage is an underappreciated mechanism for the liberation of DNA and subsequent genetic exchange.

Twelve next generation emission measurement (NGEM) technologies completed single-blind testing at the Methane Emissions Technology Evaluation Center in 2018. This is the first series of tests to evaluate a wide variety of NGEM solutions including handheld, mobile, and continuous monitoring methods using comparable, repeatable protocols. Results assess performance of detection, localization and quantification, albeit with limited statistical significance due to a low number of tests. Overall, a higher detection rate is observed for handheld and mobile solutions than for continuous monitoring solutions. Compared to when a single emission source is present, a decline in detection rate is observed across all methods when multiple, steady emission sources are present. Localization by handheld and mobile solutions is more accurate than continuous monitoring solutions. These results support the common perception that detections by continuous monitoring systems will need to be confirmed and pinpointed by a follow-up inspection. Finally, this and other controlled release experiments, have been performed across a limited range of environmental conditions. To develop robust probability of detection curves needed for demonstrating emission reduction potential of leak detection and repair programs, new protocols are needed to evaluate methods across a wide range of metrological conditions and emission scenarios in a cost-effective manner.

We describe the utility of false rings in Taxodium distichum (i.e. baldcypress) as a proxy for hydroclimatic extreme events in three different river basins (Pascagoula, Mobile, and Choctawhatchee) that discharge into the northern Gulf of Mexico. False rings occur as a result of a change in the environmental limiting resource for tree stem growth, and in T. distichum , false ring production is usually a result of increases in mid-growing season water availability. Our results show that false ring occurrence (from 1931 to 2018) is similar across sites but occur in different years, suggesting that false ring production is indicative of tree response to its local environment. False ring production in T. distichum has previously been correlated with summer streamflow, the season when tropical cyclone precipitation (TCP) is highest. To assess a stand-wide response, we define high false ring (HFR) years as all years when $\geqslant$ 20% of trees produced a false ring. We show total TCP in July is the best predictor for HFR years in T. distichum , and false ring production in smaller river basins captures local TCP better than larger river basins. Additionally, HFR years coincide with summers of anomalously high precipitation, anomalously low temperatures, and a positive phase of the North Atlantic Oscillation. 77% of HFR years occur in seasons when there is heavy tropical cyclone activity near sample sites, building a foundation to use false ring records as robust TCP proxies with hydroclimate reconstruction potential.

Campylobacter jejuni is a Gram-negative foodborne pathogen that causes diarrheal disease and is associated with severe post-infectious sequelae. Bacteriophages (phages) are a possible means of reducing Campylobacter colonization in poultry to prevent downstream human infections. However, the factors influencing phage-host interactions must be better understood before this strategy can be predictably employed. Most studies have focused on Campylobacter phage binding to the host surface, with all phages classified as either capsule- or flagella-specific. Here we describe the characterization of a C. jejuni phage that requires functional flagellar glycosylation and motor genes for infection, without needing the flagella for adsorption to the cell surface. Through phage infectivity studies of targeted C. jejuni mutants, transcriptomic analysis of phage-resistant mutants, and genotypic and phenotypic analysis of a spontaneous phage variant capable of simultaneously overcoming flagellar gene dependence and sensitivity to oxidative stress, we have uncovered a link between oxidative stress, flagellar motility, and phage infectivity. Taken together, our results underscore the importance of understanding phage-host interactions beyond the cell surface and point to host oxidative stress state as an important and underappreciated consideration for future phage-host interaction studies.

Bacteriophages (phages) are predicted to be the most ubiquitous biological entity on earth, and yet, there are still vast knowledge gaps in our understanding of phage diversity and phage–host interactions. Approximately one hundred Acinetobacter-infecting DNA viruses have been identified, and in this report, we describe eight more. We isolated two typical dsDNA lytic podoviruses (CAP1–2), five unique dsRNA lytic cystoviruses (CAP3–7), and one dsDNA lysogenic siphovirus (SLAP1), all capable of infecting the multidrug resistant isolate Acinetobacter radioresistens LH6. Using transmission electron microscopy, bacterial mutagenesis, phage infectivity assays, carbohydrate staining, mass-spectrometry, genomic sequencing, and comparative studies, we further characterized these phages. Mutation of the LH6 initiating glycosyltransferase homolog, PglC, necessary for both O-linked glycoprotein and capsular polysaccharide (CPS) biosynthesis, prevented infection by the lytic podovirus CAP1, while mutation of the pilin protein, PilA, prevented infection by CAP3, representing the lytic cystoviruses. Genome sequencing of the three dsRNA segments of the isolated cystoviruses revealed low levels of homology, but conserved synteny with the only other reported cystoviruses that infect Pseudomonas species. In Pseudomonas, the cystoviruses are known to be enveloped phages surrounding their capsids with the inner membrane from the infected host. To characterize any membrane-associated glycoconjugates in the CAP3 cystovirus, carbohydrate staining was used to identify a low molecular weight lipid-linked glycoconjugate subsequently identified by mutagenesis and mass-spectrometry as bacterial lipooligosaccharide. Together, this study demonstrates the isolation of new Acinetobacter-infecting phages and the determination of their cell receptors. Further, we describe the genomes of a new genus of Cystoviruses and perform an initial characterization of membrane-associated glycoconjugates.

Despite growing in wet lowland and riparian settings, Taxodium distichum (L.) Rich. (bald cypress) has a strong response to hydroclimate variability, and tree ring chronologies derived from bald cypress have been used extensively to reconstruct drought, precipitation and streamflow. Previous studies have also demonstrated that false rings in bald cypress appear to be the result of variations in water availability during the growing season. In this study 28 trees from two sites located adjacent to the Choctawhatchee River in Northwestern Florida, USA were used to develop a false ring record extending from 1881 to 2014. Twenty false ring events were recorded during the available instrumental era (1931–2014). This record was compared with daily and monthly streamflow data from a nearby gage. All 20 of the false-ring events recorded during the instrumental period occurred during years in which greatly increased streamflow occurred late in the growing season. Many of these wet events appear to be the result of rainfall resulting from landfalling tropical cyclones. We also found that the intra-annual position of false rings within growth rings reflects streamflow variability and combining the false-ring record with tree ring width chronologies improves the estimation of overall summer streamflow by 14%. Future work using these and other quantitative approaches for the identification and measurement of false ring variables in tree rings may improve tree-ring reconstructions of streamflow and potentially the record of tropical cyclone rainfall events.

Methane (CH4) emission rates from a sample of natural gas facilities across industry sectors were quantified using the dual tracer flux ratio methodology. Measurements were conducted in study areas within the Fayetteville shale play, Arkansas (FV, Sept–Oct 2015, 53 facilities), and the Denver-Julesburg basin, Colorado, (DJ, Nov 2014, 21 facilities). Distributions of methane emission rates at facilities by type are computed and statistically compared with results that cover broader geographic regions in the US (Allen et al., 2013, Mitchell et al., 2015). DJ gathering station emission rates (kg CH4 hr–1) are lower, while FV gathering and production sites are statistically indistinguishable as compared to these multi-basin results. However, FV gathering station throughput-normalized emissions are statistically lower than multi-basin results (0.19% vs. 0.44%). This implies that the FV gathering sector is emitting less per unit of gas throughput than would be expected from the multi-basin distribution alone. The most common emission rate (i.e. mode of the distribution) for facilities in this study is 40 kg CH4 hr–1 for FV gathering stations, 1.0 kg CH4 hr–1 for FV production pads, and 11 kg CH4 hr–1 for DJ gathering stations. The importance of study design is discussed, including the benefits of site access and data sharing with industry and of a scientist dedicated to measurement coordination and site choice under evolving wind conditions.

Coordinated dual-tracer, aircraft-based, and direct component-level measurements were made at midstream natural gas gathering and boosting stations in the Fayetteville shale (Arkansas, USA). On-site component-level measurements were combined with engineering estimates to generate comprehensive facility-level methane emission rate estimates (“study on-site estimates (SOE)”) comparable to tracer and aircraft measurements. Combustion slip (unburned fuel entrained in compressor engine exhaust), which was calculated based on 111 recent measurements of representative compressor engines, accounts for an estimated 75% of cumulative SOEs at gathering stations included in comparisons. Measured methane emissions from regenerator vents on glycol dehydrator units were substantially larger than predicted by modelling software; the contribution of dehydrator regenerator vents to the cumulative SOE would increase from 1% to 10% if based on direct measurements. Concurrent measurements at 14 normally-operating facilities show relative agreement between tracer and SOE, but indicate that tracer measurements estimate lower emissions (regression of tracer to SOE = 0.91 (95% CI = 0.83–0.99), R2 = 0.89). Tracer and SOE 95% confidence intervals overlap at 11/14 facilities. Contemporaneous measurements at six facilities suggest that aircraft measurements estimate higher emissions than SOE. Aircraft and study on-site estimate 95% confidence intervals overlap at 3/6 facilities. The average facility level emission rate (FLER) estimated by tracer measurements in this study is 17–73% higher than a prior national study by Marchese et al.

Gathering pipelines, which transport gas from well pads to downstream processing, are a sector of the natural gas supply chain for which little measured methane emissions data are available. This study performed leak detection and measurement on 96 km of gathering pipeline and the associated 56 pigging facilities and 39 block valves. The study found one underground leak accounting for 83% (4.0 kg CH4/hr) of total measured emissions. Methane emissions for the 4684 km of gathering pipeline in the study area were estimated at 402 kg CH4/hr [95 to 1065 kg CH4/hr, 95% CI], or 1% [0.2% to 2.6%] of all methane emissions measured during a prior aircraft study of the same area. Emissions estimated by this study fall within the uncertainty range of emissions estimated using emission factors from EPA’s 2015 Greenhouse Inventory and study activity estimates. While EPA’s current inventory is based upon emission factors from distribution mains measured in the 1990s, this study indicates that using emission factors from more recent distribution studies could significantly underestimate emissions from gathering pipelines. To guide broader studies of pipeline emissions, we also estimate the fraction of the pipeline length within a basin that must be measured to constrain uncertainty of pipeline emissions estimates to within 1% of total basin emissions. The study provides both substantial insight into the mix of emission sources and guidance for future gathering pipeline studies, but since measurements were made in a single basin, the results are not sufficiently representative to provide methane emission factors at the regional or national level.

Tropical cyclone (TC) rainfall amounts are compared from 1950–2017 for Houston, Texas and Miami, Florida to estimate the risk of TC rain in both cities. Following the wake of Hurricanes Harvey and Irma in 2017, concern has risen over the future of raininess in these locations. Per-event rainfall amounts are aggregated using tracks taken from HURDAT, time-of-rain gathered from National Weather Service daily weather maps, and rainfall totals taken from airport monitoring stations. Risk analysis tools include descriptive statistics, time series, and return frequencies for Houston and Miami, and spatially interpolated surfaces for Hurricanes Harvey and Irma. The season duration is longer in Miami than in Houston. The uppermost rainfall events in the distribution for Houston show a significant increase through time, suggesting the most intense rainfall events are becoming worse for Houston. The expected return frequency for a Harvey-like event (940 mm) in Houston is every 230 years, on average, and the 90th percentile rain of 286 mm is expected once every 17 years (11–29; 90% significance). The expected return frequency for an Irene-like event (261 mm—maximum for location) in Miami is every 173 years, on average, and the 90th percentile rain of 167 mm is expected once every 11 years (7–17; 90% significance). Results show a substantial difference between Houston and Miami TC rainfall climatologies similar to the differences of Hurricanes Harvey and Irma. Though emergency management must be tailored for each TC, management for inland TC rainfall may be more applicable in Houston than in Miami.

Hurricane risk characteristics are examined across the U. S. Gulf of Mexico coastline using a hexagonal tessellation. Using an extreme value model, parameters are collected representing the rate or λ (frequency), the scale or σ (range), and the shape or ξ (intensity) of the extreme wind distribution. These latent parameters and the 30-year return level are visualized across the grid. The greatest 30-year return levels are located toward the center of the Gulf of Mexico, and for inland locations, along the borders of Louisiana, Mississippi, and Alabama. Using a geographically weighted regression model, the relationship of these parameters to sea surface temperature (SST) is found to assess sensitivity to change. It is shown that as SSTs increase near the coast, the frequency of hurricanes in these grids decrease significantly. This reinforces the importance of SST in areas of likely tropical cyclogenesis in determining the number of hurricanes near the coast, along with SSTs along the lifespan of the storm, rather than simply local SST. The range of hurricane wind speeds experienced near Florida is shown to increase with increasing SSTs (insignificant), suggesting that increased temperatures may allow hurricanes to maintain their strength as they pass over the Florida peninsula. The modifiable areal unit problem is assessed using multiple grid sizes. Moran's I and the local statistic G are calculated to examine spatial autocorrelation in the parameters. This research opens up future questions regarding rapid intensification and decay close to the coast and the relationship to changing SSTs.

We report the results of an observational program to investigate the gamma-ray and optical variability properties of the vRL NLSY1 galaxies listed in the Yuan et al. sample. We have identified 17 members of the Yuan et al. sample possibly associated with gamma-ray sources based on a combination of their optical polarization and optical variability and their gamma-ray properties. Eight have previously been associated with gamma-ray sources. We find nine additional members that we predict are excellent candidates to be associated with gamma-ray sources in the future. All 17 sources have many properties in common with flat spectrum radio quasars (FSRQs), suggesting that they may, in fact, constitute a new subclass of FSRQs.

Regulatory guidelines for tissue engineered products require stringent characterization during production and necessitate the development of novel, non-destructive methods to quantify key functional parameters for clinical translation. Traditional assessments of engineered tissues are destructive, expensive, and time consuming. Here, we introduce a non-destructive, inexpensive, and rapid sampling and analysis system that can continuously monitor the mechanical, biochemical, and structural properties of a single sample over extended periods of time. The label-free system combines the imaging modalities of fluorescent lifetime imaging and ultrasound backscatter microscopy through a fiber-based interface for sterile monitoring of tissue quality. We tested the multimodal system using tissue engineered articular cartilage as an experimental model. We identified strong correlations between optical and destructive testing. Combining FLIm and UBM results, we created a novel statistical model of tissue homogeneity that can be applied to tissue engineered constructs prior to implantation. Continuous monitoring of engineered tissues with this non-destructive system has the potential for in-process monitoring of tissue engineered products, reducing costs and improving quality controls in research, manufacturing, and clinical applications.

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell-cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

There is a critical need to develop noninvasive, nondestructive methods for assessing the quality of engineered constructs prior to implantation. Currently, the composition and maturity of engineered tissues are assessed using destructive, costly, and time-consuming biochemical and mechanical analyses. The goal of this study was to use noninvasive, multimodal imaging to monitor osteogenic differentiation and matrix deposition by human mesenchymal stem/stromal cells (MSCs) during in vitro culture. MSCs were encapsulated in alginate hydrogels and cultured in osteogenic conditions for 4 weeks. Samples were evaluated using fluorescence lifetime imaging (FLIm) and ultrasound backscatter microscopy (UBM) prior to traditional biochemical and mechanical testing. Using linear regression analysis, we identified strong correlations between imaging parameters (e.g., fluorescence lifetime and acoustic attenuation coefficient) and destructive mechanical and biochemical tests to assess the maturation of osteogenically induced constructs. These data demonstrate the promise of nondestructive label-free imaging techniques to noninvasively ascertain the progression and maturity of tissue engineered bone grafts.

Microbial‐derived natural products remain a major source of structurally diverse bioactive compounds and chemical scaffolds that have the potential as new therapeutics to target drug‐resistant pathogens and cancers. In particular, genome mining has revealed the vast number of cryptic or low‐yield biosynthetic gene clusters in the genus Streptomyces. However, low natural product yields—improvements to which have been hindered by the lack of high throughput methods—have slowed the discovery and development of many potential therapeutics. Here, we describe our efforts to improve yields of landomycins—angucycline family polyketides under investigation as cancer therapeutics—by a genetically modified Streptomyces cyanogenus 136. After simplifying the extraction process from S. cyanogenus cultures, we identified a wavelength at which the major landomycin products are absorbed in culture extracts, which we used to systematically explore culture medium compositions to improve total landomycin titers. Through correlational analysis, we simplified the culture optimization process by identifying an alternative wavelength at which culture supernatants absorb yet is representative of total landomycin titers. Using the subsequently improved sample throughput, we explored landomycin production during the culturing process to further increase landomycin yield and reduce culture time. Testing the antimicrobial activity of the isolated landomycins, we report broad inhibition of Gram‐positive bacteria, inhibition of fungi by landomycinone, and broad landomycin resistance by Gram‐negative bacteria that is likely mediated by the exclusion of landomycins by the bacterial membrane. Finally, the anticancer activity of the isolated landomycins against A549 lung carcinoma cells agrees with previous reports on other cell lines that glycan chain length correlates with activity. Given the prevalence of natural products produced by Streptomyces, as well as the light‐absorbing moieties common to bioactive natural products and their metabolic precursors, our method is relevant to improving the yields of other natural products of interest. [ABSTRACT FROM AUTHOR]