Search

Many marine algae occupy habitats that are dark, deep, or encrusted on other organisms and hence are frequently overlooked by natural product chemists. However, exploration of less-studied organisms can lead to new opportunities for drug discovery. Genetic variation at the individual, species, genus, and population levels as well as environmental influences on gene expression enable expansion of the chemical repertoire associated with a taxonomic group, enabling natural product exploration using innovative analytical methods. A nontargeted LC-MS and ¹H NMR spectroscopy-based metabolomic study of 32 collections of representatives of the calcareous red algal genus Peyssonnelia from coral reef habitats in Fiji and the Solomon Islands revealed significant correlations between natural products’ chemistry, phylogeny, and biomedically relevant biological activity. Hierarchical cluster analysis (HCA) of LC-MS data in conjunction with NMR profiling and MS/MS-based molecular networking revealed the presence of at least four distinct algal chemotypes within the genus Peyssonnelia. Two Fijian collections were prioritized for further analysis, leading to the isolation of three novel sulfated triterpene glycosides with a rearranged isomalabaricane carbon skeleton, guided by the metabolomic data. The discovery of peyssobaricanosides A–C (15–17) from two Fijian Peyssonnelia collections, but not from closely related specimens collected in the Solomon Islands that were otherwise chemically and phylogenetically very similar, alludes to population-level variation in secondary metabolite production. Our study reinforces the significance of exploring unusual ecological niches and showcases marine red algae as a chemically rich treasure trove.

Microbes produce natural products that mediate interactions with each other and with their environments, representing a potential source of antibiotics for human use. The biosynthesis of some antibiotics whose constitutive production otherwise remains low has been shown to be induced by competing microbes. Competition among macroorganism hosts may further influence the metabolic outputs of members of their microbiomes, especially near host surfaces where hosts and microbial symbionts come into close contact. At multiple field sites in Fiji, we collected matched samples of corals and algae that were freestanding or in physical contact with each other, cultivated bacteria from their surfaces, and explored growth-inhibitory activities of these bacteria against marine and human pathogens. In the course of the investigation, an interaction was discovered between two coral-associated actinomycetes in which an Agrococcus sp. interfered with the antibiotic output of a Streptomyces sp. Several diketopiperazines identified from the antibiotic-producing bacterium could not, on their own, account for the antibiotic activity indicating that other, as yet unidentified molecule(s) or molecular blends, possibly including diketopiperazines, are likely involved. This observation highlights the complex molecular dynamics at play among microbiome constituents. The mechanisms through which microbial interactions impact the biological activities of specialized metabolites deserve further attention considering the ecological and commercial importance of bacterial natural products.

The structural determination of natural products (NPs) can be arduous due to sample heterogeneity. This often demands itera-tive purification processes and characterization of complex molecules that may only be available in miniscule quantities. Microcrystal electron diffraction (microED) has recently shown promise as a method to solve crystal structures of NPs from nanogram quantities of analyte. However, its implementation in NP discovery remains hampered by sample throughput and purity requirements akin to traditional NP-discovery workflows. In the methods described herein, we leverage the resolving power of transmission electron microscopy (TEM) and the miniaturization capabilities of DNA microarray technology to address these challenges through the establishment of an NP screening platform, array electron diffraction (ArrayED). In this workflow, an array of HPLC fractions taken from crude extracts are deposited onto TEM grids in picoliter-sized droplets. This multiplexing of analytes on TEM grids enables 1200 or more unique samples to be simultaneously inserted into a TEM equipped with an autoloader. Selected area electron diffraction analysis of these microarrayed grids allows for rapid identification of crystalline metabolites. In this study, ArrayED enabled structural characterization of 14 natural products, including four novel crystal structures and two novel polymorphs, from 20 crude extracts. Moreover, we identify several chemical species that would not be detected by standard mass spectrometry (MS) or UV/Vis and crystal forms that would not be characterized using traditional methods.

The TanDEM-X satellite mission has revolutionized DEM generation from spaceborne synthetic aperture radar. In addition to the primary objective of generating a consistent digital elevation model with global coverage and unprecedented accuracy, the mission has acquired time series of topographic data over several volcanoes, providing an excellent opportunity to test the use of this innovative dataset for volcano monitoring and research. In this article, we review the utilization of the single-pass TanDEM-X data for studying various kinds of volcanic activity, such as basaltic lava flows, the formation and destruction of lava domes and related pyroclastic density currents, and subsurface magma withdrawal and intrusion. We then consider the uses of these data for hazard assessment and forecasting. Our goal is to highlight the importance of timely and repeated topographic information in volcanology, and to suggest the development of future spaceborne bistatic synthetic aperture radar satellite missions, such as ESA's Earth Explorer 10 candidate mission, “Harmony.”

Widespread testing for the presence of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals remains vital for controlling the COVID-19 pandemic prior to the advent of an effective treatment. Challenges in testing can be traced to an initial shortage of supplies, expertise, and/or instrumentation necessary to detect the virus by quantitative RT-PCR (RT-qPCR), the most robust, sensitive, and specific assay currently available. Here we show that academic biochemistry and molecular biology laboratories equipped with appropriate expertise and infrastructure can replicate commercially available SARS-CoV-2 RT-qPCR test kits and backfill pipeline shortages. The Georgia Tech COVID-19 Test Kit Support Group, composed of faculty, staff, and trainees across the biotechnology quad at Georgia Institute of Technology, synthesized multiplexed primers and probes and formulated a master mix composed of enzymes and proteins produced in-house. Our in-house kit compares favorably with a commercial product used for diagnostic testing. We also developed an environmental testing protocol to readily monitor surfaces for the presence of SARS-CoV-2. Our blueprint should be readily reproducible by research teams at other institutions, and our protocols may be modified and adapted to enable SARS-CoV-2 detection in more resource-limited settings.

Since early 2020, disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, causing millions of infections and deaths worldwide. Despite rapid deployment of effective vaccines, it is apparent that the global community lacks multipronged interventions to combat viral infection and disease. A major limitation is the paucity of antiviral drug options representing diverse molecular scaffolds and mechanisms of action. Here we report the antiviral activities of three distinct marine natural products─homofascaplysin A (

The rise of antibiotic resistance has necessitated a search for new antimicrobials with potent activity against multidrug-resistant gram-negative pathogens, such as carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, a library of botanical extracts generated from plants used to treat infections in traditional medicine was screened for growth inhibition of CRAB. A crude extract of Schinus terebinthifolia leaves exhibited 80% inhibition at 256 µg/mL and underwent bioassay-guided fractionation, leading to the isolation of pentagalloyl glucose (PGG), a bioactive gallotannin. PGG inhibited growth of both CRAB and susceptible A. baumannii (MIC 64–256 µg/mL), and also exhibited activity against Pseudomonas aeruginosa (MIC 16 µg/mL) and Staphylococcus aureus (MIC 64 µg/mL). A mammalian cytotoxicity assay with human keratinocytes (HaCaTs) yielded an IC50 for PGG of 256 µg/mL. Mechanistic experiments revealed iron chelation as a possible mode of action for PGG’s activity against CRAB. Passaging assays for resistance did not produce any resistant mutants over a period of 21 days. In conclusion, PGG exhibits antimicrobial activity against CRAB, but due to known pharmacological restrictions in delivery, translation as a therapeutic may be limited to topical applications such as wound rinses and dressings.

The idea of the former Earth Explorer 10 mission Hydroterra is to place a SAR system into a geosynchronous orbit to understand rapid processes of the diurnal water cycle over regions of interest in Europe and Africa. The DLR Microwaves and Radar Institute conducted an airborne SAR campaign to support the Hydroterra mission. Airborne data were collected to simulate the long integration time of a geosynchronous SAR image and to evaluate the potential to detect diurnal moisture changes. In this paper the airborne campaign is described and the achieved results are presented.

Covering: January 2015 through December 2017 This review focuses on recent studies on the chemical ecology of planktonic marine ecosystems, with the objective of presenting a comprehensive overview of new findings in the field in the time period covered. In order to highlight the role of chemically mediated interactions in the marine plankton this review has been organized by ecological concepts starting with intraspecific communication, followed by interspecific interactions (including facilitation and mutualism, host-parasite, allelopathy, and predator-prey), and finally the effects of plankton secondary metabolites on community and ecosystem-wide interactions.

In the framework of its Earth Observation Programmes the European Space Agency (ESA) carries out ground based and airborne campaigns to support geophysical algorithm developments, calibration/validation activities, simulation of future space-borne earth observation missions, as well as application developments related to remote sensing of the atmosphere, land, oceans, solid earth and cryosphere.ESA has conducted over 150 airborne and ground based measurement campaigns in the last 37 years, of which more than 80 were carried out since 2005. During this period a large number of campaigns have supported the validation of ESA’s satellite missions including for example SMOS and CryoSat. Ongoing activities are focusing on e.g. Sentinel-5Precursor and the preparation of upcoming Earth Explorer missions such as BIOMASS, FLEX, and FORUM. These validation campaigns aim to provide fundamental information about the confidence of data products and their required uncertainties One challenge in this context is a comprehensive understanding and characterization of measurement uncertainty of the validation dataset and the spatial and temporal support or representativity of these.We will provide an overview of applied strategies to tackle these aspects for existing satellite missions and outline concepts for future missions, and how these integrate into broader earth observation science strategies. In addition, we will highlight recent activities and outline planned activities for the coming years.

Within the “Cooperation for the Use of Synthetic Aperture Radar Satellites in Earth Science and Applications”, the Japanese Aerospace Exploration Agency (JAXA) and the European Space Agency (ESA) agreed to mutually share C-band data from ESA’s Sentinel-1 mission and L-band data from JAXA’s ALOS-2 PALSAR-2 mission over selected test sites. Applications include wetland monitoring, hurricanes, sea ice, snow water equivalent and surface deformation.The aim of the collaboration is to develop a better understanding of the benefits of combining L- and C-band data over various areas and for the different thematic applications. The findings of the different European, Japanese and international projects will help to develop future SAR satellite missions, such as JAXA’s ALOS-4, and ESA’s Copernicus mission ROSE-L and Sentinel-1 Next Generation.This presentation will give an overview of the ongoing ESA-JAXA cooperation and will show highlights and first results of the different test sites and applications.

Harmful Algal Blooms (HABs) exert considerable ecological and economic damage and are becoming increasingly frequent worldwide. However, the biological factors underlying HABs remain uncertain. Relationships between algae and bacteria may contribute to bloom formation, strength, and duration. We investigated the microbial communities and metabolomes associated with a HAB of the toxic dinoflagellate Karenia brevis off the west coast of Florida in June 2018. Microbial communities and intracellular metabolite pools differed based on both bacterial lifestyle and bloom level, suggesting a complex role for blooms in reshaping microbial processes. Network analysis identified K. brevis as an ecological hub in the planktonic ecosystem, with significant connections to diverse microbial taxa. These included four flavobacteria and one sequence variant unidentified past the domain level, suggesting uncharacterized diversity in phytoplankton-associated microbial communities. Additionally, intracellular metabolomic analyses associated high K. brevis levels with higher levels of aromatic compounds and lipids. These findings reveal water column microbial and chemical characteristics with potentially important implications for understanding HAB onset and duration.

Covering: 2012 to 2017 This article reviews recent reports on the structural revision of natural products. Through a critical assessment of the original and revised published structures, the article addresses why each structure was targeted for revision, discusses the techniques and key discrepancies that led to the proposal of the revised structure, and offers measures that may have been taken during the original structure determination to prevent error. With the revised structures in hand, weaknesses of original proposals are assessed, providing a better understanding on the logic behind structure determination.

Recognition and rejection of chemically defended prey is critical to maximizing fitness for predators. Paralytic shellfish toxins (PSTs) which strongly inhibit voltage-gated sodium channels in diverse animal taxa are produced by several species of the bloom-forming algal genus Alexandrium where they appear to function as chemical defenses against grazing copepods. Despite PSTs being produced and localized within phytoplankton cells, some copepods distinguish toxic from non-toxic prey, selectively ingesting less toxic cells, in ways that suggest cell surface recognition perhaps associated with non-polar metabolites. In this study LC/MS and NMR-based metabolomics revealed that the non-polar metabolomes of two toxic species (Alexandrium catenella and Alexandrium pacificum) vary considerably from their non-toxic congener Alexandrium tamarense despite all three being very closely related. Toxic and non-toxic Alexandrium spp. were distinguished from each other by metabolites belonging to seven lipid classes. Of these, 17 specific metabolites were significantly more abundant in both toxic A. catenella and A. pacificum compared to non-toxic A. tamarense suggesting that just a small portion of the observed metabolic variability is associated with toxicity. Future experiments aimed at deciphering chemoreception mechanisms of copepod perception of Alexandrium toxicity should consider these metabolites, and the broader lipid classes phosphatidylcholines and sterols, as potential candidate cues.

Assessing eruption volumes is one of the major challenges in volcano research but provides valuable insights into the dynamics of an eruption and the associated hazard. One way to estimate this important parameter is the generation and differencing of digital elevation models (DEMs) acquired before, during, and after an eruption. The satellite mission TanDEM-X enables generation of time series of DEMs using synthetic aperture radar satellite imagery. We use these data to study the 2012–2013 eruption of Tolbachik in Kamchatka. We developed a processing scheme for generation of 18 DEMs from TanDEM-X imagery that relies on the generation of a preeruption DEM which is used to process the syneruption and posteruption data pairs. Differencing each DEM with the preeruption DEM enables mapping the lava flows and measuring lava flow volume over time and to estimate lava extrusion rates. We find a final lava flow volume of 0.53 km3 covering an area of 36 km2 by the end of the eruption. An uncertainty analysis is performed while analyzing the DEM differences in areas where no topographic change is expected, leading to an error of ±0.01 km3 for the final lava flow volume. The lava effusion was with 247.92 m3/s very high in the first days of the eruption and rapidly decayed toward its end. While many basaltic eruptions follow an exponentially decaying flow model, the extrusion rates at Tolbachik are more compatible with a 1/t model. This special characteristic might be useful to gain further insight into the eruption process at Tolbachik.

The Natural Product Reports themed issue on New Methods for Isolation and Structure Determination of Natural Products is introduced by the Guest Editors, Roger Linington, Julia Kubanek and Hendrik Luesch.

[Image: see text] Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A–B (1–2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.0(1,10).0(5,9)] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.

[Image: see text] A series of oligomeric phenols including the known natural product 3,4,3′,4′-tetrahydroxy-1,1′-biphenyl (3), the previously synthesized 2,3,8,9-tetrahydroxybenzo[c]chromen-6-one (4), and eight new related natural products, cladophorols B–I (5–12), were isolated from the Fijian green alga Cladophora socialis and identified by a combination of NMR spectroscopy, mass spectrometric analysis, and computational modeling using DFT calculations. J-resolved spectroscopy and line width reduction by picric acid addition aided in resolving the heavily overlapped aromatic signals. A panel of Gram-positive and Gram-negative pathogens used to evaluate pharmacological potential led to the determination that cladophorol C (6) exhibits potent antibiotic activity selective toward methicillin-resistant Staphylococcus aureus (MRSA) with an MIC of 1.4 μg/mL. Cladophorols B (5) and D–H (7–11) had more modest but also selective antibiotic potency. Activities of cladophorols A–I (4–12) were also assessed against the asexual blood stages of Plasmodium falciparum and revealed cladophorols A (4) and B (5) to have modest activity with EC(50) values of 0.7 and 1.9 μg/mL, respectively.

In this paper, we study long-term coastal flood risk of Lingang New City, Shanghai, considering 100- and 1000-year coastal flood return periods, local seal-level rise projections, and long-term ground subsidence projections. TanDEM-X satellite data acquired in 2012 were used to generate a high-resolution topography map, and multi-sensor InSAR displacement time-series were used to obtain ground deformation rates between 2007 and 2017. Both data sets were then used to project ground deformation rates for the 2030s and 2050s. A 2-D flood inundation model (FloodMap-Inertial) was employed to predict coastal flood inundation for both scenarios. The results suggest that the sea-level rise, along with land subsidence, could result in minor but non-linear impacts on coastal inundation over time. The flood risk will primarily be determined by future exposure and vulnerability of population and property in the floodplain. Although the flood risk estimates show some uncertainties, particularly for long-term predictions, the methodology presented here could be applied to other coastal areas where sea level rise and land subsidence are evolving in the context of climate change and urbanization.

An Overview of the Achievements of the "Integrated Analysis of the Combined Risk of Ground Subsidence Sea Level Rise, and Natural Hazards in Coastal Delta Regions

Covering: January 2013 to online publication December 2014 This review summarizes recent research in the chemical ecology of marine pelagic ecosystems, and aims to provide a comprehensive overview of advances in the field in the time period covered. In order to highlight the role of chemical cues and toxins in plankton ecology this review has been organized by ecological interaction types starting with intraspecific interactions, then interspecific interactions (including facilitation and mutualism, host–parasite, allelopathy, and predator–prey), and finally community and ecosystem-wide interactions.

In this work, we investigate the evolution of ground deformation in the Shanghai coastal region, China, over the last decade. We performed a Small BAseline subset DInSAR analysis based on the exploitation of three independent SAR datasets acquired by the ASAR/ENVISAT (ENV), COSMO-SkyMed (CSK), and Sentinel-1A (SlA) sensors, spanning the time frame between 2007 and 2017. More precisely, we used a time-dependent geotechnical centrifuge model of the subsidence signals to combine the available time-gapped CSK and ENV datasets, and hence we produced a long-term CSK, ENV, and SlA displacement time-series. The maximum subsidence rate calculated by the combined long-term ENV+CSK+S1A deformation time-series is about 30 mm/year. The achieved results are beneficial for future studies assessing the environmental risk (e.g., due to flooding) of the population living in the coastal area of Shanghai.

The formation, propagation, and maintenance of harmful algal blooms are of interest due to their negative effects on marine life and human health. Some bloom-forming algae utilize allelopathy, the release of compounds that inhibit competitors, to exclude other species dependent on a common pool of limiting resources. Allelopathy is hypothesized to affect bloom dynamics and is well established in the red tide dinoflagellate Karenia brevis. K. brevis typically suppresses competitor growth rather than being acutely toxic to other algae. When we investigated the effects of allelopathy on two competitors, Asterionellopsis glacialis and Thalassiosira pseudonana, using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS)-based metabolomics, we found that the lipidomes of both species were significantly altered. However, A. glacialis maintained a more robust metabolism in response to K. brevis allelopathy whereas T. pseudonana exhibited significant alterations in lipid synthesis, cell membrane integrity, and photosynthesis. Membrane-associated lipids were significantly suppressed for T. pseudonana exposed to allelopathy such that membranes of living cells became permeable. K. brevis allelopathy appears to target lipid biosynthesis affecting multiple physiological pathways suggesting that exuded compounds have the ability to significantly alter competitor physiology, giving K. brevis an edge over sensitive species.

An effective strategy for prey to survive in habitats rich in predators is to avoid being noticed. Thus, prey are under selection pressure to recognize predators and adjust their behavior, which can impact numerous community-wide interactions. Many animals in murky and turbulent aquatic environments rely on waterborne chemical cues. Previous research showed that the mud crab, Panopeus herbstii, recognizes the predatory blue crab, Callinectus sapidus, via a cue in blue crab urine. This cue is strongest if blue crabs recently preyed upon mud crabs. Subsequently, mud crabs suppress their foraging activity, reducing predation by blue crabs. Using NMR spectroscopy- and mass spectrometry-based metabolomics, chemical variation in urine from blue crabs fed different diets was related to prey behavior. We identified the urinary metabolites trigonelline and homarine as components of the cue that mud crabs use to detect blue crabs, with concentrations of each metabolite dependent on the blue crab’s diet. At concentrations found naturally in blue crab urine, trigonelline and homarine, alone as well as in a mixture, alerted mud crabs to the presence of blue crabs, leading to decreased foraging by mud crabs. Risk perception by waterborne cues has been widely observed by ecologists, but the molecular nature of these cues has not been previously identified. Metabolomics provides an opportunity to study waterborne cues where other approaches have historically failed, advancing our understanding of the chemical nature of a wide range of ecological interactions.

A flavobacterium protects a green alga and sea slug from predation

Accurate and up-to-date information on the time-varying topography of active volcanoes is crucial for assessing material flows through these volcanic systems and along their surfaces. As dome -building volcanoes can change on meter scale within short time intervals in active phases, conventionally used repeat-pass SAR-interferometry (InSAR) often fails due to decorrelation effects, while other methods to measure topography like aerial photogrammetry or Lidar depend on the availability of the local infrastructure and on good weather conditions. Here, we show the potential of the spaceborne Earth observation mission TanDEM-X to monitor topographic changes at active dome-building volcanoes. In this innovative satellite mission, two nearly identical satellites fly in a close formation, taking radar images of the Earth's surface at the same time in bistatic mode. This opens the possibility to generate digital elevation models (DEMs) of volcanoes. Analyzing a series of repeated DEMs enables assessment of volume changes caused by lava dome activity. We apply this method to Merapi in Indonesia by analyzing the volume changes during the hazardous 2010 eruption. During this eruption, the old lava dome collapsed, and a new lava dome was extruded which collapsed again within twelve days. We show three DEMs derived from bistatic TanDEM-X InSAR in descending orbit taken before and after the eruption. We found a mean volume change of 19 × 10 6 m 3 in the summit area. The two estimates differ by 0.4 × 10 6 m 3 which is 2% of the average dome volume change. The TanDEM-X based results are about 25% lower than reference data, which can be explained by the shadow masks that were introduced to exclude geometrically decorrelated areas, resulting in conservative volume change estimates.

Many organisms encounter noxious or unpalatable compounds in their diets. Thus, a robust reception-system for aversive taste is necessary for an individual's survival; however, mechanisms for perceiving aversive taste vary among organisms. Possession of a system sensitive to aversive taste allows for recognition of a vast array of noxious molecules via membrane-bound receptors, co-receptors, and ion channels. These receptor-ligand interactions trigger signal transduction pathways resulting in activation of nerves and in neural processing, which in turn dictates behavior, including rejection of the noxious item. The impacts of these molecular processes on behavior differ among species, and these differences have impacts at the ecosystem level by driving feeding-behavior, organization of communities, and ultimately, speciation. For example, when comparing mammalian carnivores and herbivores, it is not surprising that herbivores that encounter a variety of toxic plants in their diets express a larger number of aversive taste receptors than carnivores. Comparing the molecular mechanisms and ecological consequences of aversive-taste reception among organisms in a variety of types of ecosystems and ecological niches will illuminate the role of taste in ecology and evolution.

Harmful algae are known to utilize allelopathy, the release of compounds that inhibit competitors, as a form of interference competition. Competitor responses to allelopathy are species-specific and allelopathic potency of producing algae is variable. In the current study, the biological variability in allelopathic potency was mapped to the underlying chemical variation in the exuded metabolomes of five genetic strains of the red tide dinoflagellate Karenia brevis using

Fishes rely on both chemical and tactile senses to orient themselves to avoid predators, and to detect and taste food. This is likely achieved by highly coordinated reception of signals by mechano- and chemosensory receptors in fish. A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)-like triterpene glycoside receptor (RL-TGR), was previously found to be involved in recognition of triterpene glycosides, a family of naturally occurring compounds that act as chemical defenses in various prey species. However, its localization, function, and how it impacts sensory organ development in vivo is not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical microvilli of the chemosensory cells of taste buds including the epithelium of lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts belonging to the lateral line system. Loss-of-function analyses of RL-TGR resulted in significantly decreased number of neuromasts in the posterior lateral line system and decreased body length, suggesting that RL-TGR is involved in deposition and migration of the neuromasts. Collectively, these results provide the first in vivo genetic evidence of sensory cell-specific expression of this unusual co-receptor and reveal its additional role in the lateral line development in zebrafish.

Unique iodine-containing meroditerpenes io-docallophycoic acid A (1) and iodocallophycols A–D (2–5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL−1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL−1.