Review: Marine natural products

This review covers the literature published in 2003 for marine natural products, with 619 citations (413 for the period January to December 2003) referring to compounds isolated from marine microorganisms and phytoplankton, green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates and echinoderms. The emphasis is on new compounds (656 for 2003), together with their relevant biological activities, source organisms and country of origin. Biosynthetic studies or syntheses that lead to the revision of structures or stereochemistries have been included (78), including any first total syntheses of a marine natural product

The Isolation of a New S-Methyl Benzothioate Compound from a Marine-Derived Streptomyces sp.

The application of an HPLC bioactivity profiling/microtiter plate technique in conjunction with microprobe NMR instrumentation and access to the AntiMarin database has led to the isolation of a new 1. In this example, 1 was isolated from a cytotoxic fraction of an extract obtained from marine-derived Streptomyces sp. cultured on Starch Casein Agar (SCA) medium. The 1D and 2D 1H NMR and ESIMS data obtained from 20 μg of compound 1 fully defined the structure. The known 2 was also isolated and readily dereplicated using this approach

Trends in the Discovery of New Marine Natural Products from Invertebrates over the Last Two Decades – Where and What Are We Bioprospecting?

It is acknowledged that marine invertebrates produce bioactive natural products that may be useful for developing new drugs. By exploring untapped geographical sources and/or novel groups of organisms one can maximize the search for new marine drugs to treat human diseases. The goal of this paper is to analyse the trends associated with the discovery of new marine natural products from invertebrates (NMNPI) over the last two decades. The analysis considers different taxonomical levels and geographical approaches of bioprospected species. Additionally, this research is also directed to provide new insights into less bioprospected taxa and world regions. In order to gather the information available on NMNPI, the yearly-published reviews of Marine Natural Products covering 1990–2009 were surveyed. Information on source organisms, specifically taxonomical information and collection sites, was assembled together with additional geographical information collected from the articles originally describing the new natural product. Almost 10000 NMNPI were discovered since 1990, with a pronounced increase between decades. Porifera and Cnidaria were the two dominant sources of NMNPI worldwide. The exception was polar regions where Echinodermata dominated. The majority of species that yielded the new natural products belong to only one class of each Porifera and Cnidaria phyla (Demospongiae and Anthozoa, respectively). Increased bioprospecting efforts were observed in the Pacific Ocean, particularly in Asian countries that are associated with the Japan Biodiversity Hotspot and the Kuroshio Current. Although results show comparably less NMNPI from polar regions, the number of new natural products per species is similar to that recorded for other regions. The present study provides information to future bioprospecting efforts addressing previously unexplored taxonomic groups and/or regions. We also highlight how marine invertebrates, which in some cases have no commercial value, may become highly valuable in the ongoing search for new drugs from the sea

Marine natural products

This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included

Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres

Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long-terminal-repeat (non-LTR) retrotransposons that comprise 17% of human DNA(1). The average human genome contains similar to 80-100 retrotransposition- competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription(3-5). We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (ENi) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end-joining (NHEJ) pathway of DNA double-strand-break repair(6). Here we have characterized ENi retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, similar to 30% of ENi retrotransposition events insert in an orientation-specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among ENi retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 ( also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated ENi retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of ENi retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends(7,8). Thus, we propose that ENi retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62964/1/nature05560.pd

Radial Velocity Discovery of an Eccentric Jovian World Orbiting at 18 au

Based on two decades of radial velocity (RV) observations using Keck/High Resolution Echelle Spectrometer (HIRES) and McDonald/Tull, and more recent observations using the Automated Planet Finder, we found that the nearby star HR 5183 (HD 120066) hosts a 3 minimum mass planet with an orbital period of yr. The orbit is highly eccentric (e ≃ 0.84), shuttling the planet from within the orbit of Jupiter to beyond the orbit of Neptune. Our careful survey design enabled high cadence observations before, during, and after the planet\u27s periastron passage, yielding precise orbital parameter constraints. We searched for stellar or planetary companions that could have excited the planet\u27s eccentricity, but found no candidates, potentially implying that the perturber was ejected from the system. We did identify a bound stellar companion more than 15,000 au from the primary, but reasoned that it is currently too widely separated to have an appreciable effect on HR 5183 b. Because HR 5183 b\u27s wide orbit takes it more than 30 au (1\u27\u27) from its star, we also explored the potential of complimentary studies with direct imaging or stellar astrometry. We found that a Gaia detection is very likely, and that imaging at 10 μm is a promising avenue. This discovery highlights the value of long-baseline RV surveys for discovering and characterizing long-period, eccentric Jovian planets. This population may offer important insights into the dynamical evolution of planetary systems containing multiple massive planets

Environment-driven variability in absolute band edge positions and work functions of reduced ceria

The absolute band edge positions and work function (Φ) are the key electronic properties of metal oxides that determine their performance in electronic devices and photocatalysis. However, experimental measurements of these properties often show notable variations, and the mechanisms underlying these discrepancies remain inadequately understood. In this work, we focus on ceria (CeO2), a material renowned for its outstanding oxygen storage capacity, and combine theoretical and experimental techniques to demonstrate environmental modifications of its ionization potential (IP) and Φ. Under O-deficient conditions, reduced ceria exhibits a decreased IP and Φ with significant sensitivity to defect distributions. In contrast, the IP and Φ are elevated in O-rich conditions due to the formation of surface peroxide species. Surface adsorbates and impurities can further augment these variabilities under realistic conditions. We rationalize the shifts in energy levels by separating the individual contributions from bulk and surface factors, using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded-cluster and periodic density functional theory (DFT) calculations supported by interatomic-potential-based electrostatic analyses. Our results highlight the critical role of on-site electrostatic potentials in determining the absolute energy levels in metal oxides, implying a dynamic evolution of band edges under catalytic conditions

Bright Opportunities for Atmospheric Characterization of Small Planets: Masses and Radii of K2-3 b, c, and d and GJ3470 b from Radial Velocity Measurements and Spitzer Transits

We report improved masses, radii, and densities for four planets in two bright M-dwarf systems, K2-3 and GJ3470, derived from a combination of new radial velocity and transit observations. Supplementing K2 photometry with follow-up Spitzer transit observations refined the transit ephemerides of K2-3 b, c, and d by over a factor of 10. We analyze ground-based photometry from the Evryscope and Fairborn Observatory to determine the characteristic stellar activity timescales for our Gaussian Process fit, including the stellar rotation period and activity region decay timescale. The stellar rotation signals for both stars are evident in the radial velocity data and is included in our fit using a Gaussian process trained on the photometry. We find the masses of K2-3 b, K2-3 c, and GJ3470 b to be 6.48{}-0.93+0.99, 2.14{}-1.04+1.08, and 12.58{}-1.28+1.31 M ⊕, respectively. K2-3 d was not significantly detected and has a 3σ upper limit of 2.80 M ⊕. These two systems are training cases for future TESS systems; due to the low planet densities (ρ < 3.7 g cm-3) and bright host stars (K < 9 mag), they are among the best candidates for transmission spectroscopy in order to characterize the atmospheric compositions of small planets

Discovery of a Novel, Isothiazolonaphthoquinone-Based Small Molecule Activator of FOXO Nuclear-Cytoplasmic Shuttling

FOXO factors are tumour suppressor proteins commonly inactivated in human tumours by posttranslational modifications. Furthermore, genetic variation within the FOXO3a gene is consistently associated with human longevity. Therefore, the pharmacological activation of FOXO proteins is considered as an attractive therapeutic approach to treat cancer and age-related diseases. In order to identify agents capable of activating FOXOs, we tested a collection of small chemical compounds using image-based high content screening technology. Here, we report the discovery of LOM612 (compound 1a), a newly synthesized isothiazolonaphthoquinone as a potent FOXO relocator. Compound 1a induces nuclear translocation of a FOXO3a reporter protein as well as endogenous FOXO3a and FOXO1 in U2OS cells in a dose-dependent manner. This activity does not affect the subcellular localization of other cellular proteins including NFkB or inhibit CRM1-mediated nuclear export. Furthermore, compound 1a shows a potent antiproliferative effect in human cancer cell lines