Total Synthesis and Structural Reassignment of the Molt-Inhibiting Marine Alkaloid Erebusinone.

The marine alkaloid erebusinone is a secondary metabolite isolated from the Antarctic sponge . Initial biological assays have shown that erebusinone increases amphipod mortality, probably by inhibition of the biosynthesis of molting hormone (ecdysone). Herein, we report the first total synthesis of the proposed structure of erebusinone and a structural revision.

Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids.

Two novel pyrroloiminoquinone alkaloids, 6-chlorodamirone A and 6-bromodamirone A, have been identified for the first time from the marine sponge sp. (order: Poecilosclerida: family Latrunculiidae), sourced from Western Australia. Alongside these new compounds, seven previously known metabolites were also isolated.

Motherhood and Drinking: The Relative Importance of Mental Health and Psychosocial Factors on Maternal Alcohol Misuse During the Postpartum Period.

Objective: Being a mother of a young child may be protective against alcohol misuse for some, but not all, women. This is the first study to identify the mental health and psychosocial correlates of alcohol misuse among postpartum mothers.

Method: Mothers with a child younger than 12 months ( = 319) were recruited via social media to complete a cross-sectional online survey.

Museum Skins Enable Identification of Introgression Associated with Cytonuclear Discordance.

Increased sampling of genomes and populations across closely related species has revealed that levels of genetic exchange during and after speciation are higher than previously thought. One obvious manifestation of such exchange is strong cytonuclear discordance, where the divergence in mitochondrial DNA (mtDNA) differs from that for nuclear genes more (or less) than expected from differences between mtDNA and nuclear DNA (nDNA) in population size and mutation rate. Given genome-scale data sets and coalescent modeling, we can now confidently identify cases of strong discordance and test specifically for historical or recent introgression as the cause.

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

Background: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects.

Web-Based Cognitive Bias Modification Program for Young People With Social Anxiety and Hazardous Alcohol Use: Feasibility, Acceptability, and Preliminary Efficacy Study.

Background: Interpretation bias modification (IBM) and approach bias modification (ApBM) cognitive retraining interventions can be efficacious adjunctive treatments for improving social anxiety and alcohol use problems. However, previous trials have not examined the combination of these interventions in a young, comorbid sample.

Objective: This study aims to describe the feasibility, acceptability, and preliminary efficacy of a web-based IBM+ApBM program for young adults with social anxiety and hazardous alcohol use ("Re-Train Your Brain") when delivered in conjunction with treatment as usual (TAU).

An Orthogonal Conductance Pathway in Spiropyrans for Well-Defined Electrosteric Switching Single-Molecule Junctions.

While a multitude of studies have appeared touting the use of molecules as electronic components, the design of molecular switches is crucial for the next steps in molecular electronics. In this work, single-molecule devices incorporating spiropyrans, made using break junction techniques, are described. Linear spiropyrans with electrode-contacting groups linked by alkynyl spacers to both the indoline and chromenone moieties have previously provided very low conductance values, and removing the alkynyl spacer has resulted in a total loss of conductance.

Multistate Switching of Some Ruthenium Alkynyl and Vinyl Spiropyran Complexes.

To study the switching properties of photochromes, we undertook the synthesis and characterization of several ruthenium organometallic complexes of the type [Ru(Cp*)(dppe)(C≡C-SP)] or [Ru(CO)(dppe)(PPh)Cl(CH═CH-SP)], where SP = spiropyran. The spectroscopic and electrochemical properties of the complexes were determined by careful cyclic voltammetric and spectroelectrochemical experiments. Whereas the mononuclear alkynyl ruthenium complexes undergo one-electron oxidations localized over the metal alkynyl moiety, the oxidation of the mononuclear vinyl ruthenium complexes is centered on the indoline moiety of the spiropyran.

Synthesis, Characterization, and Bioactivity of the Lichen Pigments Pulvinamide, Rhizocarpic Acid, and Epanorin and Congeners.

The lichen natural products pulvinamide, rhizocarpic acid, and epanorin have been synthesized and characterized spectroscopically and by X-ray crystallography. The syntheses, by ring-opening of pulvinic acid dilactone (PAD), may well be biomimetic, given the well-known occurrence of PAD in lichen. The enantiomers, -rhizocarpic acid and -epanorin, and corresponding carboxylic acids, norrhizocarpic acid and norepanorin, were similarly prepared.

Multifunctional switching properties of "wire-like" dinuclear ruthenium bis-alkynyl spiropyran complexes.

Multifunctional switches are crucial to the development of smart molecular materials and molecular-electronic applications. Here, we describe the synthesis, structure, and characterization of several spiropyrans functionalized with alkynyl-[Ru(dppe)] moieties. Through electrochemical and spectroelectrochemical studies, we demonstrate access to several stable redox states, in addition to states accessed acidochromism and photoisomerisation.

Sea-level rise will likely accelerate rock coast cliff retreat rates.

Coastal response to anthropogenic climate change is of central importance to the infrastructure and inhabitants in these areas. Despite being globally ubiquitous, the stability of rock coasts has been largely neglected, and the expected acceleration of cliff erosion following sea-level rise has not been tested with empirical data, until now. We have optimised a coastal evolution model to topographic and cosmogenic radionuclide data to quantify cliff retreat rates for the past 8000 years and forecast rates for the next century.

Investigating microscale patchiness of motile microbes under turbulence in a simulated convective mixed layer.

Microbes play a primary role in aquatic ecosystems and biogeochemical cycles. Spatial patchiness is a critical factor underlying these activities, influencing biological productivity, nutrient cycling and dynamics across trophic levels. Incorporating spatial dynamics into microbial models is a long-standing challenge, particularly where small-scale turbulence is involved.

Development of a gamma ray dose rate calculation and mapping tool for Lagrangian marine nuclear emergency response models.

This paper presents the development and testing of a gamma radiation dose rate calculation model for the marine environment, and evaluates the potential use for such a model in both short term nuclear emergency response management and emergency response planning. This is believed to be the first implementation of a full field gamma radiation mapping model (including air attenuation and buildup) to be incorporated within a Lagrangian marine dispersion model. Calculated surface gamma ray dose rates for nine generic release scenarios are presented and used to undertake an emergency countermeasure optioneering assessment.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described.

Toward the Total Synthesis of Alpkinidine: Michael Addition to Isoquinolinetrione CE Ring-System Synthons.

Strategies toward the total synthesis of the marine pyrroloacridine alkaloid alpkinidine have been explored, focusing on linking quinonoid CE ring-system synthons with the A ring, followed by condensation to form the B and D rings. The key Michael addition of the ester enolate derived from ethyl -nitrophenylacetate to 2-methylisoquinoline-1,5,8(2)-trione proceeded with the wrong regiochemistry. This issue was addressed by incorporating the D-ring nitrogen at an earlier stage, affording advanced intermediates possessing the complete carbon skeleton of alpkinidine.

Toward the Total Synthesis of Alpkinidine: Synthesis of Haloquinone CE Ring System Synthons and Attempted Nucleophilic Bisannulation.

Model chemistry involving the bisannulation of 2,3-dichloro-1,4-naphthoquinone with the ester enolate derived from ethyl -nitrophenylacetic acid, which rapid assembled the ABCD ring system of a pentacyclic pyrroloacridine, has been applied to the attempted synthesis of the marine natural product alpkinidine. The reaction of ethyl -nitrophenylacetic acid with 6,7-dichloro-2-methylisoquinoline-1,5,8(2)-trione, required to extend the model strategy to alpkinidine, was unfruitful, giving only complex mixtures. Efforts to direct the regiochemistry of the key Michael substitution step using 6-bromo-2-methylisoquinoline-1,5,8(2)-trione afforded an adduct sharing the complete carbon skeleton of alpkinidine, but this could not be elaborated to the natural product.

A review of the UK and British Channel Islands practical tidal stream energy resource.

This review provides a critical, multi-faceted assessment of the practical contribution tidal stream energy can make to the UK and British Channel Islands future energy mix. Evidence is presented that broadly supports the latest national-scale practical resource estimate, of 34 TWh/year, equivalent to 11% of the UK's current annual electricity demand. The size of the practical resource depends in part on the economic competitiveness of projects.

PPARα and PPARγ activation is associated with pleural mesothelioma invasion but therapeutic inhibition is ineffective.

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth.

A Web-Based Cognitive Bias Modification Intervention (Re-train Your Brain) for Emerging Adults With Co-occurring Social Anxiety and Hazardous Alcohol Use: Protocol for a Multiarm Randomized Controlled Pilot Trial.

Background: Alcohol use and anxiety disorders commonly co-occur, resulting in a more severe clinical presentation and poorer response to treatment. Research has shown that approach bias modification (ApBM) and interpretation bias modification (IBM) cognitive retraining interventions can be efficacious adjunctive treatments that improve outcomes for alcohol use and social anxiety, respectively. However, the acceptability, feasibility, and clinical utility of combining ApBM and IBM programs to optimize treatments among comorbid samples are unknown.

Isotope-Coded Maleimide Affinity Tags for Proteomics Applications.

Isotope-coded affinity tags (ICATs) are valuable tools for mass spectrometry-based quantitative proteomics, in particular, for comparison of protein (cysteine-residue) thiol oxidation state in normal, stressed, and diseased tissue. However, the iodoacetamido electrophile used in most commercial ICATs suffers from poor thiol-selectivity and modest rates of adduct formation, which can lead to spurious results. Hence, we designed and synthesized three ICATs containing thiol-selective -alkylmaleimide electrophiles (isotope-coded maleimide affinity tags = ICMATs) and assessed these as mass spectrometry probes for ratiometric analysis of lysozyme and muscle proteomes.

Total Synthesis of the Antitumor-Antitubercular 2,6'-Bijuglone Natural Product Diospyrin and Its 3,6'-Isomer.

The 2,6'-bijuglone natural product diospyrin and its unnatural 3,6'-isomer idospyrin have been synthesized in seven steps each from ,-diethylsenecioamide in overall yields of 12% and 13%, respectively. The syntheses diverge from ramentaceone (7-methyljuglone) and include a key Suzuki-Miyaura cross-coupling. Diospyrin, idospyrin, and several synthetic precursors exhibit potent and selective cytotoxicity to the murine myeloma NS-1 cell line over neonatal foreskin cells.

Acceptability and Co-Development of an Online Cognitive Bias Modification Intervention for Emerging Adults With Hazardous Alcohol Use and Social Anxiety: A Mixed Methods Study.

Background: Approach bias modification (ApBM) and interpretation bias modification (IBM) are two promising adjunct treatments for alcohol use and social anxiety, respectively. However, the acceptability of combining ApBM and IBM into one program for people who experience both of these disorders is unknown. The present study describes the codevelopment of a new, hybrid ApBM + IBM program and provides insight into the perceptions of acceptability from service providers and emerging adults.

New insights on tidal dynamics and tidal energy harvesting in the Alderney Race.

The Introduction presents motivations, significance and some key points of the research activities performed in the Alderney Race. This article is part of the theme issue 'New insights on tidal dynamics and tidal energy harvesting in the Alderney Race'.

Identifying economically viable tidal sites within the Alderney Race through optimization of levelized cost of energy.

Costs of tidal stream energy generation are anticipated to fall considerably with array expansion and time. This is due to both economies of volume, where arrays comprising of large numbers of turbines can split fixed costs over a greater number of devices, and learning rates, where the industry matures and so arrays of the same size become cheaper due to lessons learned from previous installations. This paper investigates how tidal energy arrays can be designed to minimize the levelized cost of energy (LCOE), by optimizing not only the location but also the number of devices, to find a suitable balance between decreased costs due to economies of volume and diminishing returns due to global blockage effects.