Anthoteibinenes F-Q: New Sesquiterpenes from the Irish Deep-Sea Coral .

New technology has opened opportunities for research and exploration of deep-water ecosystems, highlighting deep-sea coral reefs as a rich source of novel bioactive natural products. During our ongoing investigation of the chemodiversity of the Irish deep sea and the soft coral we report 12 unreported cadinene-like functionalized sesquiterpenes, anthoteibinenes F-Q. The metabolites were isolated using both bioassay- and H NMR-guided approaches.

Circumpolar and Regional Seascape Drivers of Genomic Variation in a Southern Ocean Octopus.

Understanding how ecological, environmental and geographic features influence population genetic patterns provides crucial insights into a species' evolutionary history, as well as their vulnerability or resilience under climate change. In the Southern Ocean, population genetic variation is influenced across multiple spatial scales ranging from circum-Antarctic, which encompasses the entire continent, to regional, with varying levels of geographic separation. However, comprehensive analyses testing the relative importance of different environmental and geographic variables on genomic variation across these scales are generally lacking in the Southern Ocean.

A new genus of bamboo coral (Octocorallia: Scleralcyonacea: Keratoisididae) from the Whittard Canyon, Ireland, Northeast Atlantic.

Deep-sea corals are rarely identified to species due to a lack of taxonomic expertise and paucity of sampling. Herein we describe a new genus from the family Keratoisididae collected from the Northeast Atlantic. Using both nuclear (2010 conserved element loci) and complete mitogenome phylogenies, we found this genus to be closely related to the genera Dokidisis and Jasonisis .

Anthoteibinenes A-E from the Irish Deep-Sea Coral : An Amination Puzzle.

Chemical investigation of extracts from the Irish deep-sea soft coral revealed cadinene-like sesquiterpenes, anthoteibinenes A-E, bearing unusual dimethylamine substitution. Structure elucidation was accomplished using 1D/2D NMR spectroscopy and high-resolution mass spectrometry, while NOESY NMR experiments, gauge invariant atomic orbital (GIAO) NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose their relative and absolute configurations. Anthoteibinene B () exhibited 49% inhibition of respiratory syncytial virus (RSV) at 3.

Genomic evidence for West Antarctic Ice Sheet collapse during the Last Interglacial.

The marine-based West Antarctic Ice Sheet (WAIS) is considered vulnerable to irreversible collapse under future climate trajectories, and its tipping point may lie within the mitigated warming scenarios of 1.5° to 2°C of the United Nations Paris Agreement. Knowledge of ice loss during similarly warm past climates could resolve this uncertainty, including the Last Interglacial when global sea levels were 5 to 10 meters higher than today and global average temperatures were 0.

Mapping the epigenomic landscape of human monocytes following innate immune activation reveals context-specific mechanisms driving endotoxin tolerance.

Background: Monocytes are key mediators of innate immunity to infection, undergoing profound and dynamic changes in epigenetic state and immune function which are broadly protective but may be dysregulated in disease. Here, we aimed to advance understanding of epigenetic regulation following innate immune activation, acutely and in endotoxin tolerant states.

Methods: We exposed human primary monocytes from healthy donors (n = 6) to interferon-γ or differing combinations of endotoxin (lipopolysaccharide), including acute response (2 h) and two models of endotoxin tolerance: repeated stimulations (6 + 6 h) and prolonged exposure to endotoxin (24 h).

Atlantic Oceanic Squids in the "Grey Speciation Zone".

Cryptic species complexes represent an important challenge for the adequate characterization of Earth's biodiversity. Oceanic organisms tend to have greater unrecognized cryptic biodiversity since the marine realm was often considered to lack hard barriers to genetic exchange. Here, we tested the effect of several Atlantic and Mediterranean oceanic barriers on 16 morphospecies of oceanic squids of the orders Oegopsida and Bathyteuthida using three mitochondrial and one nuclear molecular marker and five species delimitation methods.

A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery.

Objective: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia.

Background: Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality.

Methods: From a prospective consecutive cohort (n=150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2-6, 24, and 48 h).

Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common, highly heritable inflammatory arthritis characterized by enthesitis of the spine and sacroiliac joints. Genome-wide association studies (GWASs) have revealed more than 100 genetic associations whose functional effects remain largely unresolved. Here, we present a comprehensive transcriptomic and epigenomic map of disease-relevant blood immune cell subsets from AS patients and healthy controls.

Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis.

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils.

Genome skimming elucidates the evolutionary history of Octopoda.

Phylogenies for Octopoda have, until now, been based on morphological characters or a few genes. Here we provide the complete mitogenomes and the nuclear 18S and 28S ribosomal genes of twenty Octopoda specimens, comprising 18 species of Cirrata and Incirrata, representing 13 genera and all five putative families of Cirrata (Cirroctopodidae, Cirroteuthidae, Grimpoteuthidae, Opisthoteuthidae and Stauroteuthidae) and six families of Incirrata (Amphitretidae, Argonautidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, and Megaleledonidae) which were assembled using genome skimming. Phylogenetic trees were built using Maximum Likelihood and Bayesian Inference with several alignment matrices.

Sea spiders (Arthropoda, Pycnogonida) from ten recent research expeditions to the Antarctic Peninsula, Scotia Arc and Weddell Sea - data.

Background: This dataset contains information on specimens of Southern Ocean Pycnogonida (Arthropoda), that were collected from ten different research cruises, spanning 13 years. The individual aims and objectives of each cruise can be found in their cruise reports. The specimens have been collated into a single dataset, forming the basis of J.

Tuaimenals B-H, Merosesquiterpenes from the Irish Deep-Sea Soft Coral with Bioactivity against Cervical Cancer Cell Lines.

Previous chemical investigation of the Irish deep-sea soft coral led to the identification of tuaimenal A (), a new merosesquiterpene containing a highly substituted chromene core and modest cytotoxicity against cervical cancer. Further MS/MS and NMR-guided investigation of this octocoral has resulted in the isolation and characterization of seven additional tuaimenal analogs, B-H (-), as well as two known A-ring aromatized steroids (, ), and additional tuaimenal A (). Tuaimenals B, F, and G (, , ), bearing an oxygen at the C position, as well as monocyclic tuaimenal H (), show increased cervical cancer inhibition profiles in comparison to that of .

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map.

Evolution of mitochondrial and nuclear genomes in Pennatulacea.

We examine the phylogeny of sea pens using sequences of whole mitochondrial genomes and the nuclear ribosomal cluster generated through low coverage Illumina sequencing. Taxon sampling includes 30 species in 19 genera representing 13 families. Ancestral state reconstruction shows that most sea pen mitochondrial genomes have the ancestral gene order, and that Pennatulacea with diverse gene orders are found in a single clade.

Crannenols A-D, Sesquiterpenoids from the Irish Deep-Sea Soft Coral .

Four undescribed sesquiterpenoids, crannenols A-D (-), have been isolated from CHCl and MeOH extracts of the deep-sea bamboo coral . The corals were collected from a submarine canyon on the edge of Ireland's Porcupine Bank via a remotely operated vehicle. The structure elucidation of these (,)-α-farnesene derivatives was achieved using a combination of 1D and 2D NMR, electron impact (, ), and electrospray ionization (, ) mass spectrometry.

Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance.

Background: Chromatin states and enhancers associate gene expression, cell identity and disease. Here, we systematically delineate the acute innate immune response to endotoxin in terms of human macrophage enhancer activity and contrast with endotoxin tolerance, profiling the coding and non-coding transcriptome, chromatin accessibility and epigenetic modifications.

Results: We describe the spectrum of enhancers under acute and tolerance conditions and the regulatory networks between these enhancers and biological processes including gene expression, splicing regulation, transcription factor binding and enhancer RNA signatures.

Tuaimenal A, a Meroterpene from the Irish Deep-Sea Soft Coral , Displays Inhibition of the SARS-CoV-2 3CLpro Enzyme.

Cold water benthic environments are a prolific source of structurally diverse molecules with a range of bioactivities against human disease. Specimens of a previously chemically unexplored soft coral, , were collected during a deep-sea cruise that sampled marine invertebrates along the Irish continental margin in 2018. Tuaimenal A (), a cyclized merosesquiterpenoid representing a new carbon scaffold with a highly substituted chromene core, was discovered through exploration of the soft coral secondary metabolome via NMR-guided fractionation.

Optimization of LC-MS Data Acquisition Parameters for Molecular Networking Applied to Marine Natural Products.

Since the introduction of the online open-source GNPS, molecular networking has quickly become a widely applied tool in the field of natural products chemistry, with applications from dereplication, genome mining, metabolomics, and visualization of chemical space. Studies have shown that data dependent acquisition (DDA) parameters affect molecular network topology but are limited in the number of parameters studied. With an aim to optimize LC-MS parameters for integrating GNPS-based molecular networking into our marine natural products workflow, a design of experiment (DOE) was used to screen the significance of the effect that eleven parameters have on both Classical Molecular Networking workflow (CLMN) and the new Feature-Based Molecular Networking workflow (FBMN).

Marine Robotics for Deep-Sea Specimen Collection: A Taxonomy of Underwater Manipulative Actions.

In order to develop a gripping system or control strategy that improves scientific sampling procedures, knowledge of the process and the consequent definition of requirements is fundamental. Nevertheless, factors influencing sampling procedures have not been extensively described, and selected strategies mostly depend on pilots' and researchers' experience. We interviewed 17 researchers and remotely operated vehicle (ROV) technical operators, through a formal questionnaire or in-person interviews, to collect evidence of sampling procedures based on their direct field experience.

Unveiling the Chemical Diversity of the Deep-Sea Sponge .

Sponges are at the forefront of marine natural product research. In the deep sea, extreme conditions have driven secondary metabolite pathway evolution such that we might expect deep-sea sponges to yield a broad range of unique natural products. Here, we investigate the chemodiversity of a deep-sea tetractinellid sponge, , collected from ~800 m depth in Irish waters.

Not Drug-like, but Like Drugs: Cnidaria Natural Products.

Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after excluding those known to derive from microbial symbionts), using a systematic approach based on chemical space, drug-likeness, predicted toxicity, and virtual screens.

Deep-Sea Coral Garden Invertebrates and Their Associated Fungi Are Genetic Resources for Chronic Disease Drug Discovery.

Chronic diseases characterized by bone and cartilage loss are associated with a reduced ability of progenitor cells to regenerate new tissues in an inflammatory environment. A promising strategy to treat such diseases is based on tissue repair mediated by human mesenchymal stem cells (hMSCs), but therapeutic outcomes are hindered by the absence of small molecules to efficiently modulate cell behaviour. Here, we applied a high-throughput drug screening technology to bioprospect a large library of extracts from Irish deep-sea organisms to induce hMSC differentiation toward musculoskeletal lineages and reduce inflammation of activated macrophages.