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The Antarctic marine environment, although rich in life, is predicted to experience rapid and significant effects from climate change. Despite a revolution in the approaches used to document biodiversity, less than one percent of Antarctic marine invertebrates are represented by DNA barcodes and we are at risk of losing biodiversity before discovery. The ease of sequencing mitochondrial DNA barcodes has promoted this relatively ‘universal’ species identification system across most metazoan phyla and barcode datasets are currently readily used for exploring questions of species-level taxonomy. Here we present the most well-sampled phylogeny of the direct-developing, Southern Ocean nudibranch mollusc, Doris kerguelenensis to date. This study sampled over 1000 new Doris kerguelenensis specimens spanning the Southern Ocean and sequenced the mitochondrial COI gene. Results of a maximum likelihood phylogeny and multiple subsequent species delimitation analyses identified 27 new species in this complex (now 59 in total). Using rarefaction techniques, we infer more species are yet to be discovered. Some species were only collected from southern South America or the sub-Antarctic islands, while at least four species were found spanning the Polar Front. This is contrary to dispersal predictions for species without a larval stage such as Doris kerguelenensis. Our work demonstrates the value of increasing geographic scope in sampling and highlights what could be lost given the current global biodiversity crisis.

The dielectric breakdown strength of solid insulators is usually dependent on the dimensions of the sample. In particular, for "thick" insulating sheets having thicknesses above a certain threshold thickness of typically about 10 micrometer, the dielectric breakdown strength at room temperature is often found to be roughly proportional to the inverse of the square root of the sample thickness. In this contribution, the hypothesis is examined that the latter type of size dependence is related to electric field inhomogeneities associated with the geometrical electrode configuration. In order to test the hypothesis, dielectric breakdown experiments have been performed for alumina ceramic sheets of different thicknesses. In this context, an electrode configuration has been used which allows for an analysis of the local electric field enhancement at the electrode edge in terms of fracture mechanics concepts. It is concluded from a comparison of experimental and theoretical results that the mentioned dependence of the dielectric breakdown strength on sample thickness is, under certain circumstances, likely related to electrode edge effects.

AbtractsApplying spatial transcriptomics (ST) to explore a vast amount of formalin-fixed paraffin-embedded (FFPE) archival cancer tissues has been highly challenging due to several critical technical issues. In this work, we optimised ST protocols to generate unprecedented spatial gene expression data for FFPE skin cancer. Skin is among the most challenging tissue types for ST due to its fibrous structure and a high risk of RNAse contamination. We evaluated tissues collected from ten years to two years ago, spanning a range of tissue qualities and complexity. Technical replicates and multiple patient samples were assessed. Further, we integrated gene expression profiles with pathological information, revealing a new layer of molecular information. Such integration is powerful in cancer research and clinical applications. The data allowed us to detect the spatial expression of non-coding RNAs. Together, this work provides important technical perspectives to enable the applications of ST on archived cancer tissues.

BackgroundThe influence of pre-existing humoral immunity, inter-individual demographic factors, and vaccine-associated reactogenicity on immunogenicity following COVID vaccination remains poorly understood.MethodsTen-fold cross-validated least absolute shrinkage and selection operator (LASSO) and linear mixed effects models were used to evaluate symptoms experienced during natural infection and following SARS-CoV-2 mRNA vaccination along with demographics as predictors for antibody (AB) responses in COVID+ participants in a longitudinal cohort study.ResultsIn previously infected individuals, AB were more durable and robust following vaccination when compared to natural infection alone. Higher AB were associated with experiencing dyspnea during natural infection, as was the total number of symptoms reported during the COVID-19 disease course. Both local and systemic symptoms following 1st and 2nd dose of SARS-CoV-2 mRNA vaccines were predictive of higher AB after vaccination, as were the demographic factors of age and Hispanic ethnicity. Lastly, there was a significant temporal relationship between AB and days since infection or vaccination.ConclusionVaccination in COVID+ individuals ensures a more robust immune response. Experiencing systemic and local symptoms post-vaccine is suggestive of higher AB, which may confer greater protection. Age and Hispanic ethnicity are predictive of higher AB.

Graphic abstract In the age of the Anthropocene, the ocean has typically been viewed as a sink for pollution. Pollution is varied, ranging from human-made plastics and pharmaceutical compounds, to human-altered abiotic factors, such as sediment and nutrient runoff. As global population, wealth and resource consumption continue to grow, so too does the amount of potential pollution produced. This presents us with a grand challenge which requires interdisciplinary knowledge to solve. There is sufficient data on the human health, social, economic, and environmental risks of marine pollution, resulting in increased awareness and motivation to address this global challenge, however a significant lag exists when implementing strategies to address this issue. This review draws upon the expertise of 17 experts from the fields of social sciences, marine science, visual arts, and Traditional and First Nations Knowledge Holders to present two futures; the Business-As-Usual, based on current trends and observations of growing marine pollution, and a More Sustainable Future, which imagines what our ocean could look like if we implemented current knowledge and technologies. We identify priority actions that governments, industry and consumers can implement at pollution sources, vectors and sinks, over the next decade to reduce marine pollution and steer us towards the More Sustainable Future. Supplementary Information The online version contains supplementary material available at 10.1007/s11160-021-09674-8.

As the United Nations develops a post-2020 global biodiversity framework for the Convention on Biological Diversity, attention is focusing on how new goals and targets for ecosystem conservation might serve its vision of ‘living in harmony with nature’1,2. Advancing dual imperatives to conserve biodiversity and sustain ecosystem services requires reliable and resilient generalizations and predictions about ecosystem responses to environmental change and management3. Ecosystems vary in their biota4, service provision5 and relative exposure to risks6, yet there is no globally consistent classification of ecosystems that reflects functional responses to change and management. This hampers progress on developing conservation targets and sustainability goals. Here we present the International Union for Conservation of Nature (IUCN) Global Ecosystem Typology, a conceptually robust, scalable, spatially explicit approach for generalizations and predictions about functions, biota, risks and management remedies across the entire biosphere. The outcome of a major cross-disciplinary collaboration, this novel framework places all of Earth’s ecosystems into a unifying theoretical context to guide the transformation of ecosystem policy and management from global to local scales. This new information infrastructure will support knowledge transfer for ecosystem-specific management and restoration, globally standardized ecosystem risk assessments, natural capital accounting and progress on the post-2020 global biodiversity framework.

Here, we present a rare case of a patient who developed multiple primary melanomas within the boundaries of two nevi depigmentosa. The melanomas were excised, and as a preventive measure, the remainder of the nevi depigmentosa were removed. We performed whole-exome sequencing on excised tissue from the nevus depigmentosus, adjacent normal skin, and saliva to explain this intriguing phenomenon. We also performed a GeneTrails Comprehensive Solid Tumor Panel analysis on one of the melanoma tissues. Genetic analysis revealed germline MC1R V92M and TYR R402Q polymorphisms and a MET E168D germline mutation that may have increased the risk of melanoma development. This genetic predisposition, combined with a patient-reported history of substantial sun exposure and sunburns, which were more severe within the boundaries of the nevi depigmentosa due to the lack of photoprotective melanin, produced numerous somatic mutations in the melanocytes of the nevi depigmentosa. Fitting with this paradigm for melanoma development in chronically sun-damaged skin, the patient's melanomas harbored somatic mutations in CDKN2A (splice site), NF1, and ATRX and had a tumor mutation burden in the 90-95th percentile for melanoma.

Background Previous work has demonstrated racial/ethnic differences in emergency department (ED) utilization, but less is known about racial/ethnic differences in the experience of care received during an ED visit. Objective To examine differences in self-reported healthcare utilization and experiences with ED care by patients’ race/ethnicity. Design Adult ED patients discharged to community (DTC) were surveyed (response rate: 20.25%) using the Emergency Department Patient Experience of Care (EDPEC) DTC Survey. Linear regression was used to estimate case-mix-adjusted differences in patient experience between racial/ethnic groups. Participants 3122 survey respondents who were discharged from the EDs of 50 hospitals nationwide January–March 2016. Main Measures Six measures: getting timely care, doctor and nurse communication, communication about medications, receipt of sufficient information about test results, whether hospital staff discussed the patient’s ability to receive follow-up care, and willingness to recommend the ED. Key Results Black and Hispanic patients were significantly more likely than White patients to report visiting the ED for an ongoing health condition (40% Black, 30% Hispanic, 28% White, p

Globally, collapse of ecosystems—potentially irreversible change to ecosystem structure, composition and function—imperils biodiversity, human health and well‐being. We examine the current state and recent trajectories of 19 ecosystems, spanning 58° of latitude across 7.7 M km2, from Australia's coral reefs to terrestrial Antarctica. Pressures from global climate change and regional human impacts, occurring as chronic ‘presses’ and/or acute ‘pulses’, drive ecosystem collapse. Ecosystem responses to 5–17 pressures were categorised as four collapse profiles—abrupt, smooth, stepped and fluctuating. The manifestation of widespread ecosystem collapse is a stark warning of the necessity to take action. We present a three‐step assessment and management framework (3As Pathway Awareness, Anticipation and Action) to aid strategic and effective mitigation to alleviate further degradation to help secure our future.

Aims: To identify potential hull fouling marine invasive species that could survive in East Antarctica presently and in the future. Location: Australia's Antarctic continental stations: Davis, Mawson and Casey, East Antarctica; and subantarctic islands: Macquarie Island and Heard and McDonald Islands. Methods: Our study uses a novel machine-learning algorithm to predict which currently known hull fouling MIS could survive in shallow benthic ecosystems adjacent to Australian Antarctic research stations and subantarctic islands, where ship traffic is present. We used gradient boosted machine learning (XGBoost) with four important environmental variables (sea surface temperature, salinity, nitrate and pH) to develop models of suitable environments for each potentially invasive species. We then used these models to determine if any of Australia's three Antarctic research stations and two subantarctic islands could be environmentally suitable for MIS now and under two future climate scenarios. Results: Most of the species were predicted to be unable to survive at any location between now and the end of this century; however, four species were identified as potential current threats and five as threats under future climate change. Asterias amurensis was identified as a potential threat to all locations. Main conclusions: This study suggests that the risks are very low, but plausible, that known hull fouling species could survive in the shallow benthic habitats near Australia's East Antarctica locations and suggest a precautionary approach is needed by way of surveillance and monitoring in this region, particularly if propagule pressure increases. While some species could survive as adults in the region, their ability to reach these locations and undergo successful reproduction is considered unlikely based on current knowledge.

Chemical spillage has been measured for undergraduate students undertaking a laboratory practical designed to help develop their chemical handling skills. There was a low correlation found between the amount of chemical spilled and the ability to accurately carry out the primary goal of the experiment, which was to measure the concentrations of samples of unknown dilution. There was also a low correlation between the amount spilled by individual students carrying out consecutive experiments, which is consistent with the proportion of spillage incidents due to personal factors (e.g., accident-prone individuals) being low. Quantitatively, only ≈6% of the spillages could be accounted for by factors relating to the individual, with a (95%) confidence interval of 0.2–23%. These observations therefore indicate that a blame culture should be avoided when dealing with chemical spillages, and also that a more effective focus for efforts to improve laboratory safety should be on organizational or workplace factors, through, for example, improving teaching methods for all students, rather than targeting specific individuals for retraining who may have had a noticeable chemical mishap. These observations also suggest that the volume of chemical spilled by a student should not be used as a measure for summative assessment, as it is a poor predictor of future spillage.

Southern Ocean waters are among the most vulnerable to ocean acidification. The projected increase in the CO2 level will cause changes in carbonate chemistry that are likely to be damaging to organisms inhabiting these waters. A meta‐analysis was undertaken to examine the vulnerability of Antarctic marine biota occupying waters south of 60°S to ocean acidification. This meta‐analysis showed that ocean acidification negatively affects autotrophic organisms, mainly phytoplankton, at CO2 levels above 1,000 μatm and invertebrates above 1,500 μatm, but positively affects bacterial abundance. The sensitivity of phytoplankton to ocean acidification was influenced by the experimental procedure used. Natural, mixed communities were more sensitive than single species in culture and showed a decline in chlorophyll a concentration, productivity, and photosynthetic health, as well as a shift in community composition at CO2 levels above 1,000 μatm. Invertebrates showed reduced fertilization rates and increased occurrence of larval abnormalities, as well as decreased calcification rates and increased shell dissolution with any increase in CO2 level above 1,500 μatm. Assessment of the vulnerability of fish and macroalgae to ocean acidification was limited by the number of studies available. Overall, this analysis indicates that many marine organisms in the Southern Ocean are likely to be susceptible to ocean acidification and thereby likely to change their contribution to ecosystem services in the future. Further studies are required to address the poor spatial coverage, lack of community or ecosystem‐level studies, and the largely unknown potential for organisms to acclimate and/or adapt to the changing conditions., Antarctic waters are among the most vulnerable in the world to ocean acidification due to their cold temperatures, naturally low levels of calcium carbonate and upwelling that brings deep CO2‐rich waters to the surface. This meta‐analysis demonstrates groups of Antarctic marine biota in waters south of 60°S have a range of tolerances to ocean acidification. Invertebrates and phytoplankton showed negative effects above 500 μatm and 1,000 μatm CO2, respectively, while bacteria appear tolerant to elevated CO2.

Understanding the distribution, abundance and habitat preferences of species in the Southern Ocean provides a foundation for assessing the impacts of environmental change and anthropogenic disturbance on Antarctic ecosystems. In near-shore waters at Casey and Davis Stations, photoquadrat surveys were used to determine sea anemone distribution and abundance, habitat preferences, associations with other species and the impact of human disturbance on sea anemone distribution. Two distinct sea anemone morphotypes were found in this study: large sea anemones that require hard substrate for attachment and small, burrowing sea anemones found in muddy sediment. The large sea anemones were found in rocky habitats, with the exception of some sedimentary habitats where other biota were used as substrate. The large sea anemones were associated with a diverse community of epibenthic species found in rocky habitats. The burrowing sea anemones were associated with a less diverse assemblage of sediment-dwelling epibenthos. At Casey Station, sea anemones were more abundant in habitats adjacent to a former waste disposal site than at control sites. The reason for this is not yet known, but may be due to high organic matter inputs or, alternatively, a longer sea ice duration providing protection from ice scour.

Objective To examine the association between prior cancer treatments, medical comorbidities, and voluntary childlessness in reproductive-age women who are survivors of cancers diagnosed as adolescents and young adults (AYA survivors). Design Cross-sectional analysis. Setting Participants were recruited from California and Texas cancer registries, fertility preservation programs, and cancer advocacy groups. Patient(s) Women (n = 413) ages 18–40 who were diagnosed with cancer between ages 15 and 35, completed primary cancer treatments, had at least one ovary, and were nulliparous. Intervention(s) Cancer treatment gonadotoxicity and medical comorbidities. Main Outcome Measure(s) Voluntary childlessness. Result(s) The mean age of survivors was 31.8 years (SD, 4.9) with a mean of 6.5 years (SD, 4.4) since cancer diagnosis. Breast (26%), thyroid (19%), and Hodgkin lymphoma (18%) were the most common cancers. Twenty-two percent of the cohort was voluntarily childless. Medical comorbidities, cancer diagnosis, prior surgery, prior chemotherapy, and prior gonadotoxic treatments were not significantly associated with voluntary childlessness. In adjusted analysis, survivors of older reproductive age (adjusted odds ratio = 2.97 [1.71–5.18]) and nonheterosexual participants (adjusted odds ratio = 4.71 [2.15–10.32]) were more likely to report voluntary childlessness. Conclusion(s) A moderate proportion of AYA cancer survivors are voluntarily childless, but reproductive intentions were not related to cancer type or cancer treatments. AYA survivors of older age and nonheterosexual identification were more likely to be voluntarily childless. These data support assessing reproductive intentions and tailoring reproductive care such as fertility and contraception counseling that is appropriate for a survivor’s intentions.

Melanomas have increased in global incidence and are the leading cause of skin cancer deaths. Whilst the majority of early-stage, non-metastatic melanomas can be cured with surgical excision alone, ~5% of patients with early melanomas will experience recurrence following a variable disease-free interval and progression to metastatic melanoma and ultimately death. This is likely because of primary tumor heterogeneity and progressive clonal divergency resulting in the growth of more aggressive tumor populations. Liquid biomarkers have the advantage of real-time, non-invasive longitudinal monitoring of tumor burden and heterogeneity over tissue markers. Currently, the only serological marker used in the staging and monitoring of melanoma is serum lactate dehydrogenase, which is not sufficiently specific or sensitive, and is not used routinely in all centers. An ideal melanoma biomarker would be used to identify patients who are at high-risk of primary melanoma, screen for relapse, detect early-stage melanoma, provide treatment outcomes to personalize systemic treatment, follow tumor heterogeneity, provide prognostic data before, during and after treatment, and monitor response to treatment. This review provides a summary of the current research in this field with a specific focus on circulating tumor cells, circulating tumor DNA, microRNA, and extracellular vesicles which may serve to suit these goals.

Melanoma may arise within a pre-existing nevus, but commonly forms in the skin adjacent to nevi. We have performed global DNA methylation profiling using the Illumina EPIC array (>800K loci) of 32 dermoscopically ('globular' vs 'non-globular' pattern) and histopathologically classified nevi, together with matching adjacent perilesional skin, and discovered that methylation patterns can accurately decompose the proportion of cell types present in the tissue. In this study, we sought to assess whether there are differences in the DNA methylation profiles of histologically normal skin samples that surround nevi, independent of cellular composition. Among the 739,270 CpG loci included in the analysis, there were a total of 8,200 CpG loci identified as significantly differentially methylated (Q < 0.05) in ‘globular skin’ vs ‘non-globular skin’ adjusted for age, sex, and the estimated relative proportions of epithelial cells, fibroblasts, and melanocytes in each sample. After imposing a more stringent threshold (M value of ≥0.5) a total 816 CpG loci were found to be DM, with 696 loci identified as significantly hypermethylated, and 120 loci significantly hypomethylated (Q < 0.05 and ΔM > 0.5) in ‘globular’ vs ‘non-globular’ skin. Mapping of the DM (Q < 0.05 and |ΔM| < 0.5) CpG loci to their respective genes revealed that eight of the top 20 DM genes, by proportion of differentially methylated loci, were positioned in proximity to suggest regulation of members of the HOX gene family. We next assessed the differential gene expression of the eight DM HOX genes in the perilesional skin as well as the matching adjacent nevus. After adjusting for age, sex, and sample cellular composition, none of the assessed HOX genes demonstrated statistically significant (P ≤ 0.05) differential expression in the nevi, however, ‘non-globular skin’ demonstrated a statistically significant (P < 0.05) increase in the expression of five of the eight HOX genes relative to ‘globular skin’. Importantly, this increased gene expression corresponds to the methylation status of the DM loci. HOX genes are known to be involved in limb and axial development as well as the positioning of dermal fibroblasts. Moreover, melanocytes from different anatomic positions have distinct transcriptional profiles and the anatomical position of melanocytes plays a key role in determining whether genetic alterations will subsequently drive melanoma formation. This positioning of melanoma subtypes (cutaneous vs acral) was recently shown to be related to interaction of specific HOX genes with site-specific oncogenic alterations. The distinct HOX gene family members we have revealed, differ to those related to melanoma development and positioning, as such we propose that these may contribute to the positioning of acquired melanocytic nevi, and in combination with common somatic alterations in BRAF, may contribute to nevus formation. Citation Format: Meghan E. Muse, Helmut Schaider, Harald Oey, H. Peter Soyer, Brock C. Christensen, Mitchell S. Stark. Distinct HOX gene family DNA methylation profiles in histologically normal skin dependent on dermoscopic pattern of adjacent nevi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6000.

Early detection of skin pathologies with current clinical diagnostic tools is challenging, particularly when there are no visible colour changes or morphological cues present on the skin. In this study, we present a terahertz (THz) imaging technology based on a narrow band quantum cascade laser (QCL) at 2.8 THz for human skin pathology detection with diffraction limited spatial resolution. THz imaging was conducted for three different groups of unstained human skin samples (benign naevus, dysplastic naevus, and melanoma) and compared to the corresponding traditional histopathologic stained images. The minimum thickness of dehydrated human skin that can provide THz contrast was determined to be 50 µm, which is approximately one half-wavelength of the THz wave used. The THz images from different types of 50 µm-thick skin samples were well correlated with the histological findings. The per-sample locations of pathology vs healthy skin can be separated from the density distribution of the corresponding pixels in the THz amplitude–phase map. The possible THz contrast mechanisms relating to the origin of image contrast in addition to water content were analyzed from these dehydrated samples. Our findings suggest that THz imaging could provide a feasible imaging modality for skin cancer detection that is beyond the visible.

Precision prevention of advanced melanoma is fast becoming a realistic prospect, with personalized, holistic risk stratification allowing patients to be directed to an appropriate level of surveillance, ranging from skin self-examinations to regular total body photography with sequential digital dermoscopic imaging. This approach aims to address both underdiagnosis (a missed or delayed melanoma diagnosis) and overdiagnosis (the diagnosis and treatment of indolent lesions that would not have caused a problem). Holistic risk stratification considers several types of melanoma risk factors: clinical phenotype, comprehensive imaging-based phenotype, familial and polygenic risks. Artificial intelligence computer-aided diagnostics combines these risk factors to produce a personalized risk score, and can also assist in assessing the digital and molecular markers of individual lesions. However, to ensure uptake and efficient use of AI systems, researchers will need to carefully consider how best to incorporate privacy and standardization requirements, and above all address consumer trust concerns.

Processing of sensory information is embedded into ongoing neural processes which contribute to brain states. Electroencephalographic microstates are semi-stable short-lived power distributions which have been associated with subsystem activity such as auditory, visual and attention networks. Here we explore changes in electrical brain states in response to an audiovisual perception and memorization task under conditions of auditory distraction. We discovered changes in brain microstates reflecting a weakening of states representing activity of the auditory system and strengthening of salience networks, supporting the idea that salience networks are active after audiovisual encoding and during memorization to protect memories and concentrate on upcoming behavioural response.

PUBLISHED IN REVIEWS IN FISH BIOLOGY AND FISHERIES: https://doi.org/10.1007/s11160-021-09674-8Kathryn A. Willis1,2,5†, Catarina S. Goncalves1,3, Kelsey Richardson1,2,5, Qamar A. Schuyler2, Halfdan Pedersen8, Kelli Anderson4, Jonathan Stark7, Joanna Vince1,5, Britta D. Hardesty2, Chris Wilcox2, Barbara Nowak4, Jennifer L. Lavers3, Jayson M. Semmens3, Dean Greeno1,6, Catriona MacLeod3, Per Ole Frederiksen (Nunnoq)9,10, Peter S. Puskic1,3*†1 Centre for Marine Sociology, University of Tasmania, Hobart, Tasmania, Australia2 CSIRO Ocean & Atmosphere, Hobart, Tasmania, Australia3 Institute for Marine and Antarctic Studies, University of Tasmania, Hobart, Tasmania, Australia4 Institute for Marine and Antarctic Studies, Fisheries and Aquaculture, University of Tasmania, Newnham, Tasmania, Australia5 School of Social Sciences, College of Arts, Law and Education, University of Tasmania, Hobart, Tasmania, Australia6 School of Creative Arts and Media, College of Arts, Law and Education, University of Tasmania, Hobart, Tasmania, Australia7 Australian Antarctic Division, Hobart, Tasmania, Australia8 Pikkoritta Consultancy, Greenland9 The PSUNA Project, Qaasuitsup Municipality, Attu, Greenland10 Snowchange Cooperative, Selkie, Finland*Corresponding Author: Peter S. Puskic (peter.puskic@utas.edu.au), Centre for Marine Sociology & Institute for Marine and Antarctic Studies; University of Tasmania, Hobart, Tasmania, Australia.† P.S. Puskic and K.A. Willis share equal lead authorship on this paper.

Antarctic benthic ecosystems support high biodiversity but their characterization is limited to a few well-studied areas, due to the extreme environment and remoteness making access and sampling difficult. Our aim was to compare water and sediment as sources of environmental DNA (eDNA) to better characterise Antarctic benthic communities and further develop practical approaches for DNA-based biodiversity assessment in remote environments. We used a cytochrome c oxidase subunit I (COI) metabarcoding approach to characterise metazoan communities in 26 nearshore sites across 12 locations in the Vestfold Hills (East Antarctica) based on DNA extracted from either sediment cores or filtered seawater. We detected a total of 99 metazoan species from 12 phyla across 26 sites, with similar numbers of species detected in sediment and water eDNA samples. However, significantly different communities were detected in the two sample types at sites where both were collected (i.e., where paired samples were available). For example, nematodes and echinoderms were more likely to be detected exclusively in sediment and water eDNA samples, respectively. eDNA from water and sediment core samples are complementary sample types, with epifauna more likely to be detected in water column samples and infauna in sediment. More reference DNA sequences are needed for infauna/meiofauna to increase the proportion of sequences and number of taxa that can be identified. Developing a better understanding of the temporal and spatial dynamics of eDNA at low temperatures would also aid interpretation of eDNA signals from polar environments. Our results provide a preliminary scan of benthic metazoan communities in the Vestfold Hills, with additional markers required to provide a comprehensive biodiversity survey. However, our study demonstrates the choice of sample type for eDNA studies of benthic ecosystems (sediment, water or both) needs to be carefully considered in light of the research or monitoring question of interest.

Ultraviolet radiation-induced DNA mutations are a primary environmental driver of melanoma. The reason for this very high level of unrepaired DNA lesions leading to these mutations is still poorly understood. The primary DNA repair mechanism for UV-induced lesions, that is, the nucleotide excision repair pathway, appears intact in most melanomas. We have previously reported a postreplication repair mechanism that is commonly defective in melanoma cell lines. Here we have used a genome-wide approach to identify the components of this postreplication repair mechanism. We have used differential transcript polysome loading to identify transcripts that are associated with UV response, and then functionally assessed these to identify novel components of this repair and cell cycle checkpoint network. We have identified multiple interaction nodes, including global genomic nucleotide excision repair and homologous recombination repair, and previously unexpected MASTL pathway, as components of the response. Finally, we have used bioinformatics to assess the contribution of dysregulated expression of these pathways to the UV signature mutation load of a large melanoma cohort. We show that dysregulation of the pathway, especially the DNA damage repair components, are significant contributors to UV mutation load, and that dysregulation of the MASTL pathway appears to be a significant contributor to high UV signature mutation load.

The authors evaluated websites offering therapeutic telehealth services (N = 55) using a 38-item checklist based on the American Psychological Association’s Guidelines for the Practice of Telepsych...

Despite the interest in MXenes in the past decade, MXenes are often highly disordered, which can complicate their study and use. For example, nearly all MXenes have a random mixture of surface term...

Short chain alkenyl succinimides (ASIs) were synthesized and used as high purity chemical models to investigate the autoxidative degradation at 170 °C of polyisobutenyl succinimide dispersants (PIB...

The ability to handle chemicals safely is a key aspect of the learning development of students studying chemistry; however, there have been no previously reported investigations of the quantity of chemicals spilled by students during lab experiments. Therefore, the first part of this article reports the assessment of the volume of chemicals spilled by year 1 undergraduate chemistry students (n = 64) at a U.K. university during an existing chemical analysis practical designed to develop volumetric handling skills. The experiment was carried out on paper liners, allowing the areas of students' spills to be visible and quantified using calibrated spill volumes of liquid to determine the resultant spill area. The volume spilled by the student group was ca. 1.2% of that handled; however, the amount spilled by individual students ranged widely, from ca. 0.02% to ca. 10% of the volume handled. A feedback tool has been developed to allow laboratory demonstrators to rapidly quantify chemical spillage by individual students. This tool also provides the demonstrators with a framework to communicate the potential safety significance of the volume of chemical a student has spilled. A randomized controlled trial (RCT) was carried out to examine the effect of providing feedback to students on their chemical spillage during a subsequent experiment. From a cohort of 185 year 1 undergraduate students, 150 consented to be randomized (81%), and data was collected for 144 students (96% of those randomized). A Hodges-Lehmann estimator for the median change in volume spilled during the second experiment due to providing feedback on spillage during first experiment was a 50% decrease in volume spilled (95% confidence range: 0 to 80% decrease, Mann-Whitney U test p = 0.05). The RCT was a waiting list trial, with all student receiving feedback either during or after the RCT, with blinded assessment by the demonstrators assessing volume spilled for the RCT.

Recent work involving survey administration among emergency department (ED) patients has demonstrated very low response rates using single-mode (e.g., mail-only or web-only) approaches. In this study, the authors tested several mixed-mode protocols that focus on a push-to-web approach for survey administration in this challenging but important setting. A random sample of 26,991 ED discharged-to-community (DTC) patients discharged in January 2018–March 2018 from 16 hospital-based EDs nationwide were randomized to nine survey arms, eight of which involved a web survey with one or more of the following methods of invitation to the web survey: an emailed link to the web survey, a texted link to the web survey, and/or a mailed paper invitation with information on how to access the web survey. The reference arm was standard mixed mode (mailed survey with telephone follow-up). Invitation(s) to the web survey was followed by (1) a mailed survey, (2) telephone follow-up, or (3) both. The overall response rate across all arms was 18.6% (American Association for Public Opinion Research [AAPOR] RR1). None of the tested web-survey arms had significantly higher response rates than standard mixed mode (25.5%). Protocol comparisons demonstrated that both text outreach and including a telephone mode increased response rates. When examining response by completion mode, the arms involving text invitation had a higher percentage of completed surveys that were completed by web than arms not involving text invitation. Characteristics (e.g., age) of telephone and web respondents were more representative of the sampled population than mail respondents. Older patients and male patients were significantly less likely to be reachable by email or text. These results demonstrate that sequential multi-mode approaches involving web, mail, and telephone with multiple methods of web survey invitation show the greatest promise for obtaining higher response rates and more representative respondents from the ED population.

Large-giant congenital melanocytic nevi have been well characterized clinically, yet questions remain about the heterogenous phenotypes observed. Martins da Silva et al. (2018) highlight the genotypic diversity between "classic" and "spilus-like" congenital melanocytic nevi by analyzing multiple biopsy sites and matching satellite nevi. This study provides evidence for alternative modes of development beyond the well-established NRAS mutation paradigm.

Kelly‐Anne S. Stark, Jason F. Alvino, K. Paul Kirkbride, Christopher J. Sumby, Gregory F. Metha, Claire E. Lenehan, Mark Fitzgerald, Craig Wall, Mark Mitchell, Chad Prior

Free Ocean CO2 Enrichment (FOCE) experiments are a relatively recent development in ocean acidification research, designed to address the need for in situ, long-term, community level experiments. FOCE studies have been conducted across different marine benthic habitats and regions, from Antarctica to the tropics. Based on this previous research we have formed some core operating principles that will aid those embarking on future FOCE experiments. FOCE studies have potential to provide important insight into the effects of ocean acidification that can add to or refine conclusions drawn from laboratory or single species studies because they are conducted in situ on intact assemblages. Scaling up from sub-organismal and individual effects to also include indirect impacts on the ecosystem and ecosystem services, make FOCE experiments essential in filling in current knowledge gaps in our understanding of ocean acidification. While FOCE systems are complex, relatively costly, and somewhat difficult to operate, the challenges they pose are tractable and they have proven to be a useful approach in ocean acidification research. The aim of this paper is to draw from the experiences of past FOCE experiments and provide practical advice for designing, building and operating a FOCE experiment. Some of the most important recommendations include: field testing the system design; having a backup power supply; using replicate treatment enclosures; monitoring and maintaining the chemistry appropriately; allowing sufficient time to achieve near CO2 equilibrium conditions; and having a scientific focus with a core set of hypotheses. Future FOCE experiments could focus on longer durations, multiple factors, and testing more intact benthic marine communities and ecosystems. We hope this paper will encourage further FOCE deployments and experiments, as well as provide some guidelines to improve future FOCE studies and advance ocean acidification research.

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieve a durable remission. Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that regulates metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we showed that SIRT5 was required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma subtype that arises in the eye and is incurable once metastatic. Likewise, SIRT5 was required for efficient tumor formation by melanoma xenografts and in an autochthonous mouse Braf Pten–driven melanoma model. Via metabolite and transcriptomic analyses, we found that SIRT5 was required to maintain histone acetylation and methylation levels in melanoma cells, thereby promoting proper gene expression. SIRT5-dependent genes notably included MITF, a key lineage-specific survival oncogene in melanoma, and the c-MYC proto-oncogene. SIRT5 may represent a druggable genotype-independent addiction in melanoma.

This work is a core contribution to the first Marine Ecosystem Assessment for the Southern Ocean (MEASO) of IMBeR’s program ICED.-- 30 pages, 8 figures, 2 tables, supplementary material https://www.frontiersin.org/articles/10.3389/fmars.2021.622721/full#supplementary-material, Knowledge of life on the Southern Ocean seafloor has substantially grown since the beginning of this century with increasing ship-based surveys and regular monitoring sites, new technologies and greatly enhanced data sharing. However, seafloor habitats and their communities exhibit high spatial variability and heterogeneity that challenges the way in which we assess the state of the Southern Ocean benthos on larger scales. The Antarctic shelf is rich in diversity compared with deeper water areas, important for storing carbon (“blue carbon”) and provides habitat for commercial fish species. In this paper, we focus on the seafloor habitats of the Antarctic shelf, which are vulnerable to drivers of change including increasing ocean temperatures, iceberg scour, sea ice melt, ocean acidification, fishing pressures, pollution and non-indigenous species. Some of the most vulnerable areas include the West Antarctic Peninsula, which is experiencing rapid regional warming and increased iceberg-scouring, subantarctic islands and tourist destinations where human activities and environmental conditions increase the potential for the establishment of non-indigenous species and active fishing areas around South Georgia, Heard and MacDonald Islands. Vulnerable species include those in areas of regional warming with low thermal tolerance, calcifying species susceptible to increasing ocean acidity as well as slow-growing habitat-forming species that can be damaged by fishing gears e.g., sponges, bryozoan, and coral species. Management regimes can protect seafloor habitats and key species from fishing activities; some areas will need more protection than others, accounting for specific traits that make species vulnerable, slow growing and long-lived species, restricted locations with optimum physiological conditions and available food, and restricted distributions of rare species. Ecosystem-based management practices and long-term, highly protected areas may be the most effective tools in the preservation of vulnerable seafloor habitats. Here, we focus on outlining seafloor responses to drivers of change observed to date and projections for the future. We discuss the need for action to preserve seafloor habitats under climate change, fishing pressures and other anthropogenic impacts, MB was supported by the Antarctic Climate & Ecosystems Cooperative Research Centre and PEW Charitable Trusts. RD was funded by an Australian Government Research Training Program (AGRTP). SM and HG were funded through NERC core funding to the British Antarctic Survey Biodiversity, Evolution and Adaptation Team. BF was supported by a postdoctoral contract Juan de la Cierva-Incorporación (IJCI-2017-31478) of Ministerio de Ciencia, Innovación y Universidades. AV was funded by the Belgian Science Policy Office (BELSPO, contract n° FR/36/AN1/AntaBIS) in the Framework of EU-Lifewatch. [...] BF received institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

Author(s): Chen, Peggy G; Tolpadi, Anagha; Elliott, Marc N; Hays, Ron D; Lehrman, William G; Stark, Debra S; Parast, Layla

Acquired melanocytic nevi grow and persist in a stable form into adulthood. Using genome-wide methylation profiling, we evaluated 32 histopathologically and dermoscopically characterized nevi to identify the key epigenetic regulatory mechanisms involved in nevogenesis. Benign (69% globular and 31% nonspecific dermoscopic pattern) and dysplastic (95% reticular/nonspecific dermoscopic pattern) nevi were dissimilar, with only two shared differentially methylated loci. Benign nevi showed an increase in both genome-scale methylation and methylation of Alu/LINE-1 retrotransposable elements, a marker of genomic stability, as well as global methylation. In contrast, dysplastic nevi showed evidence for genomic instability through the hypomethylation of Alu/LINE-1 (Alu: P = 0.00019; LINE-1: P = 0.000035). Using dermoscopic classifications, reticular/nonspecific patterned nevi had 59,572 5'-C-phosphate-G-3' differentially methylated loci (Q0.05), whereas globular nevi had no significant differentially methylated loci. In reticular/nonspecific patterned nevi, the tumor suppressor PTEN had the greatest proportion of hypermethylated 5'-C-phosphate-G-3' loci in its promoter region than all other assayed gene promoters. The relative activity of reticular/nonspecific nevi was evidenced by 50,720 hypomethylated loci being enriched for accessible chromatin and 8,852 hypermethylated loci strongly enriched, for example, marks of active gene promoters, which suggests that gain of DNA methylation observed in these nevus types plays a role in gene regulation.

Understanding the vulnerability of marine calcifiers to ocean acidification is a critical issue, especially in the Southern Ocean (SO), which is likely to be the one of the first, and most severely affected regions. Since the industrial revolution, ~30% of anthropogenic CO2 has been absorbed by the global oceans. Average surface seawater pH levels have already decreased by 0.1 and are projected to decline by ~0.3 by the year 2100. This process, known as ocean acidification (OA), is shallowing the saturation horizon, which is the depth below which calcium carbonate (CaCO3) dissolves, likely increasing the vulnerability of many resident marine calcifiers to dissolution. The negative impact of OA may be seen first in species depositing more soluble CaCO3 mineral phases such as aragonite and high-Mg calcite (HMC). Ocean warming could further exacerbate the effects of OA in these particular species. Here we combine a review and a quantitative meta-analysis to provide an overview of the current state of knowledge about skeletal mineralogy of major taxonomic groups of SO marine calcifiers and to make projections about how OA might affect a broad range of SO taxa. We consider a species' geographic range, skeletal mineralogy, biological traits, and potential strategies to overcome OA. The meta-analysis of studies investigating the effects of the OA on a range of biological responses such as shell state, development and growth rate illustrates that the response variation is largely dependent on mineralogical composition. Species-specific responses due to mineralogical composition indicate that taxa with calcitic, aragonitic, and HMC skeletons, could be at greater risk to expected future carbonate chemistry alterations, and low-Mg calcite (LMC) species could be mostly resilient to these changes. Environmental and biological control on the calcification process and/or Mg content in calcite, biological traits, and physiological processes are also expected to influence species-specific responses.

Diminishing prospects for environmental preservation under climate change are intensifying efforts to boost capture, storage and sequestration (long-term burial) of carbon. However, as Earth's biological carbon sinks also shrink, remediation has become a key part of the narrative for terrestrial ecosystems. In contrast, blue carbon on polar continental shelves have stronger pathways to sequestration and have increased with climate-forced marine ice losses-becoming the largest known natural negative feedback on climate change. Here we explore the size and complex dynamics of blue carbon gains with spatiotemporal changes in sea ice (60-100 MtCyear

Diminishing prospects for environmental preservation under climate change are intensifying efforts to boost capture, storage and sequestration (long-term burial) of carbon. However, as Earth’s biological carbon sinks also shrink, remediation has become a key part of the narrative for terrestrial ecosystems. In contrast, blue carbon on polar continental shelves have stronger pathways to sequestration and have increased with climate-forced marine ice losses—becoming the largest known natural negative feedback on climate change. Here we explore the size and complex dynamics of blue carbon gains with spatiotemporal changes in sea ice (60–100 MtCyear−1), ice shelves (4–40 MtCyear−1 = giant iceberg generation) and glacier retreat (−1). Estimates suggest that, amongst these, reduced duration of seasonal sea ice is most important. Decreasing sea ice extent drives longer (not necessarily larger biomass) smaller cell-sized phytoplankton blooms, increasing growth of many primary consumers and benthic carbon storage—where sequestration chances are maximal. However, sea ice losses also create positive feedbacks in shallow waters through increased iceberg movement and scouring of benthos. Unlike loss of sea ice, which enhances existing sinks, ice shelf losses generate brand new carbon sinks both where giant icebergs were, and in their wake. These also generate small positive feedbacks from scouring, minimised by repeat scouring at biodiversity hotspots. Blue carbon change from glacier retreat has been least well quantified, and although emerging fjords are small areas, they have high storage-sequestration conversion efficiencies, whilst blue carbon in polar waters faces many diverse and complex stressors. The identity of these are known (e.g. fishing, warming, ocean acidification, non-indigenous species and plastic pollution) but not their magnitude of impact. In order to mediate multiple stressors, research should focus on wider verification of blue carbon gains, projecting future change, and the broader environmental and economic benefits to safeguard blue carbon ecosystems through law.

Benign naevi are closely linked to melanoma, as risk factors, simulators, or sites of melanoma formation. There is a heavy genetic overlap between the two lesions, a shared environmental influence of ultraviolet radiation, and many similar cellular features, yet naevi remain locally situated while melanomas spread from their primary site and may progress systemically to distal organs. Untangling the overlapping contributors and predictors of naevi and melanoma is an ongoing area of research and should eventually lead to more personalized prevention and treatment strategies, through the development of melanoma risk stratification tools and early detection of evolving melanomas. This will be achieved through a range of complementary strategies: risk-adjusted primary prevention counseling; the use of lesion imaging technologies such as sequential 3D total body photography and consumer-performed lesion imaging; artificial intelligence deep phenotyping and clinical assistance; a better understanding of genetic drivers of malignancy, risk variants, clinical genetics, and polygenic effects; and the interplay between genetics, phenotype and the environment.

Understanding the vulnerability of marine calcifiers to ocean acidification is a critical issue, especially in the Southern Ocean (SO), which is likely to be the one of the first, and most severely affected regions. Since the industrial revolution, ~30% of anthropogenic CO2 has been absorbed by the oceans. Seawater pH levels have already decreased by 0.1 and are predicted to decline by ~ 0.3 by the year 2100. This process, known as ocean acidification (OA), is shallowing the saturation horizon, which is the depth below which calcium carbonate (CaCO3) dissolves, likely increasing the vulnerability of many marine calcifiers to dissolution. The negative impact of OA may be seen first in species depositing more soluble CaCO3 mineral phases such as aragonite and high-Mg calcite (HMC). These negative effects may become even exacerbated by increasing sea temperatures. Here we combine a review and a quantitative meta-analysis to provide an overview of the current state of knowledge about skeletal mineralogy of major taxonomic groups of SO marine calcifiers and to make predictions about how OA might affect different taxa. We consider their geographic range, skeletal mineralogy, biological traits and potential strategies to overcome OA. The meta-analysis of studies investigating the effects of the OA on a range of biological responses such as shell state, development and growth rate shows response variation depending on mineralogical composition. Species-specific responses due to mineralogical composition suggest taxa with calcitic, aragonitic and HMC skeletons may be more vulnerable to the expected carbonate chemistry alterations, and low magnesium calcite (LMC) species may be mostly resilient. Environmental and biological control on the calcification process and/or Mg content in calcite, biological traits and physiological processes are also expected to influence species specific responses.

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieves a durable remission. SIRT5 is a member of the sirtuin family of protein deacylases that regulate metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we show that SIRT5 is required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma subtype that arises in the eye and is incurable once metastatic. Likewise, SIRT5 is required for efficient tumor formation by melanoma xenografts and in an autochthonous mouse Braf;Pten-driven melanoma model. Via metabolite and transcriptomic analyses, we find that SIRT5 is required to maintain histone acetylation and methylation levels in melanoma cells, thereby promoting proper gene expression. SIRT5-dependent genes notably include MITF, a key lineage-specific survival oncogene in melanoma, and the c-MYC proto-oncogene. SIRT5 may represent a novel, druggable genotype-independent addiction in melanoma.

IMPORTANCE: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care. OBJECTIVE: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies. EVIDENCE REVIEW: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed. FINDINGS: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility. CONCLUSIONS AND RELEVANCE: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.