Observations of shallow methane bubble emissions from Cascadia Margin

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Michel, A. P. M., Preston, V. L., Fauria, K. E., & Nicholson, D. P. Observations of shallow methane bubble emissions from Cascadia Margin. Frontiers in Earth Science, 9, (2021): 613234, https://doi.org/10.3389/feart.2021.613234.Open questions exist about whether methane emitted from active seafloor seeps reaches the surface ocean to be subsequently ventilated to the atmosphere. Water depth variability, coupled with the transient nature of methane bubble plumes, adds complexity to examining these questions. Little data exist which trace methane transport from release at a seep into the water column. Here, we demonstrate a coupled technological approach for examining methane transport, combining multibeam sonar, a field-portable laser-based spectrometer, and the ChemYak, a robotic surface kayak, at two shallow (<75 m depth) seep sites on the Cascadia Margin. We demonstrate the presence of elevated methane (above the methane equilibration concentration with the atmosphere) throughout the water column. We observe areas of elevated dissolved methane at the surface, suggesting that at these shallow seep sites, methane is reaching the air-sea interface and is being emitted to the atmosphere.Funding for VP was provided by an NDSEG Fellowship. Funding for KF was provided by a WHOI Postdoctoral Scholar Fellowship. Ship time on the R/V Falkor was provided by the Schmidt Ocean Institute (FK180824)

Research methods of Talking About The Smokes: an International Tobacco Control Policy Evaluation Project study with Aboriginal and Torres Strait Islander Australians

Objective: To describe the research methods and baseline sample of the Talking About The Smokes (TATS) project.Design: The TATS project is a collaboration between research institutions and Aboriginal community-controlled health services (ACCHSs) and their state and national representative bodies. It is one of the studies within the International Tobacco Control Policy Evaluation Project, enabling national and international comparisons. It includes a prospective longitudinal study of Aboriginal and Torres Strait Islander smokers and recent ex-smokers; a survey of non-smokers; repeated cross-sectional surveys of ACCHS staff; and descriptions of the tobacco policies and practices at the ACCHSs. Community members completed face-to-face surveys; staff completed surveys on paper or online. We compared potential biases and the distribution of variables common to the main community baseline sample and unweighted and weighted results of the 2008 National Aboriginal and Torres Strait Islander Social Survey (NATSISS). The baseline survey (Wave 1) was conducted between April 2012 and October 2013.Setting and participants: 2522 Aboriginal and Torres Strait Islander people in 35 locations (the communities served by 34 ACCHSs and one community in the Torres Strait), and 645 staff in the ACCHSs.Main outcome measures: Sociodemographic and general health indicators, smoking status, number of cigarettes smoked per day and quit attempts.Results: The main community baseline sample closely matched the distribution of the Aboriginal and Torres Strait Islander population in the weighted NATSISS by age, sex, jurisdiction and remoteness. There were inconsistent differences in some sociodemographic factors between our sample and the NATSISS: our sample had higher proportions of unemployed people, but also higher proportions who had completed Year 12 and who lived in more advantaged areas. In both surveys, similar percentages of smokers reported having attempted to quit in the past year, and daily smokers reported similar numbers of cigarettes smoked per day.Conclusion: The TATS project provides a detailed and nationally representative description of Aboriginal and Torres Strait Islander smoking behaviour, attitudes, knowledge and exposure to tobacco control activities and policies, and their association with quitting

Impact of Post-incarceration Care Engagement interventions On Hiv Transmission among Young Black Men Who Have Sex With Men and their Sexual Partners: an agent-Based Network Modeling Study

BACKGROUND: Understanding the impact of incarceration on HIV transmission among Black men who have sex with men is important given their disproportionate representation among people experiencing incarceration and the potential impact of incarceration on social and sexual networks, employment, housing, and medical care. We developed an agent-based network model (ABNM) of 10,000 agents representing young Black men who have sex with men in the city of Chicago to examine the impact of varying degrees of post-incarceration care disruption and care engagement interventions following release from jail on HIV incidence. METHODS: Exponential random graph models were used to model network formation and dissolution dynamics, and network dynamics and HIV care continuum engagement were varied according to incarceration status. Hypothetical interventions to improve post-release engagement in HIV care for individuals with incarceration (e.g., enhanced case management, linkage to housing and employment services) were compared to a control scenario with no change in HIV care engagement after release. FINDING: HIV incidence at 10 years was 4.98 [95% simulation interval (SI): 4.87, 5.09 per 100 person-years (py)] in the model population overall; 5.58 (95% SI 5.38, 5.76 per 100 py) among those with history of incarceration, and 12.86 (95% SI 11.89, 13.73 per 100 py) among partners of agents recently released from incarceration. Sustained post-release HIV care for agents with HIV and experiencing recent incarceration resulted in a 46% reduction in HIV incidence among post-incarceration partners [incidence rate (IR) per 100 py = 5.72 (95% SI 5.19, 6.27) vs. 10.61 (95% SI 10.09, 11.24); incidence rate ratio (IRR) = 0.54; (95% SI 0.48, 0.60)] and a 19% reduction in HIV incidence in the population overall [(IR per 100 py = 3.89 (95% SI 3.81-3.99) vs. 4.83 (95% SI 4.73, 4.92); IRR = 0.81 (95% SI 0.78, 0.83)] compared to a scenario with no change in HIV care engagement from pre-to post-release. INTERPRETATION: Developing effective and scalable interventions to increase HIV care engagement among individuals experiencing recent incarceration and their sexual partners is needed to reduce HIV transmission among Black men who have sex with men. FUNDING: This work was supported by the following grants from the National Institutes of Health: R01DA039934; P20 GM 130414; P30 AI 042853; P30MH058107; T32 DA 043469; U2C DA050098 and the California HIV/AIDS Research Program: OS17-LA-003; H21PC3466

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands. Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry. Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell. Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus

Fixation and Spread of Somatic Mutations in Adult Human Colonic Epithelium.

We investigated the means and timing by which mutations become fixed in the human colonic epithelium by visualizing somatic clones and mathematical inference. Fixation requires two sequential steps. First, one of approximately seven active stem cells residing within each colonic crypt has to be mutated. Second, the mutated stem cell has to replace neighbors to populate the entire crypt in a process that takes several years. Subsequent clonal expansion due to crypt fission is infrequent for neutral mutations (around 0.7% of all crypts undergo fission in a single year). Pro-oncogenic mutations subvert both stem cell replacement to accelerate fixation and clonal expansion by crypt fission to achieve high mutant allele frequencies with age. The benchmarking of these behaviors allows the advantage associated with different gene-specific mutations to be compared irrespective of the cellular mechanisms by which they are conferred

Signatures of TOP1 transcription-associated mutagenesis in cancer and germline

The mutational landscape is shaped by many processes. Genic regions are vulnerable to mutation but are preferentially protected by transcription-coupled repair1. In microorganisms, transcription has been demonstrated to be mutagenic2,3; however, the impact of transcription-associated mutagenesis remains to be established in higher eukaryotes4. Here we show that ID4—a cancer insertion–deletion (indel) mutation signature of unknown aetiology5 characterized by short (2 to 5 base pair) deletions —is due to a transcription-associated mutagenesis process. We demonstrate that defective ribonucleotide excision repair in mammals is associated with the ID4 signature, with mutations occurring at a TNT sequence motif, implicating topoisomerase 1 (TOP1) activity at sites of genome-embedded ribonucleotides as a mechanistic basis. Such TOP1-mediated deletions occur somatically in cancer, and the ID-TOP1 signature is also found in physiological settings, contributing to genic de novo indel mutations in the germline. Thus, although topoisomerases protect against genome instability by relieving topological stress6, their activity may also be an important source of mutations in the human genome.We thank S. Jinks-Robertson for suggesting the traffic light reporter approach; H. Klein for guidance on fluctuation assays; R. van Boxtel for sharing sequencing data for MLH1-KO organoids; A. Bretherick, O. B. Reina and G. Kudla for advice on HygroR re-coding; staff at the IGC core services (L. Murphy, C. Nicol, C. Warnock, E. Freyer, S. Brown and J. Joseph), C. Logan, A. Fluteau, A. Robertson and the staff at Edinburgh Genomics for technical assistance; staff at Liverpool CLL Biobank (funded by Blood Cancer UK) for samples used to generate GEL WGS data; A. Ewing, C.-A. Martin, N. Hastie and W. Bickmore for discussions. Funding for this work: UK Medical Research Council Human Genetics Unit core grants (MC_UU_00007/5 to A.P.J., MC_UU_00007/11 to M.S.T.); Edinburgh Clinical Academic Track PhD programme (Wellcome Trust 204802/Z/16/Z) to T.C.W.; 2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research (grant number 21-40-11-NADE) to F.N.; a CRUK Brain Tumour Centre of Excellence Award (C157/A27589) to M.D.N.; EKFS research grant (2019_A09), Wilhelm Sander-Stiftung (2019.046.1) to K.A., CRUK programme grant (C20807/A2864) to T.S.; La Caixa Foundation (CLLEvolution-LCF/PR/HR17/52150017, Health Research 2017 Program HR17-00221) to E.C.; E.C. is an Academia Researcher of the Institució Catalana de Recerca i Estudis Avançats of the Generalitat de Catalunya. Edinburgh Genomics is partly supported by NERC (R8/H10/56), MRC (MR/K001744/1) and BBSRC (BB/J004243/1). This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support.Peer Reviewed"Article signat per 22 autors/es: Martin A. M. Reijns, David A. Parry, Thomas C. Williams, Ferran Nadeu, Rebecca L. Hindshaw, Diana O. Rios Szwed, Michael D. Nicholson, Paula Carroll, Shelagh Boyle, Romina Royo, Alex J. Cornish, Hang Xiang, Kate Ridout, The Genomics England Research Consortium, Colorectal Cancer Domain UK 100,000 Genomes Project, Anna Schuh, Konrad Aden, Claire Palles, Elias Campo, Tatjana Stankovic, Martin S. Taylor & Andrew P. Jackson "Postprint (published version

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Background & Aims The existence of slowly cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients. Methods Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg/m2 body surface area; maximum dose, 400 mg) over a 30-minute period; the IdU had a circulation half-life of 8 hours. Tissues were collected at 7, 11, 29, and 67 days after infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. Results No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this time point. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine). Conclusions LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia, is required

Trio of super-Earth candidates orbiting K-dwarf HD 48948:a new habitable zone candidate

We present the discovery of three super-Earth candidates orbiting HD 48948, a bright K-dwarf star with an apparent magnitude of mv = 8.58 mag. As part of the HARPS-N Rocky Planet Search programme, we collect 189 high-precision radial velocity measurements using the HARPS-N spectrograph from 2013 October 6, to 2023 April 16. Various methodologies are applied to extract the radial velocities from the spectra, and we conduct a comprehensive comparative analysis of the outcomes obtained through these diverse extraction techniques. To ensure the robustness of our findings, we employ several methods to address stellar variability, with a focus on Gaussian Process regression. To account for the impact of stellar variability and correlated noise in the radial velocity data set, we include activity indicators, such as logR'HK and bisector span, in the multidimensional Gaussian Process regression. Our analysis reveals three planetary candidates with orbital periods of 7.3, 38, and 151 d, and minimum masses estimated at 4.88 ± 0.21 M⊕, 7.27 ± 0.70 M⊕, and 10.59 ± 1.00 M⊕, respectively. The outermost planet resides within the (temperate) habitable zone, positioned at a projected distance of 0.029 arcsec from its star. Given the close proximity of this planetary system, situated at a distance of 16.8 parsecs, HD 48498 emerges as a promising target (closest super-Earth around FGK stars) for future high-contrast direct imaging and high-resolution spectroscopic studie

Trio of super-Earth candidates orbiting K-dwarf HD 48948:a new habitable zone candidate

We present the discovery of three super-Earth candidates orbiting HD 48948, a bright K-dwarf star with an apparent magnitude of mv = 8.58 mag. As part of the HARPS-N Rocky Planet Search programme, we collect 189 high-precision radial velocity measurements using the HARPS-N spectrograph from 2013 October 6, to 2023 April 16. Various methodologies are applied to extract the radial velocities from the spectra, and we conduct a comprehensive comparative analysis of the outcomes obtained through these diverse extraction techniques. To ensure the robustness of our findings, we employ several methods to address stellar variability, with a focus on Gaussian Process regression. To account for the impact of stellar variability and correlated noise in the radial velocity data set, we include activity indicators, such as logR'HK and bisector span, in the multidimensional Gaussian Process regression. Our analysis reveals three planetary candidates with orbital periods of 7.3, 38, and 151 d, and minimum masses estimated at 4.88 ± 0.21 M⊕, 7.27 ± 0.70 M⊕, and 10.59 ± 1.00 M⊕, respectively. The outermost planet resides within the (temperate) habitable zone, positioned at a projected distance of 0.029 arcsec from its star. Given the close proximity of this planetary system, situated at a distance of 16.8 parsecs, HD 48498 emerges as a promising target (closest super-Earth around FGK stars) for future high-contrast direct imaging and high-resolution spectroscopic studie

Trio of super-Earth candidates orbiting K-dwarf HD 48948 : a new habitable zone candidate

Funding: SD acknowledges support from the STFC consolidated grant no. ST/V000721/1. FR is funded by the University of Exeter’s College of Engineering, Maths and Physical Sciences, UK. ACC acknowledges support from STFC consolidated grant numbers ST/R000824/1 and ST/V000861/1, and UKSA grant no. ST/R003203/1. KR is grateful for support from UK STFC via consolidated grant no. ST/V000594/1. RDH is funded by the UK Science and Technology Facilities Council (STFC)’s Ernest Rutherford Fellowship (grant number ST/V004735/1). MC acknowledges the SNSF support under grant P500PT 211024. AS, ASB, and MD gratefully acknowledge support from the ‘Programma di Ricerca Fondamentale INAF 2023’ of the National Institute of Astrophysics (Large Grant 2023 EXODEMO). MP acknowledges support from the Italian Space Agency (ASI) under contract 2018-24-HH.0 ‘The Italian participation to the Gaia Data Processing and Analysis Consortium (DPAC)’ in collaboration with the Italian National Institute of Astrophysics. MP also acknowledges support from the European Union – NextGenerationEU (PRIN MUR 2022 20229R43BH) and the ‘Programma di Ricerca Fondamentale INAF 2023’. FPE and CLO would like to acknowledge the Swiss National Science Foundation (SNSF) for supporting research with HARPS-N through the SNSF grant numbers 140649, 152721, 166227, 184618, and 215190.We present the discovery of three super-Earth candidates orbiting HD 48948, a bright K-dwarf star with an apparent magnitude of mV = 8.58 mag. As part of the HARPS-N Rocky Planet Search programme, we collect 189 high-precision radial velocity measurements using the HARPS-N spectrograph from 2013 October 6, to 2023 April 16. Various methodologies are applied to extract the radial velocities from the spectra, and we conduct a comprehensive comparative analysis of the outcomes obtained through these diverse extraction techniques. To ensure the robustness of our findings, we employ several methods to address stellar variability, with a focus on Gaussian Process regression. To account for the impact of stellar variability and correlated noise in the radial velocity data set, we include activity indicators, such as logR′HK and bisector span, in the multidimensional Gaussian Process regression. Our analysis reveals three planetary candidates with orbital periods of 7.3, 38, and 151 d, and minimum masses estimated at 4.88±0.21 M ⊕ , 7.27±0.70 M ⊕ , and 10.59±1.00 M ⊕ , respectively. The outermost planet resides within the (temperate) habitable zone, positioned at a projected distance of 0.029arcsec from its star. Given the close proximity of this planetary system, situated at a distance of 16.8 parsecs, HD 48498 emerges as a promising target (closest super-Earth around FGK stars) for future high-contrast direct imaging and high-resolution spectroscopic studies.Peer reviewe