Expression of the Insulin-like Growth Factor system in first and second trimester human embryonic and fetal gonads

Financial Support: This work was supported by The Medical Research Council [MR/L010011/1 to PAF] and the European Community's Seventh Framework Programme (FP7/2007-2013) [under grant agreement no 212885 to PAF], BBSRC/EASTBIO (to AZ), ESHRE supported the ReproUnion fellowship (to AZ), Rigshospitalets Forskningspuljer (to LSM), and ReproUnion 1.0 (to LSM). Acknowledgement Marianne Sguazzino is acknowledged for excellent technical assistance. Gabriela Gudbergsen is acknowledged for her excellent design of Fig. 1. Data Availability: The dataset generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request. Microarray data are available with the Array Express accession number: E-MTAB-5611Peer reviewedPostprin

Taking Stock of Circumboreal Forest Carbon With Ground Measurements, Airborne and Spaceborne LiDAR

The boreal forest accounts for one-third of global forests, but remains largely inaccessible to ground-based measurements and monitoring. It contains large quantities of carbon in its vegetation and soils, and research suggests that it will be subject to increasingly severe climate-driven disturbance. We employ a suite of ground-, airborne- and space-based measurement techniques to derive the first satellite LiDAR-based estimates of aboveground carbon for the entire circumboreal forest biome. Incorporating these inventory techniques with uncertainty analysis, we estimate total aboveground carbon of 38 +/- 3.1 Pg. This boreal forest carbon is mostly concentrated from 50 to 55degN in eastern Canada and from 55 to 60degN in eastern Eurasia. Both of these regions are expected to warm >3 C by 2100, and monitoring the effects of warming on these stocks is important to understanding its future carbon balance. Our maps establish a baseline for future quantification of circumboreal carbon and the described technique should provide a robust method for future monitoring of the spatial and temporal changes of the aboveground carbon content

Statistical properties of hybrid estimators proposed for GEDI – NASA’s Global Ecosystem Dynamics Investigation

NASA’s Global Ecosystem Dynamics Investigation (GEDI) mission will collect waveform lidar data at a dense sample of ∼25 m footprints along ground tracks paralleling the orbit of the International Space Station (ISS). GEDI’s primary science deliverable will be a 1 km grid of estimated mean aboveground biomass density (Mg ha ^−1 ), covering the latitudes overflown by ISS (51.6 °S to 51.6 °N). One option for using the sample of waveforms contained within an individual grid cell to produce an estimate for that cell is hybrid inference, which explicitly incorporates both sampling design and model parameter covariance into estimates of variance around the population mean. We explored statistical properties of hybrid estimators applied in the context of GEDI, using simulations calibrated with lidar and field data from six diverse sites across the United States. We found hybrid estimators of mean biomass to be unbiased and the corresponding estimators of variance appeared to be asymptotically unbiased, with under-estimation of variance by approximately 20% when data from only two clusters (footprint tracks) were available. In our study areas, sampling error contributed more to overall estimates of variance than variability due to the model, and it was the design-based component of the variance that was the source of the variance estimator bias at small sample sizes. These results highlight the importance of maximizing GEDI’s sample size in making precise biomass estimates. Given a set of assumptions discussed here, hybrid inference provides a viable framework for estimating biomass at the scale of a 1 km grid cell while formally accounting for both variability due to the model and sampling error

Holocene deglaciation drove rapid genetic diversification of Atlantic walrus

Rapid global warming is severely impacting Arctic ecosystems and is predicted to transform the abundance, distribution and genetic diversity of Arctic species, though these linkages are poorly understood. We address this gap in knowledge using palaeogenomics to examine how earlier periods of global warming influenced the genetic diversity of Atlantic walrus (Odobenus rosmarus rosmarus), a species closely associated with sea ice and shallow-water habitats. We analysed 82 ancient and historical Atlantic walrus mitochondrial genomes (mitogenomes), including now-extinct populations in Iceland and the Canadian Maritimes, to reconstruct the Atlantic walrus' response to Arctic deglaciation. Our results demonstrate that the phylogeography and genetic diversity of Atlantic walrus populations was initially shaped by the last glacial maximum (LGM), surviving in distinct glacial refugia, and subsequently expanding rapidly in multiple migration waves during the late Pleistocene and early Holocene. The timing of diversification and establishment of distinct populations corresponds closely with the chronology of the glacial retreat, pointing to a strong link between walrus phylogeography and sea ice. Our results indicate that accelerated ice loss in the modern Arctic may trigger further dispersal events, likely increasing the connectivity of northern stocks while isolating more southerly stocks putatively caught in small pockets of suitable habitat

Scoping workshop 3 on next generation of mixed fisheries advice (WKMIXFISH3)

WKMIXFISH are a series of workshops bringing together scientists, advice recipients, and stakeholders to identify future research and advisory priorities for mixed fisheries science. The third scoping workshop on the next generation of mixed fisheries advice (WKMIXFISH3) met to review changes to mixed fisheries considerations and progress on method development since the last workshop in March 2023. The workshop focused on three areas of development. First, it reviewed changes and clarifications to mixed fisheries considerations that were incorporated to improve communication around the purpose of and assumptions in the advice. Second, it reviewed the substantial methodological development that has been undertaken by WGMIXFISH-METHODS and EU and UK research projects. The focus of this work was to address an EU/UK joint request to ICES on mixed fisheries science. Third, it discussed the outcome of a workshop on fleet and métier definitions (WKMIXFLEET) that took place the preceding two days. Methodological developments included evaluation of uncertainty in mixed fisheries models, analyses of sensitivity to model assumptions, including fleet and métier structure, and creating new ways to explore mixed fisheries data. It was noted that these, in combination with new tools, guidance, and visualizations, helped to provide greater understanding of the models and advice. While these endeavours are ongoing, there was general support for continued development; in particular, the deployment of a mixed fisheries online app to provide end-users and stakeholders with the ability to interact with the multifaceted outputs from mixed fisheries models. Support for, and engagement with, developments on using the Regional Database Estimation System (RDBES) data to make improvements to fleet and métier definitions was also highlighted. Next steps identified were for WGMIXFISH-ADVICE and WGMIXFISH-METHODS to use the valuable feedback obtained to continue to develop the tools, and implement and receive feedback on them as part of an iterative process. It was noted that further research and dedicated time for scientists was necessary to support the ongoing improvements to mixed fisheries advice and data products, and that this should be a priority.info:eu-repo/semantics/publishedVersio

Expression of Androgen Receptor Splice Variants in Prostate Cancer Bone Metastases is Associated with Castration-Resistance and Short Survival

Background: Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote  the development of castration-resistant prostate cancer (CRPC). The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN) and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival. Methodology/Principal Findings: Hormone-naı¨ve (n = 10) and CRPC bone metastases samples (n = 30) were obtained from  40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl) and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival. Conclusions/Significance: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis

Adverse cardiovascular events and mortality in men during testosterone treatment : an individual patient and aggregate data meta-analysis

Funding National Institute for Health Research Health Technology Assessment Programme. Acknowledgments This work was supported by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme (project no 17/68/01). The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR HTA Programme, or the Department of Health and Social Care, UK. The funders were not actively involved in the research process at any stage. The study design; collection, analysis, and interpretation of data; writing of the manuscript; and decision to submit for publication were performed independent of the funders. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. The following authors are also funded as follows: NIHR Research Professorship (WSD), NIHR post-doctoral fellowship (CNJ). SBhasin receives National Institutes of Health research grant funding. The authors are grateful to Prakash Abraham, Alison Avenell, Craig Ramsay, Graham Scotland, Neil Scott, and Finlay MacKenzie for their advice; and to the many individuals from academia and industry who helped in the conduct of this study.Peer reviewedPublisher PD