3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action

Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources

3,5-T2-A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action.

Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources

3,5-T2-A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action.

Over the last decades, thyroid hormone metabolites (THMs) received marked attention as it has been demonstrated that they are bioactive compounds. Their concentrations were determined by immunoassay or mass-spectrometry methods. Among those metabolites, 3,5-diiodothyronine (3,5-T2), occurs at low nanomolar concentrations in human serum, but might reach tissue concentrations similar to those of T4 and T3, at least based on data from rodent models. However, the immunoassay-based measurements in human sera revealed remarkable variations depending on antibodies used in the assays and thus need to be interpreted with caution. In clinical experimental approaches in euthyroid volunteers and hypothyroid patients using the immunoassay as the analytical tool no evidence of formation of 3,5-T2 from its putative precursors T4 or T3 was found, nor was any support found for the assumption that 3,5-T2 might represent a direct precursor for serum 3-T1-AM generated by combined deiodination and decarboxylation from 3,5-T2, as previously documented for mouse intestinal mucosa. We hypothesized that lowered endogenous production of 3,5-T2 in patients requiring T4 replacement therapy after thyroidectomy or for treatment of autoimmune thyroid disease, compared to production of 3,5-T2 in individuals with intact thyroid glands might contribute to the discontent seen in a subset of patients with this therapeutic regimen. So far, our observations do not support this assumption. However, the unexpected association between high serum 3,5-T2 and elevated urinary concentrations of metabolites related to coffee consumption requires further studies for an explanation. Elevated 3,5-T2 serum concentrations were found in several situations including impaired renal function, chronic dialysis, sepsis, non-survival in the ICU as well as post-operative atrial fibrillation (POAF) in studies using a monoclonal antibody-based chemoluminescence immunoassay. Pilot analysis of human sera using LC-linear-ion-trap-mass-spectrometry yielded 3,5-T2 concentrations below the limit of quantification in the majority of cases, thus the divergent results of both methods need to be reconciliated by further studies. Although positive anti-steatotic effects have been observed in rodent models, use of 3,5-T2 as a muscle anabolic, slimming or fitness drug, easily obtained without medical prescription, must be advised against, considering its potency in suppressing the HPT axis and causing adverse cardiac side effects. 3,5-T2 escapes regular detection by commercially available clinical routine assays used for thyroid function tests, which may be seriously disrupted in individuals self-administering 3,5-T2 obtained over-the counter or from other sources

The value and opportunities of community-and citizen-based approaches to tropical forest biodiversity monitoring

The biodiversity sourcebook is accessible in pdf format for free from:•GOFC-GOLD Land Cover Office website: http://www.gofcgold.wur.nl/sites/gofcgold-geobon_biodiversitysourcebook.php•GEO BON website:http://geobon.org

Corrigendum to “Environmental and life-history factors influence inter-colony multidimensional niche metrics of a breeding Arctic marine bird” [Sci. Total Environ. 796 (2021) 148935] (Science of the Total Environment (2021) 796, (S0048969721040079), (10.1016/j.scitotenv.2021.148935))

The authors regret that the printed version of the above article contained an omission of an individual deserving of co-authorship. The correct and final version follows. The authors would like to apologise for any inconvenience caused. \u3c Reyd A. Smith1⁎, David J. Yurkowski2, Kyle J.L. Parkinson1, Jérôme Fort3, Holly L. Hennin4, H. Grant Gilchrist4, Keith A. Hobson5, Mark L. Mallory6, Paco Bustamante3, Jóhannis Danielsen7, Svend E. Garbus8, Sveinn A. Hanssen9, Jón Einar Jónsson10, Christopher J. Latty11, Ellen Magnúsdóttir10, Børge Moe9, Glen J. Parsons12, Christian Sonne8, Grigori Tertitski13, and Oliver P. Love1\u3e Windsor, Windsor, Ontario, Canada, N9B 3P4 2 Fisheries and Oceans Canada, Winnipeg, Manitoba, Canada, R3T 2N6 3 Littoral, Environnement et Sociétés (LIENSs), UMR 7266 CNRS – La Rochelle University, La Rochelle, France, FR-17000 4 Environment and Climate Change Canada, Ottawa, Ontario, Canada, K0A 1H0. 5 Western University, London, Ontario, Canada, N6A 3K7 6Acadia University, Wolfville, Nova Scotia, Canada, B4P 2R6 7 Faroe Marine Research Institute, Tórshavn, Faroe Islands, FO-110 8 Aarhus University, Roskilde, Denmark, DK-4000 9 Norwegian Institute for Nature Research, Tromsø, Norway, N-9296 10 University of Iceland\u27s Research Centre at Snæfellsnes, Hafnargata 3, 340, Stykkishólmur, Iceland 11 Arctic National Wildlife Refuge, U.S. Fish and Wildlife Service, Fairbanks, Alaska, United States, 99701 12 Nova Scotia Department of Lands and Forestry, Kentville, Nova Scotia, Canada, B4N 4E5 13 Institute of Geography of the Russian Academy of Sciences, Moscow, Russia, 119017\u3

Using citizen science image analysis to measure seabird phenology

Developing standardized methodology to allow efficient and cost-effective ecological data collection, particularly at scale, is of critical importance for understanding species' declines. Remote camera networks can enable monitoring across large spatiotemporal scales and at relatively low researcher cost, but manually analysing images and extracting biologically meaningful data is time-consuming. Citizen science image analysis could reduce researcher workload and increase output from large datasets, while actively raising awareness of ecological and conservation issues. Nevertheless, testing the validity of citizen science data collection and the retention of volunteers is essential before integrating these approaches into long-term monitoring programmes. In this study, we used data from a Zooniverse citizen science project, Seabird Watch, to investigate changes in breeding timing of a globally declining seabird species, the Black-legged Kittiwake Rissa tridactyla. Time-lapse cameras collected >200 000 images between 2014 and 2023 across 11 locations covering the species' North Atlantic range (51.7°N–78.9°N), with over 35 000 citizen science volunteers ‘tagging’ adult and juvenile Kittiwakes in images. Most volunteers (81%) classified images for only a single day, and each volunteer classified a median of five images, suggesting that high volunteer recruitment rates are important for the project's continued success. We developed a standardized method to extract colony arrival and departure dates from citizen science annotations, which did not significantly differ from manual analysis by a researcher. We found that Kittiwake colony arrival was 2.6 days later and departure was 1.2 days later per 1° increase in latitude, which was consistent with expectations. Year-round monitoring also showed that Kittiwakes visited one of the lowest latitude colonies, Skellig Michael (51.8°N), during winter, whereas birds from a colony at similar latitude, Skomer Island (51.7°N), did not. Our integrated time-lapse camera and citizen science system offers a cost-effective means of measuring changes in colony attendance and subsequent breeding timing in response to environmental change in cliff-nesting seabirds. This study is of wide relevance to a broad range of species that could be monitored using time-lapse photography, increasing the geographical reach and international scope of ecological monitoring against a background of rapidly changing ecosystems and challenging funding landscapes

Facile route to conformal hydrotalcite coatings over complex architectures:a hierarchically ordered nanoporous base catalyst for FAME production

An alkali- and nitrate-free hydrotalcite coating has been grafted onto the surface of a hierarchically ordered macroporous-mesoporous SBA-15 template via stepwise growth of conformal alumina adlayers and their subsequent reaction with magnesium methoxide. The resulting low dimensional hydrotalcite crystallites exhibit excellent per site activity for the base catalysed transesterification of glyceryl triolein with methanol for FAME production

The chromatin-remodeling factor CHD4 coordinates signaling and repair after DNA damage

The CHD4 helicase is identified as a new component of the genome surveillance machinery in a proteomic screen for factors enriched on chromatin after ionizing radiation (see also related paper by Smeenk et al. in this issue)

APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment

Faithful chromosome segregation during mitosis depends on the Spindle Assembly Checkpoint (SAC) that monitors kinetochore attachment to the mitotic spindle. Unattached kinetochores generate mitotic checkpoint proteins complexes (MCCs) that bind and inhibit the Anaphase Promoting Complex/Cyclosome (APC/C). How the SAC proficiently inhibits the APC/C but still allows its rapid activation when the last kinetochore attaches to the spindle is important to understand how cells maintain genomic stability. We show that the APC/C subunit APC15 is required for the turnover of the APC/C co-activator Cdc20 and release of MCCs during SAC signalling but not for APC/C activity per se. In the absence of APC15, MCCs and ubiquitylated Cdc20 remain ‘locked’ onto the APC/C, which prevents the ubiquitylation and degradation of Cyclin B1 when the SAC is satisfied. We conclude that APC15 mediates the constant turnover of Cdc20 and MCCs on the APC/C to allow the SAC to respond to the attachment state of kinetochores