Reproductive Failure in UK Harbour Porpoises Phocoena phocoena : Legacy of Pollutant Exposure?

This research was supported by a Marie Curie International Outgoing Fellowship within the Seventh European Community Framework Programme (Project Cetacean-stressors, PIOF-GA-2010-276145 to PDJ and SM). Additional funding was provided through the Agreement on the Conservation of Small Cetaceans of the Baltic, North East Atlantic, Irish and North Seas (ASCOBANS) (Grants SSFA/2008 and SSFA / ASCOBANS / 2010 / 5 to SM). Analysis of Scottish reproductive and teeth samples was funded by the EC-funded BIOCET project (BIOaccumulation of persistent organic pollutants in small CETaceans in European waters: transport pathways and impact on reproduction, grant EVK3-2000-00027 to GJP), and Marine Scotland (GJP). Samples examined in this research were collected under the collaborative Cetacean Strandings Investigation Programme (http://ukstrandings.org/), which is funded by the Department for Environment, Food and Rural Affairs (Defra) and the UK’s Devolved Administrations in Scotland and Wales (http://sciencesearch.defra.gov.uk/Defaul​t.aspx?Menu=Menu&Module=More&Location=No​ne&Completed=0&ProjectID=15331) (grants to PDJ, RD). UK Defra also funded the chemical analysis under a service-level agreement with the Centre for Environment, Fisheries and Aquaculture Science (grants to RJL, JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

T cells that cannot respond to TGF-β escape control by CD4+CD25+ regulatory T cells

CD4+CD25+ regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-β (TGF-β) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4+CD45RBhigh T cells that express a dominant negative TGF-β receptor type II (dnTβRII) and therefore cannot respond to TGF-β, escape control by T reg cells in vivo. CD4+CD25+ T reg cells from the thymus of dnTβRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-β is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTβRII CD4+CD25+ population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4+CD25+ T reg cells develop normally in the absence of TGF-β1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-β1−/− T reg cells was abrogated by anti–TGF-β monoclonal antibody, indicating that functional TGF-β can be provided by a non–T reg cell source

A pilot randomized controlled trial of time-intensive Cognitive Behaviour Therapy for postpartum OCD:effects on maternal symptoms, mother-infant interactions and attachment

BackgroundThere is increasing recognition that perinatal anxiety disorders are both common and potentially serious for mother and child. Obsessive–compulsive disorder (OCD) can be triggered or exacerbated in the postpartum period, with mothers reporting significant effects on parenting tasks. However, there is little evidence concerning their effective treatment or the impact of successful treatment on parenting.MethodA total of 34 mothers with OCD and a baby of 6 months old were randomized into either time-intensive cognitive–behaviour therapy (iCBT) or treatment as usual (TAU). iCBT took place after randomization at 6 months postpartum and was completed by 9 months. Maternal symptomatology, sensitivity in mother–infant interactions and parenting were assessed at baseline and reassessed at 12 months postpartum. At 12 months attachment was also assessed using Ainsworth's Strange Situation Procedure. A healthy control group of mothers and infants (n = 37) underwent the same assessments as a benchmark.ResultsiCBT was successful in ameliorating maternal symptoms of OCD (controlled effect size = 1.31–1.90). However, mother–infant interactions were unchanged by treatment and remained less sensitive in both OCD groups than a healthy control group. The distribution of attachment categories was similar across both clinical groups and healthy controls with approximately 72% classified as secure in each group.ConclusionsiCBT is an effective intervention for postpartum OCD. Sensitive parenting interactions are affected by the presence of postpartum OCD and this is not improved by successful treatment of OCD symptoms. However, the overall attachment bond appears to be unaffected. Longitudinal studies are needed to explore the impact of postpartum OCD as the child develops.</jats:sec

The novel anti-cancer fluoropyrimidine NUC-3373 is a potent inhibitor of thymidylate synthase and an effective DNA-damaging agent

Funding: GMZ and CMC are funded by research grant from NuCana plc. PT is funded by IBioIC, CMC is funded by the Wellcome trust (217078/Z/19/Z).Introduction Fluoropyrimidines, principally 5-fluorouracil (5-FU), remain a key component of chemotherapy regimens for multiple cancer types, in particular colorectal and other gastrointestinal malignancies. To overcome key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, NUC-3373, a phosphoramidate transformation of 5-fluorodeoxyuridine, was designed to improve the efficacy and safety profile as well as the administration challenges associated with 5-FU. Methods Human colorectal cancer cell lines HCT116 and SW480 were treated with sub-IC50 doses of NUC-3373 or 5-FU. Intracellular activation was measured by LC–MS. Western blot was performed to determine binding of the active anti-cancer metabolite FdUMP to thymidylate synthase (TS) and DNA damage. Results We demonstrated that NUC-3373 generates more FdUMP than 5-FU, resulting in a more potent inhibition of TS, DNA misincorporation and subsequent cell cycle arrest and DNA damage in vitro. Unlike 5-FU, the thymineless death induced by NUC-3373 was rescued by the concurrent addition of exogenous thymidine. 5-FU cytotoxicity, however, was only reversed by supplementation with uridine, a treatment used to reduce 5-FU-induced toxicities in the clinic. This is in line with our findings that 5-FU generates FUTP which is incorporated into RNA, a mechanism known to underlie the myelosuppression and gastrointestinal inflammation associated with 5-FU. Conclusion Taken together, these results highlight key differences between NUC-3373 and 5-FU that are driven by the anti-cancer metabolites generated. NUC-3373 is a potent inhibitor of TS that also causes DNA-directed damage. These data support the preliminary clinical evidence that suggest NUC-3373 has a favorable safety profile in patients.Publisher PDFPeer reviewe

In vivo formation of natural HgSe nanoparticles in the liver and brain of pilot whales

Acknowledgments Z.G. thanks to the College of Physical Sciences at University of Aberdeen and Chevron USA for the provided studentship. P.M.K. is the recipient of an Australian Research Council Future Fellowship (FT120100277). Parts of this research were undertaken on the XFM beamline at the Australian Synchrotron, Victoria, Australia. The assistance of Daryl Howard (XFM beamline, Australian Synchrotron) is acknowledged. Although EPA contributed to this article, the research presented was not performed by or funded by EPA and was not subject to EPA's quality system requirements. Consequently, the views, interpretations, and conclusions expressed in this article are solely those of the authors and do not necessarily reflect or represent EPA's views or policies. MRCAT operations are supported by the Department of Energy and the MRCAT member institutions. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. The authors declare no competing financial interests. F.L.R. and A.B. acknowledge Scottish Marine Animal Stranding Scheme and Marine Scotland for funding. Author Contributions E.M.K and J.F. designed the experiments. Z.G. measured total Hg and conducted Hg speciation. Total Se was determined by A.R. and Z.G. M.M.L. performed Se speciation and 2D imaging by LA-ICP-MS was done by D.S.U. XANES was performed by K.S. and XRF by E.L. and P.M.K. Samples were obtained by E.M.K. through A.B. and age determination was done by F.R. spICP-MS was performed by E.H.L., K.L., G.W. and Z.G. The manuscript was written by Z.G. and all authors discussed the results and commented on the manuscript.Peer reviewedPublisher PD

Inter-species differences in polychlorinated biphenyls patterns from five sympatric species of odontocetes : Can PCBs be used as tracers of feeding ecology?

The authors gratefully acknowledge the assistance of volunteers from the Galician (CEMMA) and Portuguese (SPVS) stranding networks. The authors would like to thank R. Gallois and C. Trichet for their participation on total lipid content analysis. P. Méndez-Fernandez was supported during the research period through a PhD grant from the Fundação do Ministério de Ciência e Tecnologia de Portugal and ANIMATE project (SFRH/BD/36766/2007) and through a Science Without Borders (CSF) young talent postdoctoral grant of the Brazilian government. G. J. Pierce acknowledges support from the EU ANIMATE project (MEXC-CT-2006-042337), University of Aveiro and Caixa Geral de Depósitos (Portugal).Peer reviewedPostprin

Patterns and trends in cetacean strandings on the Galician coast and their relationship with oceanography and fishing effort

Poster.-- ICES 2014 Annual Science Conference, 15- 19 September 2014, A CoruñaStrandings provide valuable information on the presence and relative abundance of cetaceans in an area. The spatial, inter-annual and seasonal variation in the number of strandings may reflect the variability in cetacean abundance. However, this signal can be masked by other factors which are responsible both for the mortality of the dolphins and the probability that they reach the shore once they are dead. We analysed the time series of cetacean strandings in Galicia (NW Spain), available since 1990, with the aim of determining the trends and variability of strandings. We found that seasonal and inter-annual variation in the number of strandings is highly correlated with the oceanographic conditions most prevalent in each period. Moreover, a more detailed analysis of these effects should be carried out, and the use of further applicable indices (fishing effort rather than landings) may improve the explained part of the models, thus allowing us to disentangle oceanographic effects and to obtain relative seasonal and annual abundancesN

Impacts of organic pollutants on cetaceans in NW Spain

Poster.-- Pollution 2025: Intersessional Workshop, 21 October 2021N