Some endocrinological studies into periparturient reproduction in the cow

This thesis describes a study of some hormonal, behavioural and gonadal changes during the peri- and post-parturient period of a group of suckled cows. The investigation was commenced just prior to calving, continued through the post-partum anoestrus period, and terminated when pregnancy was established. To enable ovarian functional changes to be monitored radioimmunoassays were developed for progesterone, oestrogens and androgens. Validation of these assays for measurement of the steroids in peripheral plasma samples was by recognised reliability criteria. In addition, by applying the methods to samples from cows during the oestrous cycle comparison of the results with ovarian structural changes, and with the levels reported by other workers was possible. At calving observations on the inter-relationship of progesterone, oestrogens, androgens and cortisol revealed alterations in the peripheral plasma levels of these hormones which gave information on possible sources of secretion, and suggested functional roles for these steroids in the process of birth. Post-partum the peripheral plasma levels of progesterone, oestrogens, and androgens were related to the presence of follicles and corpora lutea in the ovaries, to the size and degree of turgidity of the uterine horns, and to behavioural changes typifying prooestrus and oestrus. Subdivision of the anoestrus period on the basis of endocrinological and gonadal structure changes, and comparison of silent, overt and false heats during the period of study elucidated some aspects of the aetiology of this period of altered reproductive function. In animals in which pregnancy was established luteal function was compared to that observed earlier in the post-partura period and to dioestrus progesterone levels in cycling cows. The clinical significance of cystic ovarian structures recorded mainly during early pregnancy was studied. The results of the thesis raised the question of the value of some of the accepted parameters to determine if oestrous cycles were occurring in cows. In addition the accuracy of endocrinological, behavioural and structural changes in the reproductive tract as a means of assessing the stage of the oestrous cycle were discussed

Understanding radionuclide migration from the D1225 Shaft, Dounreay, Caithness, UK

A 65 m vertical shaft was sunk at Dounreay in the 1950s to build a tunnel for the offshore discharge of radioactive effluent from the various nuclear facilities then under construction. In 1959, the Shaft was licensed as a disposal facility for radioactive wastes and was routinely used for the disposal of ILW until 1970. Despite the operation of a hydraulic containment scheme, some radioactivity is known to have leaked into the surrounding rocks. Detailed logging, together with mineralogical and radiochemical analysis of drillcore has revealed four distinct bedding-parallel zones of contamination. The data show that Sr-90 dominates the bulk beta/gamma contamination signal, whereas Cs-137 and Pu-248/249 are found only to be weakly mobile, leading to very low activities and distinct clustering around the Shaft. The data also suggest that all uranium seen in the geosphere is natural in origin. At the smaller scale, contamination adjacent to fracture surfaces is present within a zone of enhanced porosity created by the dissolution of carbonate cements from the Caithness flagstones during long-term rockwater interactions. Quantitative modelling of radionuclide migration, using the multiphysics computer code QPAC shows the importance of different sorption mechanisms and different mineralogical substrates in the Caithnesss flagstones in controlling radionuclide migration

Incentive-based approaches to sustainable fisheries

The failures of traditional target-species management have led many to propose an ecosystem approach to fisheries to promote sustainability. The ecosystem approach is necessary, especially to account for fishery-ecosystem interactions, but by itself is not sufficient to address two important factors contributing to unsustainable fisheries — inappropriate incentives bearing on fishers, and the ineffective governance that frequently exists in commercial, developed fisheries managed primarily by total harvest limits and input-controls. We contend that much greater emphasis must be placed on fisher motivation when managing fisheries. Using evidence from more than a dozen ‘natural experiments’ in commercial fisheries, we argue that incentive-based approaches that better specify community, individual harvest, or territorial rights and also price ecosystem services — coupled with public research, monitoring and effective oversight — promote sustainable fisheries.incentives, sustainability, rights, fisheries management

Incentive-based approaches to sustainable fisheries (now replaced by EEN0508)

Using examples from more than a dozen fisheries, we highlight the failures of ‘command control’ management and show that approaches that empower fishers with the incentives and the mandate to be co-custodians of the marine environment can promote sustainability. Evidence is provided that where harvesters share well-defined management responsibilities over fish, and experience both the pain of overexploitation and the gains from conservation, they are much more likely to protect fish stocks and habitat. The key insight is that to maintain marine ecosystems for present and future generations, fishing incentives must be compatible with long-term goals of sustainability.incentives, sustainability, rights, fisheries management

Structural characterization of CYP144A1 - a cytochrome P450 enzyme expressed from alternative transcripts in Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) causes the disease tuberculosis (TB). The virulent Mtb H37Rv strain encodes 20 cytochrome P450 (CYP) enzymes, many of which are implicated in Mtb survival and pathogenicity in the human host. Bioinformatics analysis revealed that CYP144A1 is retained exclusively within the Mycobacterium genus, particularly in species causing human and animal disease. Transcriptomic annotation revealed two possible CYP144A1 start codons, leading to expression of (i) a "full-length" 434 amino acid version (CYP144A1-FLV) and (ii) a "truncated" 404 amino acid version (CYP144A1-TRV). Computational analysis predicted that the extended N-terminal region of CYP144A1-FLV is largely unstructured. CYP144A1 FLV and TRV forms were purified in heme-bound states. Mass spectrometry confirmed production of intact, His6-tagged forms of CYP144A1-FLV and -TRV, with EPR demonstrating cysteine thiolate coordination of heme iron in both cases. Hydrodynamic analysis indicated that both CYP144A1 forms are monomeric. CYP144A1-TRV was crystallized and the first structure of a CYP144 family P450 protein determined. CYP144A1-TRV has an open structure primed for substrate binding, with a large active site cavity. Our data provide the first evidence that Mtb produces two different forms of CYP144A1 from alternative transcripts, with CYP144A1-TRV generated from a leaderless transcript lacking a 5'-untranslated region and Shine-Dalgarno ribosome binding site

Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.

The essential enzyme CYP121 is a target for drug development against antibiotic resistant strains of Mycobacterium tuberculosis. A triazol-1-yl phenol fragment 1 was identified to bind to CYP121 using a cascade of biophysical assays. Synthetic merging and optimization of 1 produced a 100-fold improvement in binding affinity, yielding lead compound 2 (KD = 15 μM). Deconstruction of 2 into its component retrofragments allowed the group efficiency of structural motifs to be assessed, the identification of more LE scaffolds for optimization and highlighted binding affinity hotspots. Structure-guided addition of a metal-binding pharmacophore onto LE retrofragment scaffolds produced low nanomolar (KD = 15 nM) CYP121 ligands. Elaboration of these compounds to target binding hotspots in the distal active site afforded compounds with excellent selectivity against human drug-metabolizing P450s. Analysis of the factors governing ligand potency and selectivity using X-ray crystallography, UV-vis spectroscopy, and native mass spectrometry provides insight for subsequent drug development.MEK was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunction with the Cambridge Commonwealth Trust and Cambridge Overseas Trust. AGC and KJM were supported by grants from the BBSRC (Grant No: BB/I019669/1 and BB/I019227/1). GGJ received funding from the Ogden Trust and the Isaac Newton Trust administered through the University of Cambridge Bursary Scheme. DSCH was supported by a Croucher Cambridge International Scholarship awarded in conjunction between the Croucher Foundation and the Cambridge Overseas Trust. SAH was supported by an Oliphant Cambridge Australia Scholarship (App No: 10132070) awarded by the Cambridge Commonwealth Trust. The contributions of LBM and LPSC were supported by funds from the Francis Crick Institute, which receives its core funding principally from Wellcome Trust, Cancer Research UK, and the UK Medical Research Council (to LPSC - MC_UP_A253_1111) and funds from FAPESP, CNPq and CAPES-PDSE (to LBM - 2011/21232-1, 140079/2013-0, 99999.003125/2014-09).This is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/acs.jmedchem.6b0000

A Review of Pink Salmon in the Pacific, Arctic, and Atlantic Oceans

The Northern Hemisphere Pink Salmon Expert Group Meeting was held on October 2–3, 2022 in Vancouver, Canada, immediately preceding the International Year of the Salmon (IYS) Synthesis Symposium. The rapid expansion of pink salmon was the theme for the meeting, and experts came together to discuss the current state of knowledge for pink salmon. Specific topics of focus included the range expansion into the Atlantic and Arctic oceans, trends in distribution and abundance, research and monitoring approaches, potential inter-specific interactions, mitigation efforts, and plans for future collaborations. The outcomes of the meeting were presented at the IYS Synthesis Symposium and are further disseminated through this NPAFC Technical Report. The Executive Summary section of this report provides a brief background, a condensed overview of each topic, and concludes with overarching takeaway messages that are intended to guide future collaborations.publishedVersio

A Review of Pink Salmon in the Pacific, Arctic, and Atlantic Oceans

The Northern Hemisphere Pink Salmon Expert Group Meeting was held on October 2–3, 2022 in Vancouver, Canada, immediately preceding the International Year of the Salmon (IYS) Synthesis Symposium. The rapid expansion of pink salmon was the theme for the meeting, and experts came together to discuss the current state of knowledge for pink salmon. Specific topics of focus included the range expansion into the Atlantic and Arctic oceans, trends in distribution and abundance, research and monitoring approaches, potential inter-specific interactions, mitigation efforts, and plans for future collaborations. The outcomes of the meeting were presented at the IYS Synthesis Symposium and are further disseminated through this NPAFC Technical Report. The Executive Summary section of this report provides a brief background, a condensed overview of each topic, and concludes with overarching takeaway messages that are intended to guide future collaborations.publishedVersio