2003 Habitat Maps derived from Grey Nurse Shark (GNS) Project of Wolf Rock, Double Island Point, Queensland, Australia

Surveying habitats critical to the survival of grey nurse sharks in South-East Queensland has mapped critical habitats, gathered species inventories and developed protocols for ecological monitoring of critical habitats in southern Queensland. This information has assisted stakeholders with habitat definition and effective management. In 2002 members of UniDive applied successfully for World Wide Fund for Nature, Threatened Species Network funds to map the critical Grey Nurse Shark Habitats in south east Queensland. UniDive members used the funding to survey, from the boats of local dive operators, Wolf Rock at Double Island Point, Gotham, Cherub's Cave, Henderson's Rock and China Wall at North Moreton and Flat Rock at Point Look Out during 2002 and 2003. These sites are situated along the south east Queensland coast and are known to be key Grey Nurse Shark aggregation sites. During the project UniDive members were trained in mapping and survey techniques that include identification of fish, invertebrates and substrate types. Training was conducted by experts from the University of Queensland (Centre of Marine Studies, Biophysical Remote Sensing) and the Queensland Parks and Wildlife Service who are also UniDive members. The monitoring methods (see methods) are based upon results of the UniDive Coastcare project from 2002, the international established Reef Check program and research conducted by Biophysical Remote Sensing and the Centre of Marine Studies. Habitats were mapped using a combination of towed GPS photo transects, aerial photography, bathymetry surveys and expert knowledge. This data provides georeferenced information regarding the major features of each of Sites mapped including Wolf Rock

Spatial overlap of grey seals and fisheries in Irish waters, some new insights using telemetry technology and VMS

Seals and humans often target the same food resource, leading to competition. This is of mounting concern with fish stocks in global decline. Grey seals were tracked from southeast Ireland, an area of mixed demersal and pelagic fisheries, and overlap with fisheries on the Celtic Shelf and Irish Sea was assessed. Overall, there was low overlap between the tagged seals and fisheries. However, when we separate active (e.g. trawls) and passive gear (e.g. nets, lines) fisheries, a different picture emerged. Overlap with active fisheries was no different from that expected under a random distribution, but overlap with passive fisheries was significantly higher. This suggests that grey seals may be targeting the same areas as passive fisheries and/or specifically targeting passive gear. There was variation in foraging areas between individual seals suggesting habitat partitioning to reduce intra-specific competition or potential individual specialisation in foraging behaviour. Our findings support other recent assertions that seal/fisheries interactions in Irish waters are an issue in inshore passive fisheries, most likely at the operational and individual level. This suggests that seal population management measures would be unjustifiable, and mitigation is best focused on minimizing interactions at nets.

Age, body mass, mass change and dispersal distance of suckling and weaned grey seal (Halichoerus grypus) pups

Grey seal, Halichoerus grypus, pups in the breeding colony at Froan, Norway, have a bimodal pattern of early aquatic behaviour. About 40% of the pups spend their time ashore to save energy, which can be allocated to growth or deposition of energy-rich adipose tissue. The other 60% of the pups enter the sea during suckling and the early postweaning period, and disperse to other locations within the breeding colony. Pups may swim distances up to 12 km. Neonatal aquatic dispersal behaviour may lead to increased energy expenditure for thermoregulation and swimming, and thus lead to a low rate of body mass gain during suckling and a high rate of body mass loss after weaning. Thus, we examined relationships between natal aquatic dispersal behaviour and change in body mass (DeltaBM) in suckling and weaned pups. Suckling pups that had dispersed >2000 m had a significantly lower DBM than suckling pups that dispersed <2000 m or that did not disperse. In weaned pups, there were no effects of aquatic dispersal behaviour on DBM. We suggest that the bimodal natal aquatic dispersal behaviour in grey seals at the study site reflects two different strategies for postweaning survival: to stay ashore and get fat, or to take a swim and acquire diving and feeding skills.

Researching suicide, attempted suicide and near-lethal self-harm by offenders in community settings: Challenges for future research

Suicide is a serious international health problem and is more likely to occur in vulnerable populations such as offenders. There is an abundance of research into suicides of prisoners, but few studies have been carried out on suicides of offenders serving community sentences. This article identifies and evaluates the limited research that is available. Recommendations for future research are made, including how in-depth interviews can provide important information about near lethal incidents from the service users’ perspective, and how international comparisons could be helpful in understanding this problem further.

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G₁ -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML.

Adiponectin and insulin in grey seals during suckling and fasting: relationship with nutritional state and body mass during nursing in mothers and pups

Animals that fast during breeding and/or development, such as phocids, must regulate energy balance carefully to maximize reproductive fitness and survival probability. Adiponectin, produced by adipose tissue, contributes to metabolic regulation by modulating sensitivity to insulin, increasing fatty acid oxidation by liver and muscle, and promoting adipogenesis and lipid storage in fat tissue. We tested the hypotheses that (1) circulating adiponectin, insulin, or relative adiponectin gene expression is related to nutritional state, body mass, and mass gain in wild gray seal pups; (2) plasma adiponectin or insulin is related to maternal lactation duration, body mass, percentage milk fat, or free fatty acid (FFA) concentration; and (3) plasma adiponectin and insulin are correlated with circulating FFA in females and pups. In pups, plasma adiponectin decreased during suckling (linear mixed-effects model [LME]: T = 4.49; P < 0.001) and the early postweaning fast (LME: T = 3.39; P = 0.004). In contrast, their blubber adiponectin gene expression was higher during the early postweaning fast than early in suckling (LME: T = 2.11; P = 0.046). Insulin levels were significantly higher in early (LME: T = 3.52; P = 0.004) and late (LME: T = 6.99; P < 0.001) suckling than in fasting and, given the effect of nutritional state, were also positively related to body mass (LME: T = 3.58; P = 0.004). Adiponectin and insulin levels did not change during lactation and were unrelated to milk FFA or percentage milk fat in adult females. Our data suggest that adiponectin, in conjunction with insulin, may facilitate fat storage in seals and is likely to be particularly important in the development of blubber reserves in pups.

Liver glucose-6-phosphatase proteins in suckling and weaned grey seal pups: structural similarities to other mammals and relationship to nutrition, insulin signalling and metabolite levels

Phocid seals have been proposed as models for diabetes because they exhibit limited insulin response to glucose, high blood glucose and increasing insulin resistance when fasting. Liver glucose-6-phosphatase (G6Pase) catalyses the final step in glucose production and is central to glucose regulation in other animals. G6Pase comprises a translocase (SLC37A4) and a catalytic subunit (G6PC). G6PC and SLC37A4 expression and activity are normally regulated by nutritional state and glucostatic hormones, particularly insulin, and are elevated in diabetes. We tested the hypotheses that (1) grey seal G6PC and SLC37A4 cDNA and predicted protein sequences differ from other species’ at functional sites, (2) relative G6Pase protein abundances are lower during feeding than fasting and (3) relative G6Pase protein abundances are related to insulin, insulin receptor phosphorylation and key metabolite levels. We show that G6PC and partial SLC37A4 cDNA sequences encode proteins sharing 82–95 % identity with other mammals. Seal G6PC contained no differences in sites responsible for activity, stability or subcellular location. Several substitutions in seal SLC37A4 were predicted to be tolerated with low probability, which could affect glucose production. Suckling pups had higher relative abundance of both subunits than healthy, postweaned fasting pups. Furthermore, relative G6PC abundance was negatively related to glucose levels. These findings contrast markedly with the response of relative hepatic G6Pase abundance to feeding, fasting, insulin, insulin sensitivity and key metabolites in other animals, and highlight the need to understand the regulation of enzymes involved in glucose control in phocids if these animals are to be informative models of diabetes.

The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony

Seals must manage their energy reserves carefully while they fast on land to ensure that they go to sea with sufficient fuel to sustain them until they find food. Glucocorticoids (GCs) have been implicated in the control of fuel metabolism and termination of fasting in pinnipeds. Here we tested the hypothesis that dexamethasone, an artificial GC, increases fat and protein catabolism, and induces departure from the breeding colony in wild, fasting grey seal pups. A single intramuscular dose of dexamethasone completely suppressed cortisol production for 24–72 h, demonstrating activation of GC receptors. In experiment 1, we compared the effects of a single dose of dexamethasone or saline administered 10 days after weaning on fasting mass and body composition changes, cortisol, blood urea nitrogen (BUN) and glucose levels, and timing of departure from the colony. In experiment 2, we investigated the effects of dexamethasone on short-term (5 days) changes in mass loss, body composition and BUN levels. In experiment 1, dexamethasone induced a short-lived increase in mass loss, but there was no difference in timing of departure between dexamethasone- and saline-treated pups (N=10). In experiment 2, dexamethasone increased protein and water loss and prevented a decrease in BUN levels (N=11). Our data suggest changes in cortisol contribute to regulation of protein catabolism in fasting seal pups, irrespective of the sex of the animal, but do not terminate fasting. By affecting the rate of protein depletion, lasting changes in cortisol levels could influence the amount of time seal pups have to find food, and thus may have important consequences for their survival.

Effects of handling regime and sex on changes in cortisol, thyroid hormones and body mass in fasting grey seal pups

Survival of seal pups may be affected by their ability to respond appropriately to stress. Chronic stress can adversely affect secretion of cortisol and thyroid hormones, which contribute to the control of fuel utilisation. Repeated handling could disrupt the endocrine response to stress and/or negatively impact upon mass changes during fasting. Here we investigated the effects of handling regime on cortisol and thyroid hormone levels, and body mass changes, in fasting male and female grey seal pups (Halichoerus grypus). Females had higher thyroid hormone levels than males throughout fasting and showed a reduction in cortisol midway through the fast that was not seen in males. This may reflect sex-specific fuel allocation or development. Neither handling frequency nor cumulative contact time affected plasma cortisol or thyroid hormone levels, the rate of increase in cortisol over the first five minutes of physical contact or the pattern of mass loss during fasting in either sex. The endocrine response to stress and the control of energy balance in grey seal pups appear to be robust to repeated, short periods of handling. Our results suggest that routine handling should have no additional impact on these animals than general disturbance caused by researchers moving around the colony.

Effects of mass and body composition on fasting fuel utilisation in grey seal pups (Halichoerus grypus Fabricius): an experimental study using supplementary feeding

This study used supplementary feeding to test the hypothesis that fuel partitioning during the postweaning fast in grey seal pups is affected by size and composition of energy reserves at weaning, and by extra provisioning. Mass and body composition changes were measured during suckling and fasting to investigate the effect of natural differences in energy reserves at weaning on subsequent allocation of fat and protein to energy use. We fed seven pups for 5 days after weaning, to investigate the effect of increased fuel availability, and particularly protein, on fuel utilisation. After correcting for protein used during the moult, the proportional contribution of fat was 86–99% of total energy use. Pups with greater energy reserves, i.e. those that were heavier and fatter at weaning, had higher rates of fat and energy use. There was no significant relationship between adiposity at weaning and proportional contribution of fat to energy use, perhaps due to a limited sample size or range of body masses and adiposity. Supplemented individuals used energy, specifically fat, much faster and utilised proportionally less of their endogenous protein by departure than non-supplemented individuals. Fat metabolism contributed a similar percentage to daily energy use in both groups. These findings show that pups spare protein, even when energy use is dramatically increased. Pups that receive greater maternal provisioning and lay down more protein may have increased survival chances at sea. This study highlights the importance of protein reserves in first year survival of grey seal pups.