Using blubber explants to investigate adipose function in grey seals:glycolytic, lipolytic and gene expression responses to glucose and hydrocortisone

Adipose tissue is fundamental to energy balance, which underpins fitness and survival. Knowledge of adipose regulation in animals that undergo rapid fat deposition and mobilisation aids understanding of their energetic responses to rapid environmental change. Tissue explants can be used to investigate adipose regulation in wildlife species with large fat reserves, when opportunities for organismal experimental work are limited. We investigated glucose removal, lactate, glycerol and NEFA accumulation in media, and metabolic gene expression in blubber explants from wild grey seals. Glycolysis was higher in explants incubated in 25 mM glucose (HG) for 24 h compared to controls (C: 5.5 mM glucose). Adipose-derived lactate likely contributes to high endogenous glucose production in seals. Lipolysis was not stimulated by HG or high hydrocortisone (HC: 500 nM hydrocortisone) and was lower in heavier animals. HC caused NEFA accumulation in media to decrease by ~30% relative to C in females, indicative of increased lipogenesis. Lipolysis was higher in males than females in C and HG conditions. Lower relative abundance of 11-β-hydroxysteroid dehydrogenase 1 mRNA in HG explants suggests glucose involvement in blubber cortisol sensitivity. Our findings can help predict energy balance responses to stress and nutritional state in seals, and highlight the use of explants to study fat tissue function in wildlife

Persistent organic pollutant burden, experimental POP exposure and tissue properties affect metabolic profiles of blubber from grey seal pups

Persistent organic pollutants (POPs) are toxic, ubiquitous, resist breakdown, bioaccumulate in living tissue and biomagnify in food webs. POPs can also alter energy balance in humans and wildlife. Marine mammals experience high POP concentrations, but consequences for their tissue metabolic characteristics are unknown. We used blubber explants from wild, grey seal (Halichoerus grypus) pups to examine impacts of intrinsic tissue POP burden and acute experimental POP exposure on adipose metabolic characteristics. Glucose use, lactate production and lipolytic rate differed between matched inner and outer blubber explants from the same individuals and between feeding and natural fasting. Glucose use decreased with blubber dioxin-like PCBs (DL-PCB) and increased with acute experimental POP exposure. Lactate production increased with DL-PCBs during feeding, but decreased with DL-PCBs during fasting. Lipolytic rate increased with blubber dichlorodiphenyltrichloroethane (DDT) and its metabolites (DDX) in fasting animals, but declined with DDX when animals were feeding. Our data show that POP burdens are high enough in seal pups to alter adipose function early in life, when fat deposition and mobilisation are vital. Such POP-induced alterations to adipose glucose use may significantly alter energy balance regulation in marine top predators with the potential for long term impacts on fitness and survival

FOXA1 mutations in hormone-dependent cancers.

The forkhead protein, FOXA1, is a critical interacting partner of the nuclear hormone receptors, oestrogen receptor-α (ER) and androgen receptor (AR), which are major drivers of the two most common cancers, namely breast and prostate cancer. Over the past few years, progress has been made in our understanding of how FOXA1 influences nuclear receptor function, with both common and distinct roles in the regulation of ER or AR. Recently, another level of regulation has been described, with the discovery that FOXA1 is mutated in 1.8% of breast and 3-5% prostate cancers. In addition, a subset of both cancer types exhibit amplification of the genomic region encompassing the FOXA1 gene. Furthermore, there is evidence of somatic changes that influence the DNA sequence under FOXA1 binding regions, which may indirectly influence FOXA1-mediated regulation of ER and AR activity. These recent observations provide insight into the heterogeneity observed in ER and AR driven cancers

Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

BACKGROUND Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. FINDINGS A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. CONCLUSION The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.This work was funded by the Royal Society of Tropical Medicine and Hygiene through a Dennis Burkitt Fellowship to JJM. ARD is supported by the Economic and Social Research Council. JJM is supported by a Wellcome Trust Research Training Fellowship (GR074833MA)

Trend Identification in Twentieth-Century U.S. Snowfall: The Challenges

There is an increasing interest in examining long-term trends in measures of snow climatology. An examination of the U.S. daily snowfall records for 1900–2004 revealed numerous apparent inconsistencies. For example, long-term snowfall trends among neighboring lake-effect stations differ greatly from insignificant to +100% century -1. Internal inconsistencies in the snow records, such as a lack of upward trends in maximum seasonal snow depth at stations with large upward trends in snowfall, point to inhomogeneities. Nationwide, the frequency of daily observations with a 10:1 snowfall-to-liquid-equivalent ratio declined from 30% in the 1930s to a current value of around 10%, a change that is clearly due to observational practice. There then must be biases in cold-season liquid-equivalent precipitation, or snowfall, or both. An empirical adjustment of snow-event, liquid-equivalent precipitation indicates that the potential biases can be statistically significant. Examples from this study show that there are nonclimatic issues that complicate the identification of and significantly change the trends in snow variables. Thus, great care should be taken in interpretation of time series of snow-related variables from the Cooperative Observer Program (COOP) network. Furthermore, full documentation of optional practices should be required of network observers so that future users of these data can properly account for such practices

Duration of untreated eating disorder and relationship to outcomes: A systematic review of the literature

Objective: This systematic review assesses the average duration of untreated eating disorder (DUED) in help‐seeking populations at the time of first eating disorder (ED) treatment and investigates the relationship between DUED and symptom severity/clinical outcomes. / Method: PRISMA guidelines were followed throughout. Selected studies provided information on either: (i) length of DUED, (ii) components of DUED, (iii) cross‐sectional associations between DUED and symptom severity, (iv) associations between DUED and clinical outcomes, or (v) experimental manipulation of DUED. Study quality was assessed. / Results: Fourteen studies from seven countries were included. Across studies, average DUED weighted by sample size was 29.9 months for anorexia nervosa, 53.0 months for bulimia nervosa and 67.4 months for binge eating disorder. A younger age at time of first treatment was indicative of shorter DUED. Retrospective studies suggest that a shorter DUED may be related to a greater likelihood of remission. Manipulation of DUED by shortening service‐related delays may improve clinical outcomes. / Conclusions: Data on length of DUED provide a benchmark for early intervention in EDs. Preliminary evidence suggests DUED may be a modifiable factor influencing outcomes in EDs. To accurately determine the role of DUED, definition and measurement must be uniformly operationalised

Trends in Twentieth-Century U.S. Extreme Snowfall Seasons

Temporal variability in the occurrence of the most extreme snowfall years, both those with abundant snowfall amounts and those lacking snowfall, was examined using a set of 440 quality-controlled, homogenous U.S. snowfall records. The frequencies with which winter-centered annual snowfall totals exceeded the 90th and 10th percentile thresholds at individual stations were calculated from 1900–01 to 2006–07 for the conterminous United States, and for 9 standard climate regions. The area-weighted conterminous U.S. results do not show a statistically significant trend in the occurrence of either high or low snowfall years for the 107-yr period, but there are regional trends. Large decreases in the frequency of low-extreme snowfall years in the west north-central and east north-central United States are balanced by large increases in the frequency of low-extreme snowfall years in the Northeast, Southeast, and Northwest. During the latter portion of the period, from 1950–51 to 2006–07, trends are much more consistent, with the United States as a whole and the central and northwest U.S. regions in particular showing significant declines in high-extreme snowfall years, and four regions showing significant increases in the frequency of low-extreme snowfall years (i.e., Northeast, Southeast, south, and Northwest). In almost all regions of the United States, temperature during November–March is more highly correlated than precipitation to the occurrence of extreme snowfall years. El Nin ̃ o events are strongly associated with an increase in low-extreme snowfall years over the United States as a whole, and in the northwest, northeast, and central regions. A reduction in low-extreme snowfall years in the Southwest is also associated with El Nin ̃ o. The impacts of La Nin ̃ a events are strongest in the south and Southeast, favoring fewer high-extreme snowfall years, and, in the case of the south, more low-extreme snowfall years occur. The Northwest also has a significant reduction in the chance of a low-extreme snowfall year during La Nin ̃ a. A combination of trends in temperature in the United States and changes in the frequency of ENSO modes influences the frequency of extreme snowfall years in the United States