Molecular basis of copper transport: cellular and physiological functions of Menkes and Wilson disease proteins (ATP7A and ATPB)

Eukaryotic cells prevent copper-induced, free radical damage to cell components by employing copper-binding proteins and transporters that minimize the likelihood of free copper ions existing in the cell. In the cell, copper is actively transported from the cytoplasm during the biosynthesis of secreted coppercontaining proteins and, as a protective measure, when there is an excess of copper. In humans, this is accomplished by two related copper-transporting ATPases (ATP7A and ATP7B), which are the affected genes in two distinct human genetic disorders of copper transport, Menkes disease (copper deficiency) and Wilson disease (copper toxicosis). The study of these ATPases has revealed their molecular mechanisms of copper transport and their roles in physiological copper homeostasis. Both ATP7A and ATP7B are expressed in specific brain regions and neurological abnormalities are important clinical features in Menkes and Wilson disease.

Development of physiological discriminators for the Australasian triage scale

The Consistency of Triage in Victoria’s Emergency Departments Project (2001), funded by the Victorian Department of Human Services, aimed to improve the consistency of application of the Australasian (National) Triage Scale (ATS). One of the major objectives of the project was the development of an education strategy to promote a consistent approach to triage education, leading to the development of the Adult Physiological Discriminators (APDs) for the ATS and Paediatric Physiological Discriminators (PPDs) for the ATS. The guidelines and physiological discriminators were developed in consultation with the Emergency Nurses’ Association of Victoria (ENA Vic.) and clinical nurse educators, lecturers, nurse unit managers and clinicians from a wide variety of Emergency Departments (EDs) across Victoria. Numerous studies have identified varying degrees of inconsistency in the application of the ATS. A number of factors associated with inconsistency in the application of the ATS have also been alluded to in the literature. These range from the wide variation in the experiential and educational requirements of Victorian triage nurses to the specific clinical characteristics of the patient identified by the triage nurse. However, a consistent approach to triage education and uniform triage guidelines has been repeatedly identified as a key factor in improving the consistency of application of the ATS. Physiological data demonstrates the highest degree of objectivity and consistency and research has shown that physiological observations are useful and measurable indicators of clinical urgency and patient safety. This paper will discuss the development of these discriminators as part of the educational strategy including a critique of other approaches to triage decision-making and a review of the consultative processes used to facilitate consensus amongst triage nurses, ED Nurse Managers and ED Nurse Educators. The physiological discriminators developed by this project are also presented.

Ontogeny of oxygen stores and physiological diving capability in Australian sea lions

1.For air-breathing animals in aquatic environments, foraging behaviours are often constrained by physiological capability. The development of oxygen stores and the rate at which these stores are used determine juvenile diving and foraging potential.
2. We examined the ontogeny of dive physiology in the threatened Australian sea lion Neophoca cinerea. Australian sea lions exploit benthic habitats; adult females demonstrate high field metabolic rates (FMR), maximize time spent near the benthos, and regularly exceed their calculated aerobic dive limit (cADL). Given larger animals have disproportionately greater diving capabilities; we wanted to determine the extent physiological development constrained diving and foraging in young sea lions.
3. Ten different mother/pup pairs were measured at three developmental stages (6, 15 and 23 months) at Seal Bay Conservation Park, Kangaroo Island, South Australia. Hematocrit (Hct), haemoglobin (Hb) and plasma volume were analyzed to calculate blood O2 stores and myoglobin was measured to determine muscle O₂. Additionally, FMR's for nine of the juveniles were derived from doubly-labelled water measurements.
4. Australian sea lions have the slowest documented O₂ store development among diving mammals. Although weaning typically occurs by 17·6 months, 23-month juveniles had only developed 68% of adult blood O₂. Muscle O₂ was the slowest to develop and was 60% of adult values at 23 months.
5. We divided available O₂ stores (37·11 ± 1·49 mL O₂ kg−1) by at-sea FMR (15·78 ± 1·29 mL O₂ min−1 kg−1) to determine a cADL of 2·33 ± 0·24 min for juvenile Australian sea lions. Like adults, young sea lions regularly exceeded cADL's with 67·8 ± 2·8% of dives over theoretical limits and a mean dive duration to cADL ratio of 1·23 ± 0·10.
6. Both dive depth and duration appear impacted by the slow development of oxygen stores. For species that operate close to, or indeed above their estimated physiological maximum, the capacity to increase dive depth, duration or foraging effort would be limited. Due to reduced access to benthic habitat and restricted behavioural options, young benthic foragers, such as Australian sea lions, would be particularly vulnerable to resource limitation.

The physiological and behavioural development of diving in Australian fur seal (Arctocephalus pusillus doriferus) pups

The physiological and behavioural development of diving was examined in Australian fur seal (Arctocephalus pusillus doriferus) pups to assess whether animals at weaning are capable of exploiting the same resources as adult females. Haematocrit, haemoglobin and myoglobin contents all increased throughout pup development though total body oxygen stores reached only 71% of adult female levels just prior to weaning. Oxygen storage components, however, did not develop at the same pace. Whereas blood oxygen stores had reached adult female levels by 9 months of age, muscle oxygen stores were slower to develop, reaching only 23% of adult levels by this age. Increases in diving behaviour corresponded to the physiological changes observed. Pups spent little time (<8%) in the water prior to moulting (age 1–2 months) whereas following the moult, they spent >27% of time in the water and made mid-water dives (maximum depth 35.7 ± 2.9 m) with durations of 0.35 ± 0.03 min. By 9 months (just prior to weaning), 30.5 ± 9.3% of all dives performed were U-shaped benthic dives (maximum depth 65.0 ± 6.0 m) with mean durations of 0.87 ± 0.25 min, significantly shorter than those of adult females. These results suggest that while Australian fur seal pups approaching the age of weaning are able to reach similar depths as adult females, they do not have the physiological capacity to remain at these depths for sufficient durations to exploit them to the same efficiency.

Temporal dynamics of oocyte development, plasma sex steroids and somatic energy reserves during seasonal ovarian maturation in captive Murray cod Maccullochella peelii peellii

The temporal dynamics of oocyte growth, plasma sex steroids and somatic energy stores were examined during a 12 month ovarian maturation cycle in captive Murray cod Maccullochella peelii peelii under simulated natural photothermal conditions. Ovarian function was found to be relatively uninhibited in captivity, with the exception that post-vitellogenic follicles failed to undergo final maturation, resulting in widespread pre-ovulatory atresia. Seasonal patterns of oocyte growth were characterised by cortical alveoli accumulation in March, deposition of lipids in April, and vitellogenesis between May and September. Two distinct batches of vitellogenic oocytes were found in Murray cod ovaries, indicating a capacity for multiple spawns. Plasma profiles of 17β-oestradiol and testosterone were both highly variable during the maturation period suggesting that multiple roles exist for these steroids during different stages of oocyte growth. Condition factor, liver size and visceral fat stores were all found to increase prior to, or during the peak phase of vitellogenic growth. Murray cod appear to strategically utilise episodes of high feeding activity to accrue energy reserves early in the reproductive cycle prior to its deployment during periods of rapid ovarian growth.

Does elite competition inhibit growth and delay maturation in some gymnasts? quite possibly

Today, elite young gymnasts undertake training programs of progressive volume and intensity from an early age. For example, talented young female gymnasts often commence training at age 5 or 6 and train more than 20 to 30 hours per week year-round throughout childhood and adolescence. Despite the "normal" short stature of top-level gymnasts and the obvious health benefits of physical activity during growth, there is concern that elite level or those gymnasts involved in heavy training regimens may be at risk for adverse effects on growth and maturation. This concern has been the source of much debate in the literature and is complicated by the difficulties in distinguishing between the genetic predisposition to short stature and late or delayed maturation, and the effect of environmental factors such as nutrition and exercise that may influence growth and maturation. The effect of gymnastics training on growth and maturation is often reported as averaged data: an approach that does not identify individual growth patterns. Finding no difference between groups is not proof that there is "in fact" no difference. Accepting the null hypothesis without the appropriate critical review of both the methodological and statistical power to detect differences is a flawed endeavor. We believe there is compelling "circumstantial" evidence to build a case that preparation for advanced gymnastics competition may place some children and youth at risk of reduced growth and delayed maturation.

A comparison of self-reported puberty using the pubertal development scale and the sexual maturation scale in a school-based epidemiologic survey

Purpose: To examine concordance between two self-reported measures of puberty: Sexual Maturatiom Scale (SMS) and Pubertal Developl1!ent Scale (PDS) and their acceptability to adolescents. Methods: Participants of a school-based study in grades 5, 7 and 9 were classified into one of 5 pubertal stages using each method. Results: 2864 students (age 9-16 years) participated. Agreement was moderate for males (K 0.42, 95% CI 0.39,0.45) and females (K 0.57, 95% CI 0.53, 0.61). Concordance within one stage was excellent (females 97%, males 89%), with discrepancies due to females being classified one stage later on the PDS (26%) and males one stage earlier (32%). There were more missing data for the SMS (13%) than the PDS (4%).

Sexing accuracy and indicators of maturation status in captive Murray cod Maccullochella peelii peelii using non-invasive ultrasonic imagery

Macroscopic- and histological-based assessments of gonad condition were compared with ultrasound images to determine the feasibility of this technology as a non-invasive diagnostic tool for identifying sex and assessing maturation status of Murray cod. Four age-classes (1⁺, 2⁺, 3⁺ and 6⁺ years), were sub-sampled at monthly intervals throughout their annual reproductive cycle and scanned with a 5 MHz linear transducer. An interpretation of sex was made from the resulting images and maximum cross-sectional gonad diameter and area were recorded. Fish were subsequently dissected to confirm gender, and the weights and maturation status of gonads determined and then compared with their respective image profile. Ovaries of females were usually a distinctive feature in ultrasound images, being particularly obvious in older and/or more developed fish. In contrast, the identification of male testis was more problematic. Nonetheless, identifying sex from ultrasound images was consistently achieved by recording the presence/absence of a female ovary (96% total sexing accuracy). Maximum cross-sectional ovary diameter and area were highly correlated with gonad weight (r² = 0.90 and 0.89, respectively) suggesting that indices of maturation status, comparable to the gonadosomatic index (GSI), can be obtained non-destructively from ultrasound scans of females. A less distinct relationship occurred between these dimensions and weight of testes (r² = 0.41). Significant increases (P < 0.05) in mean gonad index (GI, calculated from gonad diameter) occurred for most gonad development stages. However, differences in mean GI between maturation stages were confounded by phenotypic variability, indicating that GI may be limited to population level studies. Nevertheless, ultrasound images of ovaries at each development stage were visually distinctive and enabled qualitative evaluations of maturity, thereby complementing quantitative GI assessments. Repeated serial-monitoring of the same population using ultrasound appears to have great potential for tracking maturation-induced changes in broodfish.

Physiological, morphological and behavioural effects of selecting zebra finches for divergent levels of corticosterone

The effects of environmental stress on the physiology and behaviour of higher vertebrates has become an important avenue of research in recent years. Evidence from recent studies has suggested that the avian stress-related hormone corticosterone (CORT) may play a role in immunocompetence and sexual selection. We tested whether CORT is immunosuppressive by studying humoral and cell-mediated immune responses in populations of captive zebra finches selected for divergent peak levels of CORT. We also investigated whether selection for peak CORT has an effect on the quality of several sexually selected regions of the male zebra finch; in addition we compared morphometric parameters and the dominance ranking in males from the different selection lines. We also tested whether different components of the immune system compete for limited resources. We found that selection for divergent levels of peak CORT had little effect on humoral immunity, male sexual signal quality or dominance ranking. However, contrary to expectations, we did find a positive relationship between CORT titre and cell-mediated immunity, as well as a greater cell-mediated response in the birds selected for high CORT titre than those selected for low CORT titre. Consistent with predictions, significant negative relationships were found between both testosterone and CORT titre on humoral immunity. Birds from the low CORT lines were significantly larger in terms of skeletal size than those from the high CORT lines. Overall, our results suggest that the cell-mediated immune response is associated with a reduction in the humoral response, but only in males, and that there is no simple relationship between peak CORT levels and immune function.

The effect of acute fenitrotion exposure on a variety of physiological indices, including avian aerobic metabolism during exercise and cold exposure

The effect of fenitrothion exposure on birds was examined by measuring aerobic metabolism, blood hemoglobin content, plasma cholinesterases, and body weight for up to 21 d postdose. Peak metabolic rate was measured in a flight chamber in three-dose groups of house sparrows (Passer domesticus; 100 mg/kg = high, 60 mg/kg = medium, 30 mg/kg = low) and one-dose groups of zebra finches (Taeniopygia guttata; 3 mg/kg) and king quails (Coturnix chinensis; 26 mg/kg). Aerobic metabolism was measured during 1 h of exposure to subfreezing thermal conditions in low-dose house sparrows and king quails (26 mg/kg). Fenitrothion had no effect on metabolic rate during cold exposure or on blood hemoglobin at any time. By contrast, aerobic performance during exercise in sparrows was reduced by 58% (high), 18% (medium), and 20% (low), respectively, 2 d postdose. House sparrows (high) had the longest recovery period for peak metabolic rate (21 d) and plasma cholinesterase activity (14 d). House sparrows (high) and treated king quails had significantly lower myoglobin at 48 h postdose, whereas myoglobin was invariant in zebra finches and house sparrows (medium and low). Cholinesterase was maximally inhibited at 6 h postdose, and had recovered within 24 h, in house sparrows (low), king quails, and zebra finches. Exercise peak metabolic rate in zebra finches and king quails was reduced by 23% at 2 d and 3 d, respectively, despite these birds being asymptomatic in both behavior and plasma cholinesterase activities.

Frequency-dependent physiological trade-offs between competing colour morphs

Evolutionary theory suggests that alternative colour morphs (i.e. genetically controlled phenotypes) may derive similar fitness under frequency-dependent selection. Here we experimentally demonstrate opposing effects of frequency-dependent social environments on plasma hormone levels (testosterone and corticosterone) and immune function between red- and black-headed male morphs of the Gouldian finch (Erythrura gouldiae). Red-headed males are highly sensitive to changes in the social environment, especially towards the relative density of their own aggressive morph, exhibiting high stress responses and immunosuppression in socially competitive environments. In contrast, the non-aggressive black-headed males follow a more passive strategy that appears to buffer them against social stresses. The differential effect of hormones on aggressive behaviour and immune performance reinforces the contrasting behavioural strategies employed by these colour morphs, and highlights the importance of the social environment in determining the individual basis of behavioural and physiological responses.