Interaction of the Akt substrate, AS160, with the glucose transporter 4 vesicle marker protein, insulin-regulated aminopeptidase

Insulin-regulated aminopeptidase (IRAP), a marker of glucose transporter 4 (GLUT4) storage vesicles (GSVs), is the only protein known to traffic with GLUT4. In the basal state, GSVs are sequestered from the constitutively recycling endosomal system to an insulin-responsive, intracellular pool. Insulin induces a rapid translocation of GSVs to the cell surface from this pool, resulting in the incorporation of IRAP and GLUT4 into the plasma membrane. We sought to identify proteins that interact with IRAP to further understand this GSV trafficking process. This study describes our identification of a novel interaction between the amino terminus of IRAP and the Akt substrate, AS160 (Akt substrate of 160 kDa). The validity of this interaction was confirmed by coimmunoprecipitation of both overexpressed and endogenous proteins. Moreover, confocal microscopy demonstrated colocalization of these proteins. In addition, we demonstrate that the IRAP-binding domain of AS160 falls within its second phosphotyrosine-binding domain and the interaction is not regulated by AS160 phosphorylation. We hypothesize that AS160 is localized to GLUT4-containing vesicles via its interaction with IRAP where it inhibits the activity of Rab substrates in its vicinity, effectively tethering the vesicles intracellularly.

Maternal 25-Hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size

Context: There is inconsistent evidence that maternal 25-hydroxyvitamin D [25-(OH)D] deficiency may impair fetal growth.

Objective: The objective of the study was to examine the relationship between maternal 25-(OH)D and PTH concentrations at less than 16 and 28 wk gestation and offspring birth size.

Design: This was an observational study.

Setting: The study was set at a hospital antenatal clinic.

Participants: Women with singleton pregnancies, before 16 wk gestation, participated.

Interventions: No interventions were used.

Main Outcome Measure: Knee-heel length at birth was the main outcome measure.

Results: Altogether 374 of 475 (79%) women completed this study. We found no evident relationship between birth size measures and maternal 25-(OH)D or PTH at recruitment (∼11 wk). Gestation length was 0.7 wk (95% confidence interval −1.3, −0.1) shorter and knee-heel length was 4.3 mm smaller (−7.3, −1.3) in infants of 27 mothers with low 25-(OH)D (<28 nmol/liter) at 28–32 wk vs. babies whose mothers had higher concentrations. This latter difference was reduced to −2.7 mm (−5.4, −0.1) after adjustment for gestation length, suggesting some of the apparent growth deficit is explained by shorter gestation. There was no evidence that other birth measures were affected. Maternal PTH concentration at 28–32 wk was positively related to knee-heel length, birth weight, and mid-upper arm and calf circumferences. These associations were independent of 25-(OH)D concentration.

Conclusions: Low maternal 25-(OH)D in late pregnancy is associated with reduced intrauterine long bone growth and slightly shorter gestation. The long-term consequences for linear growth and health require follow-up. The positive relationship between maternal PTH and measures of infant size may relate to increased mineral demands by larger babies, but warrants further investigation.

Serum leptin levels are associated with bone mass in nonobese women

Both serum leptin and bone mineral density are positively correlated with body fat, generating the hypothesis that leptin may be a systemic and/or local regulator of bone mass. We investigated 214 healthy, nonobese Australian women aged 20-91 yr. Bone mineral content, projected bone area, and body fat mass were measured by dual energy x-ray absorptiometry and fasting serum leptin levels by RIA. Associations between bone mineral content (adjusted for age, body weight, body fat mass, and bone area) and the natural logarithm of serum leptin concentrations were analyzed by multiple regression techniques. There was a significant positive association at the lateral spine, two proximal femur sites (Ward's triangle and trochanter), and whole body (partial r² = 0.019 to 0.036; all P < 0.05). Similar trends were observed at the femoral neck and posterior-anterior-spine. With bone mineral density the dependent variable (adjusted for age, body weight, and body fat mass), the association with the natural logarithm of leptin remained significant at the lateral spine (partial r² = 0.030; P = 0.011), was of borderline significance at the proximal femur sites (partial r² = 0.012 to 0.017; P = 0.058 to 0.120), and was not significant at the other sites. Our results demonstrate an association between serum leptin levels and bone mass consistent with the hypothesis that circulating leptin may play a role in regulating bone mass.

Differential involvement of rat medial prefrontal cortex dopamine receptors in modulation of hypothalamic- pituitary-adrenal axis responses to different stressors

Recent investigations have implicated the medial prefrontal cortex (mPFC) in modulation of subcortical pathways that contribute to the generation of behavioural, autonomic and endocrine responses to stress. However, little is known of the mechanisms involved. One of the key neurotransmitters involved in mPFC function is dopamine, and we therefore aimed, in this investigation, to examine the role of mPFC dopamine in response to stress in Wistar rats. In this regard, we infused dopamine antagonists SCH23390 or sulpiride into the mPFC via retrodialysis. We then examined changes in numbers of cells expressing the c-fos immediate-early gene protein product, Fos, in subcortical neuronal populations associated with regulation of hypothalamic-pituitary-adrenal (HPA) axis stress responses in response to either of two stressors; systemic injection of interleukin-1β, or air puff. The D1 antagonist, SCH23390, and the D2 antagonist, sulpiride, both attenuated expression of Fos in the medial parvocellular hypothalamic paraventricular nucleus (mpPVN) corticotropin-releasing factor cells at the apex of the HPA axis, as well as in most extra-hypothalamic brain regions examined in response to interleukin-1β. By contrast, SCH23390 failed to affect Fos expression in response to air puff in any brain region examined, while sulpiride resulted in an attenuation of the air puff-induced response in only the mpPVN and the bed nucleus of the stria terminalis. These results indicate that the mPFC differentially processes the response to different stressors and that the two types of dopamine receptor may have different roles.

Fouling in reverse osmosis (RO) membrane in water recovery from secondary effluent : a review

Reverse osmosis (RO) is the most preferable process for water recovery from secondary effluent (SE) because of its higher rejection of impurities with lower associated cost and higher quality of product. Fouling still is a major challenge during the water recovery due to higher contaminant loadings in SE and high rejection capability of this membrane. The presence of suspended solids, colloidal and organic matters, and high level of biological activities in SE further elevate fouling potentiality. This review was performed to identify major foulants causing hindrance in sustainable application of reverse osmosis and to present available pre-treatment options for these foulants. There are four fouling types present in RO namely; bio-fouling, inorganic/scaling, organic, and particulate fouling. Among them; bio-fouling is less understood but dominant since the pre-treatment options are not well developed. Other fouling mechanisms have been overcome by well developed pre-treatments. The major foulants for RO are dissolved and macromolecular organic substances, sparingly soluble inorganic compounds, colloidal and suspended particles, and micro-organisms. Some of these potential fouling water quality parameters (PFWQPs) are interrelated with each others such as electrical conductivity is a surrogate measure of total dissolved solids with established stable relationship. Most of these PFWQPs such as total suspended solids, turbidity, chemical oxygen demand can be removed by conventional pre-treatment; some such as colloidal particles and micro-organisms by modern options and even others such as endocrine disrupting compounds, pharmaceutical and personal care products are still challenging for current pre-treatments. These foulants need to be identified properly to integrate appropriate pre-treatments for minimizing fouling potentiality to increase water recovery at minimal costs.

Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years : results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle Study : AusDiab)

Context: Serum 25-hydroxyvitamin D [25(OH)D] concentration has been inversely associated with the prevalence of metabolic syndrome (MetS), but the relationship between 25(OH)D and incident MetS remains unclear.

Objective: We evaluated the prospective association between 25(OH)D, MetS, and its components in a large population-based cohort of adults aged 25 yr or older.

Design: We used baseline (1999–2000) and 5-yr follow-up data of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).

Participants: Of the 11,247 adults evaluated at baseline, 6,537 returned for follow-up. We studied those without MetS at baseline and with complete data (n = 4164; mean age 50 yr; 58% women; 92% Europids).

Outcome Measures: We report the associations between baseline 25(OH)D and 5-yr MetS incidence and its components, adjusted for age, sex, ethnicity, season, latitude, smoking, family history of type 2 diabetes, physical activity, education, kidney function, waist circumference (WC), and baseline MetS components.

Results: A total of 528 incident cases (12.7%) of MetS developed over 5 yr. Compared with those in the highest quintile of 25(OH)D (≥34 ng/ml), MetS risk was significantly higher in people with 25(OH)D in the first (<18 ng/ml) and second (18–23 ng/ml) quintiles; odds ratio (95% confidence interval) = 1.41 (1.02–1.95) and 1.74 (1.28–2.37), respectively. Serum 25(OH)D was inversely associated with 5-yr WC (P < 0.001), triglycerides (P < 0.01), fasting glucose (P < 0.01), and homeostasis model assessment for insulin resistance (P < 0.001) but not with 2-h plasma glucose (P = 0.29), high-density lipoprotein cholesterol (P = 0.70), or blood pressure (P = 0.46).

Conclusions: In Australian adults, lower 25(OH)D concentrations were associated with increased MetS risk and higher WC, serum triglyceride, fasting glucose, and insulin resistance at 5 yr. Vitamin D supplementation studies are required to establish whether the link between vitamin D deficiency and MetS is causal.

Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths

Objective: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification.

Methods: A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified samples of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths.

Results: Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8–78.5%) and 97.6% (96.0–99.2%), respectively; myocardial infarction 59.9% (50.9–69.0%) and 94.2% (92.4–96.0%), respectively; haemorrhagic stroke 58.9% (46.0–71.7%) and 99.8% (99.4–100.0%), respectively and; ischaemic stroke 38.7% (20.5–56.9%) and 99.9% (99.6–100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases.

Conclusions: National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively.

Covariation in life-history traits : differential effects of diet on condition, hormones, behavior, and reproduction in genetic finch morphs

The relative contribution of genetic and environmental factors in determining variation in life-history traits is of central interest to evolutionary biologists, but the physiological mechanisms underlying these traits are still poorly understood. Here we experimentally demonstrate opposing effects of nutritional stress on immune function, endocrine physiology, parental care, and reproduction between red and black head-color morphs of the Gouldian finch (Erythrura gouldiae). Although the body condition of black morphs was largely unaffected by diet manipulation, red birds were highly sensitive to dietary changes, exhibiting considerable within-individual changes in condition and immune function. Consequently, nutritionally stressed red birds delayed breeding, produced smaller broods, and reared fewer and lower-quality foster offspring than black morphs. Differences in offspring quality were largely due to morph-specific differences in parental effort: red morphs reduced parental provisioning, whereas black morphs adaptively elevated their provisioning effort to meet the increased nutritional demands of their foster brood. Nutritionally stressed genetic morphs also exhibited divergent glucocorticoid responses. Black morphs showed reduced corticosterone-binding globulin (CBG) concentrations and increased levels of free corticosterone, whereas red morphs exhibited reduced free corticosterone levels and elevated CBG concentrations. These opposing glucocorticoid responses highlight intrinsic differences in endocrine sensitivities and plasticity between genetic morphs, which may underlie the morph-specific differences in condition, behavior, and reproduction and thus ultimately contribute to the evolution and maintenance of color polymorphism.

Physiological stress responses in the warm-water fish matrinxã (Brycon amazonicus) subjected to a sudden cold shock

The present work evaluated several aspects of the generalized stress response [endocrine (cortisol), metabolic (glucose), hematologic (hematocrit and hemoglobin) and cellular (HSP70)] in the Amazonian warm-water fish matrinxã (Brycon amazonicus ) subjected to an acute cold shock. This species farming has been done in South America, and growth and feed conversion rates have been interesting. However, in subtropical areas of Brazil, where the water temperature can rapidly change, high rates of matrinxã mortality have been associated with abrupt decrease in the water temperature. Thus, we subjected matrinxã to a sudden cold shock by transferring the fish directly to tanks in which the water temperature was 10oC below the initial conditions (cold shock from 28ºC to 18oC). After 1h the fish were returned to the original tanks (28ºC). The handling associated with tank transfer was also imposed on control groups (not exposed to cold shock). While exposure to cold shock did not alter the measured physiological conditions within 1h, fish returned to the ambient condition (water at 28º C) significantly increased plasma cortisol and glucose levels. Exposure to cold shock and return to the warm water did not affect HSP70 levels. The increased plasma cortisol and glucose levels after returning the fish to warm water suggest that matrinxã requires cortisol and glucose for adaptation to increased temperature.