SUMMARY
The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal which acts centrally to suppress the intake of “sweets.”
Risk-need assessment is widely accepted as best practice with juvenile offenders and is underpinned by a healthy research literature on risk assessment inventories. Previous studies have found both similarities and differences on risk measures when gender and racial/ethnic subgroups have been compared. Differential validity has been examined, but differential prediction has been overlooked. The current study undertook gender and ethnic comparisons for a large sample (n = 3568) of community-based juvenile offenders who were evaluated using the Australian Adaptation of the Youth Level of Service/Case Management Inventory (YLS/CMI-AA). Analyses showed various gender and ethnic differences at the item level, across domain scores and on the total inventory score, but not for validity indices. However, 1-year reoffending rates for youth in three classification categories (low, moderate, high) varied by gender and ethnicity. The findings were related to contemporary understandings of the risk factors for offending and the dynamics of crime for gender/ethnic subgroups. It is argued that in spite of these subgroup differences, a generic inventory such as the YLS/CMI-AA can be used fairly with various subgroups. Recommendations for how this could be accomplished are provided.
The plasma membranes of epithelial cells plasma membranes contain distinct apical and basolateral domains that are critical for their polarized functions. However, both domains are continuously internalized, with proteins and lipids from each intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs must faithfully recycle membrane proteins back to the correct plasma membrane domains. We examined sorting within REs and found that apical and basolateral proteins were laterally segregated into subdomains of individual REs. Subdomains were absent in unpolarized cells and developed along with polarization. Subdomains were formed by an active sorting process within REs, which precedes the formation of AP-1B-dependent basolateral transport vesicles. Both the formation of subdomains and the fidelity of basolateral trafficking were dependent on PI3 kinase activity. This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity.
This study examined the predictive validity of the Australian Adaptation of the Youth Level of Service/Case Management Inventory (YLS/CMI-AA). The focus was on the subcomponents of the inventory, which represent one static and seven dynamic risk-need domains. Reoffending outcomes within 1 year of the inventory were obtained for a large sample (N = 3,568) of young people under juvenile justice supervision in the community. Logistic regression analyses investigated the relative contribution of YLS domain scores. The results showed that the static and four dynamic domain scores independently predicted recidivism and that the combination of those domain scores yielded a small improvement in prediction. A similar pattern of results was obtained from analyses of the simple additive scores for the YLS domains. The findings support the YLS/CMI-AA total score as a sufficiently useful predictor of risk, and they clarify the contribution of static and dynamic risk components.
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