Data from a comprehensive literature search of environmentally relevant physical-chemical properties for nine polybrominated diphenyl ethers (PBDE), ranging from a monobrominated congener to the fully brominated decabromodiphenyl ether, were evaluated and adjusted to achieve both internal and interhomologue consistency. These data were then used in four model-based long-range transport potential (LRTP) assessment methods. The models TaPL3-2.10, ELPOS-1.1.1, Chemrange-2, and Globo-POP-1.1 were found to yield comparable predictions. A comparison of the LRTP estimates for the PBDEs with those of benchmark chemicals (polychlorinated biphenyls [PCBs]) suggest that the lower-brominated congeners have a LRTP comparable to that of PCBs known to be subject to significant LRT, whereas the highly brominated congeners have a very low potential to reach remote areas. This is in agreement with field measurements in remote regions that indicate that the lighter components of commercially produced PBDE mixtures predominate. Deviations between Chemrange and the models based on the concept of a characteristic travel distance were due to differences in the assumed height of the air compartment, which influences the relative importance of atmospheric degradation and deposition processes. The three models assuming a uniform temperature of 25 degrees C may underestimate the LRTP of the smaller congeners. Only atmospheric parameters had a notable influence on the LRTP estimates by TaPL3, ELPOS, and Chemrange. whereas the relative enrichment of chemicals in the Arctic calculated by Globo-POP is additionally sensitive to the parameters related to the interaction of temperature with air-surface exchange and degradation in surface compartments.

Insulin promotes glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4). In unstimulated cells, rapid endocytosis, slow exocytosis and dynamic or static retention cause GLUT4 to concentrate in early recycling endosomes, the trans-Golgi network and vesicle-associated protein 2-containing vesicles. The coordinated action of phosphatidylinositol 3-kinase effectors, protein kinase Akt, atypical protein kinase C (aPKC) and Akt substrate of 160-kDa (AS160), regulates the GLUT4 cycle by affecting its translocation, fusion with the plasma membrane, internalization and sorting. We review the evidence that supports such cycling, evaluate current models proposing static or dynamic retention, and highlight how distinct steps of GLUT4 transport are regulated by insulin signals. In particular, fusion seems to be regulated by aPKC (via munc18) and Akt (via syntaxin4-interacting protein (synip)). AS160 participates in GLUT4 intracellular retention, and possibly fusion, through candidate ras-related GTP-binding protein (Rab)2, Rab8, Rab10 and/or Rab14. The localization of the insulin-sensitive GLUT4 compartment and the precise target of insulin-derived signals remain open for future investigation.

Insulin stimulation of glucose uptake into skeletal muscle and adipose tissues is achieved by accelerating glucose transporter GLUT4 exocytosis from intracellular compartments to the plasma membrane and minimally reducing its endocytosis. The round trip of GLUT4 is intricately regulated by diverse signaling molecules impinging on specific compartments. Here we highlight the key molecular signals that are turned on and off by insulin to accomplish this task.

Increasing evidence suggests that deficits in adult stem cell maintenance cause aberrant tissue repair and premature aging [1]. While the mechanisms regulating stem cell longevity are largely unknown, recent studies have implicated p53 and its family member p63. Both proteins regulate organismal aging [2-4] as well as survival and self-renewal of tissue stem cells [5-9]. Intriguingly, haploinsufficiency for a third family member, p73, causes age-related neurodegeneration [10]. While this phenotype is at least partially due to loss of the ΔNp73 isoform, a potent neuronal prosurvival protein [11-16], a recent study showed that mice lacking the other p73 isoform, TAp73, have perturbations in the hippocampal dentate gyrus [17], a major neurogenic site in the adult brain. These findings, and the link between the p53 family, stem cells, and aging, suggest that TAp73 might play a previously unanticipated role in maintenance of neural stem cells. Here, we have tested this hypothesis and show that TAp73 ensures normal adult neurogenesis by promoting the long-term maintenance of neural stem cells. Moreover, we show that TAp73 does this by transcriptionally regulating the bHLH Hey2, which itself promotes neural precursor maintenance by preventing premature differentiation.