Leptin receptor signaling and the regulation of mammalian physiology.

The adipocyte-derived hormone, leptin, signals the status of body energy stores to the central nervous system to regulate appetite and energy expenditure. A specific long-form leptin receptor (LepRb), a type I cytokine receptor, mediates leptin action on LepRb-expressing neurons in the brain. Leptin binding to LepRb activates the associated Janus kinase-2 (Jak2) tyrosine kinase to promote the phosphorylation of Jak2 and three residues on LepRb; each of these sites mediates a distinct aspect of downstream LepRb signaling, with differing physiologic functions. Tyr(1138) --> STAT3 signaling suppresses feeding, but is not required for a number of other leptin actions. Tyr(985) binds SH2-containing tyrosine phosphatase-2 and suppressor of cytokine signaling-3 and primarily mediates the attenuation of LepRb signaling in vivo. The role for Tyr(1077), the major regulator of signal transducer and activator of transcription-5 (STAT5) during leptin signaling, in the physiologic response to leptin remains unclear, although the obese phenotype of animals deleted for STAT5 in the brain suggests the potential importance of this signaling pathway. Leptin also modulates a number of other signaling pathways in the brain, including PI 3-kinase, mammalian target of rapamycin and AMP-dependent protein kinase; the pathways by which leptin controls these signals remain unclear, however, and may involve some indirect mechanisms. Important issues regarding leptin action and LepRb signaling in the future include not only the more thorough analysis of intracellular signaling pathways, but the neural substrate by which leptin acts, as most major populations of LepRb neurons remain poorly studied.

Estimating the date of bone remains: a multivariate study.

In previous works we have studied the time of death of bone residuals through the following parameters: total lipids, triglicerides , cholesterol, free fatty acids, total proteins, zinc, iron, manganese, and phosphorus. These elements were quantified in groups of recent bones of 1 and 2 years and of 10, 15, 18, and 20 years postmortem. In this present work we are putting these results under statistical analysis consisting of a stepwise regression. This program selects and introduces in the regression the element that shows the highest correlation with the time of death. In successive steps the partial correlations between the date and the elements not already included in the regression are studied, while keeping the effects of the elements already included fixed. As a result we put forward three formulas in which the time of death appears linked with the parameters that define it best. In the first the time of death of the bones Y is estimated according to the protein X1 Y = 40.0014 - 7. 4275X1 In the second formula the time of death Y, is estimated according to proteins X1 and triglicerides X2. Y = 45.5970 - 10. 8096X1 + 0. 4104X2 And in the third formula the time of death Y is estimated according to proteins X1, triglicerides X2, and cholesterol X3. Y = 52.2032 - 7. 8213X1 + 0. 6355X2 - 3.4930 In the three formulas the coefficients of the correlation between the time of death and the variables are improved when the logarithms of the variables are taken, instead of the original measurements.

PCB metabolism in rats following prolonged exposure to Aroclor 1242 and aroclor 1016.

Several mono- and dihydroxy metabolites of di-, tri, and tetrachlorobiphenyl have been identified in the urine of rats fed prolonged diets of Aroclor 1016 or Aroclor 1242. Combined gas chromatography-mass spectrometry was used for characterization of the metabolic products.