Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration

Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells are derived from pancreatic ducts but the regulatory factors involved are still largely unknown. Here, we show that the zebrafish sox9b gene is expressed in pancreatic ducts where it labels the pancreatic Notch-responsive cells previously shown to be progenitors. Inactivation of sox9b disturbs duct formation and impairs regeneration of beta cells from these ducts in larvae. sox9b expression in the midtrunk endoderm appears at the junction of the hepatic and ventral pancreatic buds and, by the end of embryogenesis, labels the hepatopancreatic ductal system as well as the intrapancreatic and intrahepatic ducts. Ductal morphogenesis and differentiation are specifically disrupted in sox9b mutants, with the dysmorphic hepatopancreatic ducts containing misdifferentiated hepatocyte-like and pancreatic-like cells. We also show that maintenance of sox9b expression in the extrapancreatic and intrapancreatic ducts requires FGF and Notch activity, respectively, both pathways known to prevent excessive endocrine differentiation in these ducts. Furthermore, beta cell recovery after specific ablation is severely compromised in sox9b mutant larvae. Our data position sox9b as a key player in the generation of secondary endocrine cells deriving from pancreatic ducts in zebrafish.     

Cannabinoid Receptor Type 1 Protects against Age- Related Osteoporosis by Regulating Osteoblast and Adipocyte Differentiation in Marrow Stromal Cells

Age-related osteoporosis is characterized by reduced bone formation and accumulation of fat in the bone marrow compartment. Here, we report that the type 1 cannabinoid receptor (CB1) regulates this process. Mice with CB1 deficiency (CB1^−/−) had increased peak bone mass due to reduced bone resorption, but developed age-related osteoporosis with reduced bone formation and accumulation of adipocytes in the bone marrow space. Marrow stromal cells from CB1^−/− mice had an enhanced capacity for adipocyte differentiation, a reduced capacity for osteoblast differentiation, and increased expression of phosphorylated CREB (pCREB) and PPARγ. Pharmacological blockade of CB1 receptors stimulated adipocyte differentiation, inhibited osteoblast differentiation, and increased cAMP and pCREB in osteoblast and adipocyte precursors. The CB1 receptor is therefore unique in that it regulates peak bone mass through an effect on osteoclast activity, but protects against age-related bone loss by regulating adipocyte and osteoblast differentiation of bone marrow stromal cells.     

Modification of bovine pancreatic ribonuclease A with pyridoxal 5'-phosphate. Isolation and identification of derivatives.

Bovine pancreatic ribonuclease A was allowed to react with pyridoxal 5'-phosphate at pH 8 and 4 degrees. After reduction with sodium borohydride, the principal products formed in the initial stages of modification were separated by successive chromatography on CM-cellulose and SP-Sephadex. The isolated derivatives were identified as Nalpha-(P-pyridoxyl)-Lys-1-,Nepsilon-(P-pyridoxyl)-Lys-7-, and Nepsilon-(P-pyridoxyl)-Lys-41-ribonuclease A. These results are interpreted in terms of the specificity of pyridoxal-P as a protein reagent.     

The retino-hypothalamic tract is involved in prolactin regulation in fetal sheep.

To investigate the role of the retino-hypothalamic tract on fetal prolactin regulation, we examined the effect of ocular enucleation on fetal plasma prolactin. Eleven fetuses of Suffolk ewes were chronically catheterized during fall, and six of them were subjected to bilateral ocular enucleation. All ewes were kept at 12h:12h light:dark cycle (lights on at 0800 and off at 2000). The experiments were performed 5-9 days after surgery (GA control fetuses 125 +/- 1.5, optical enucleation 121.3 +/- 1.5 days). Blood samples were taken from fetuses hourly around the clock, and plasma prolactin and cortisol were measured by radioimmunoassay (RIA). Luteinizing hormone (LH) and Growth hormone (GH) were measured in pooled plasma samples from control and enucleated fetuses by RIA. Average plasma prolactin was 5-fold lower in enucleated than in control fetuses (9.6 +/- 0.5 and 54.2 +/- 3.3 ng/ml, SEM; P < 0.005). Both control and enucleated fetuses presented circadian rhythm of prolactin with acrophase between 1400 and 1830 h. An enucleated fetus was tested for response of prolactin to TRH. Prolactin increased as described in the literature. There was no change in plasma concentration of cortisol, LH or GH after ocular enucleation. Our data indicate that the optical pathway participates in prolactin regulation in the fetal sheep.     

Estrous behavior following prostaglandin F2α injection in Zebu cattle under continuous observation

A study was conducted to improve understanding of the behavioral aspects of Zebu cattle in estrus in the tropics. Sixteen of 26 cows in group A and 21 of 34 in group B were found to have a corpus luteum and were injected with 30 mg of prostaglandin F2α. In group B, a bull of proven libido was placed with the cows. Animals not injected were considered to be in proestrus and therefore left in the groups. Recorded sexual activity included licking and smelling the genital area, butting, following, and mounting or attemping to mount, both actively and passively. Animals were observed continuously for 100 hs. following injection. Only 56% of the injected animals in Group A and 62% in group B were found in estrus. The average number of mounts observed was 15.9 per cow during the estrous period which lasted 14.4 h. ± 5.1 (mean ± SD) for 12 cows in group A. In group B, cows mounted 13.9 times each in a period of 12.6 h. ± 5.5 (mean ± SD) for 17 animals. In both groups, the 3-hour period during which most mounting activity was recorded was from 0600 to 0900 (25% and 33% for groups A and B, respectively). However, 63% of all mounts were observed at night (1800 to 0600 hrs) in group A as were 53% in group B. No sexual activity was observed for any cow during the first 40 h. of observation. Activity started with constant butting that preceded mounting behavior. This pattern was better defined in group A than in group B where the bull was present. Although all activities were observed at some stage during the observation period, no clear relationship between mounting and other activities could be established.