ABSTRACT
Embryonic craniofacial development depends on the coordinated outgrowth and fusion of multiple facial primordia, which are populated with cranial neural crest cells and covered by the facial ectoderm. Any disturbance in these developmental events, their progenitor tissues, or signaling pathways can result in craniofacial deformities such as orofacial clefts, which are among the most common birth defects in humans. In the present study, we show that Rdh10 loss of function leads to a substantial reduction in retinoic acid (RA) signaling in the developing frontonasal process during early embryogenesis, which results in a variety of craniofacial anomalies, including midfacial cleft and ectopic chondrogenic nodules. Elevated apoptosis and perturbed cell proliferation in postmigratory cranial neural crest cells and a substantial reduction in Alx1 and Alx3 transcription in the developing frontonasal process were associated with midfacial cleft in Rdh10-deficient mice. More important, expanded Shh signaling in the ventral forebrain, as well as partial abrogation of midfacial defects in Rdh10 mutants via inhibition of Hh signaling, indicates that misregulation of Shh signaling underlies the pathogenesis of reduced RA signaling-associated midfacial defects. Taken together, these data illustrate the precise spatiotemporal function of Rdh10 and RA signaling during early embryogenesis and their importance in orchestrating molecular and cellular events essential for normal midfacial development.
Subject(s)
Cleft Lip , Cleft Palate , Craniofacial Abnormalities , Animals , Cleft Lip/genetics , Cleft Palate/genetics , Craniofacial Abnormalities/genetics , Embryonic Development , Hedgehog Proteins/metabolism , Mice , Neural Crest , TretinoinABSTRACT
Feeding a high fish oil diet (25 wt%) to rats for 14 days increased the content of docosahexaenoic acid (DHA) in liver lipids, and diminished the liver antioxidant defenses as measured by the contents of alpha-tocopherol, ascorbic acid and non-protein SH, the last of which is consisting mostly of glutathione, and the activity of selenium-dependent glutathione peroxidase (GSHPx). These changes in antioxidant defenses are suggested to be associated with an increased susceptibility of the liver to lipid peroxidation as assessed by thiobarbituric acid (TBA) reaction and chemiluminescence intensity. Serum TBA value was also high in the rats given high fish oil diet. The present results demonstrate that a high fish oil diet potentiates susceptibility of rats to lipid peroxidation and augments requirement for antioxidants to provide adequate protection.
Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fish Oils/administration & dosage , Lipid Peroxidation , Liver/metabolism , Animals , Antioxidants/metabolism , Ascorbic Acid/metabolism , Docosahexaenoic Acids/metabolism , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Luminescent Measurements , Male , Rats , Rats, Sprague-Dawley , Sulfhydryl Compounds/metabolism , Thiobarbiturates/metabolism , Vitamin E/metabolismABSTRACT
Performance characteristics of several new types of photomultiplier tubes (PMT) with microchannel plates (MCP) are presented in this paper. They are the MCP-PMT with 6-microm diam channels, MCP-PMT with an S-l photocathode, and MCP-PMT with multi (discrete) anode and gatable MCP-PMT. Important requirements of an optical detector for picosecond lasers, fluorescence measurements, and material analysis are low light detectability, ultrafast time response, and versatile operation including modulation. The basic configuration, characteristics, and practical results of these detectors are described.
