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Hypocretin-1 and 2 (or orexin A and B) are neuropeptides exclusively produced by a group of neurons in the lateral and dorsomedial hypothalamus that project throughout the brain. In accordance with this, the two different hypocretin receptors are also found throughout the brain. The hypocretin system is mainly involved in sleep-wake regulation, but also in reward mechanisms, food intake and metabolism, autonomic regulation including thermoregulation, and pain. The disorder most strongly linked to the hypocretin system is the primary sleep disorder narcolepsy type 1 caused by a lack of hypocretin signaling, which is most likely due to an autoimmune process targeting the hypocretin-producing neurons. However, the hypocretin system may also be affected, but to a lesser extent and less specifically, in various other neurological disorders. Examples are neurodegenerative diseases such as Alzheimer's, Huntington's and Parkinson's disease, immune-mediated disorders such as multiple sclerosis, neuromyelitis optica, and anti-Ma2 encephalitis, and genetic disorders such as type 1 diabetus mellitus and Prader-Willi Syndrome. A partial hypocretin deficiency may contribute to the sleep features of these disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that aberrant structure and function of the COL4A1 protein may also be a significant factor in modulating immunity.

Recent data from clinical and mammalian genetic studies indicate that COL4A1 mutations manifest with basement membrane defects that result in muscle weakness, cramps, contractures, dystrophy and atrophy. In-depth studies of mutant COL4A1-associated muscle phenotype, however, are lacking and significant details of the muscle-specific pathomechanisms remain unknown. In this study, we have used a comprehensive set of Drosophila col4a1 and col4a2 mutants and a series of genetic and mutational analyses, gene, protein expression, and immunohistochemistry experiments in order to establish a Drosophila model and address some of these questions. The Drosophila genome contains two type IV collagen genes, col4a1 and col4a2. Mutant heterozygotes of either gene are viable and fertile, whereas homozygotes are lethal. In complementation analysis of all known mutants of the locus and a complementation matrix derived from these data we have identified the dominant lesions within the col4a1, but not within the col4a2 gene. Expression of a col4a1 transgene partially rescued the dominant and recessive mutant col4a1 alleles but not the col4a2 mutations that were all recessive. Partial complementation suggested that col4a1 gene mutations have strong antimorph effect likely due to the incorporation of the mutant protein into the triple helix. In col4a1 mutants, morphological changes of the oviduct muscle included severe myopathy with centronuclear myofibers leading to gradual development of female sterility. In larval body wall muscles ultrastructural changes included disturbance of A and I bands between persisting Z bands. In the most severely affected DTS-L3 mutant, we have identified four missense mutations within the coding region of the col4a1 gene two of which affected the Y within the Gly-X-Y unit and a 3' UTR point mutation. In conclusion, our Drosophila mutant series may serve as an effective model to uncover the mechanisms by which COL4A1 mutations result in compromised myofiber-basement membrane interactions and aberrant muscle function., (Copyright © 2011 International Society of Matrix Biology. All rights reserved.)

The ubiquity of television in American culture makes it a potential contributor to the obesogenic (obesity-causing) environment. Televised food advertisements, which encourage viewers to eat the foods promoted for sale, constitute a de facto set of dietary endorsements. The purpose of this study was to compare the nutritional content of food choices endorsed on television to nutritional guidelines. Using a cross-sectional design, food advertisements were observed during 84 hours of primetime and 12 hours of Saturday-morning televised broadcast during the fall of 2004. One-sample t tests were used to compare the food group servings of observed food items to the recommended daily servings and to compare the nutrient content of observed food items to the Daily Values. Results suggest that a diet consisting of observed food items would provide 2,560% of the recommended daily servings for sugars, 2,080% of the recommended daily servings for fat, 40% of the recommended daily servings for vegetables, 32% of the recommended daily servings for dairy, and 27% of the recommended daily servings for fruits. The same diet would substantially oversupply protein, total fat, saturated fat, cholesterol, and sodium, while substantially undersupplying carbohydrates, fiber, vitamins A, E, and D, pantothenic acid, iron, phosphorous, calcium, magnesium, copper, and potassium. Overall, the food choices endorsed on television fail to meet nutrition guidelines and encourage nutritional imbalance., (2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

An endonuclease-free, protoplast-forming enzyme complex was prepared from the "snail enzyme." The purified preparation has high protoplast-forming activity comparable to the crude enzyme complex without destroying circular plasmid DNA. Furthermore, a higher transformation rate was achieved by the application of the endonuclease-free enzyme complex in both yeast and filamentous fungal vector-host systems.