Frontiers in Endocrinology
Differential roles of orexin receptors in the regulation of sleep/wakefulness
Takeshi Sakurai, the lead author on the 1998 article that first described orexin, here reviews the latest research on orexin and its role in regulating sleep and wakefulness.
The sleep cycle of mammals is partly regulated by the neuropeptide orexin, which is exclusively produced in the hypothalamus and from there travels to other parts of the nervous system. Wakefulness tends to increase when orexin binds to specific receptors in the brain and brain stem. Loss of orexin-producing nerve cells or mutations that disrupt the orexin gene or its receptor genes can cause narcolepsy, a disorder of humans and other mammals, whose main symptom is that patients suddenly and involuntarily fall asleep several times per day.
Sakurai and colleagues show that the expression of the two orexin receptor genes throughout the nervous system is a complex mosaic, while the effects of orexin are tissue-specific and poorly understood. A further complication is that orexin also plays an important role in regulating appetite, mood, and metabolism. Despite these complications, the orexin pathway is a promising avenue for treating sleep disorders.
Frontiers in Microbiology
Reclaimed water as a reservoir of antibiotic resistance genes: distribution system and irrigation implications
Bacteria evolve faster than other organisms, partly because bacterial populations grow fast and hold enormous genetic diversity, and partly because many bacteria are capable of sharing their genes with each other, for example, genes that confer resistance against antibiotics. Amy Pruden and colleagues from Virginia Tech tested recycled wastewater in the western USA, and detected genes for resistance against five classes of antibiotics, with densities of up 100 million gene copies per liter.
The study emphasized the importance of testing water at the point of use, where several resistance genes were detected that were not found in water leaving the treatment plants. Since recycled wastewater is commonly used for irrigation, these genes could spread to other bacteria, in the soil or on the skin of people exposed to the water, making them likewise resistant. Genetic material from waterborne pathogenic bacteria (e.g. Legionella, which can cause Legionnaires disease) was also detected.
The presence in recycled wastewater of genes conferring resistance against vancomycin is especially cause for concern, since vancomycin is commonly used as a last-resort treatment against infections that are resistant to other antibiotics. These results call for more research to identify effective disinfection practices that destroy DNA, in addition to inactivating bacteria, and protect the distribution pipes from re-growth of antibiotic resistant bacteria.
Frontiers in Physiology
Cholesterol accelerates the binding of Alzheimer’s beta-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation
In Alzheimer’s disease, a protein called beta-amyloid binds to the cell membrane of brain cells and disrupts their function. It has long been known that lipid molecules such as ganglioside GM1 (common in the membrane of brain cells) and cholesterol contribute to the toxic effects of beta-amyloid, but the underlying mechanism remained unclear. Jacques Fantini and colleagues here use chemistry and molecular modelling to elucidate this mechanism. They describe a perfectly tuned molecular “ballet” between beta-amyloid and the membranes of brain cells. In this ballet, cholesterol initially interacts with two ganglioside GM1 molecules and forces them to group into a chalice-shaped structure, which beta-amyloid can then enter to bind to ganglioside GM1. These results thus explain the well-established, but not previously explained, association between between high cholesterol and the risk of Alzheimer’s disease. Fantini et al. suggest that a fruitful new approach for Alzheimer therapy might be to use drugs that prevent the interaction between cholesterol and ganglioside GM1.