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Durability of Tuberculosis Drug Increased through New Formulation
Scientists have developed a long-acting delivery system for the tuberculosis drug, rifabutin, that could increase compliance to treatment. The team combined rifabutin with biodegradable polymers and nontoxic, biocompatible solvents and injected the formulation subcutaneously in mice. The solvents solidify in the body upon injection generating an implant that enables the slow release of the drug over time. The new delivery system also allows higher loads of rifabutin in a single injection.
Optogenetics Uncovers Working Memory’s High-Dimensional Circuitry
By contrasting a working memory-dependent task where mice are rewarded upon successful matching of a visual stimulus to one seen earlier, and a working memory-independent task, with identical delay, stimuli, and rewards, scientists have characterized the metrics of how working memory is represented in neural circuits. The study provides support for a "high-dimensional" representation for the maintenance of working memory, in which dispersed cell populations encode working memory with subtle variables in firing uncorrelated to patterns of activity.
Alzheimer’s Pathology Could Benefit from Activating Microglial Targets of Rapamycin
In Alzheimer’s disease (AD) patients, rapamycin treatment could aggravate beta-amyloid related pathologies, a new mouse study indicates. Researchers show rapamycin taken orally inhibits the mTOR signaling pathway in microglial cells in the brain that regulates cell metabolism. This down-regulates a gene called Trem2. Trem2 is a receptor located on the surface of microglia that enables these cells to engulf and degrade β-amyloid. Loss of Trem2 in microglia impairs amyloid degradation, which in turn causes a buildup of β-amyloid plaques.
Sex-Specific Imprinted Genes Match Nutrient Supply to Growing Baby
Reproductive biologists at the University of Cambridge, U.K., have identified a molecular pathway that fetuses use to communicate their growing needs to the placenta, promoting its growth and ensuring an adequate nutrient supply during late pregnancy. The imprinted gene called IGF2 is needed for the growth, the authors show. The study also reveals an epigenomic tug-of-war between maternal and paternal genes that may help explain why some babies grow poorly in the womb.
Autism-Linked Immune Problems Are Caused by Maternal Gut Bacteria
Using a multi-pronged approach including immunology, germ-free models, neuroscience, and behavioral assays, a team led by scientists at Harvard Medical School and Massachusetts Institute of Technology investigated the mechanistic underpinnings of immune dysfunction in animal models of autism. The study showed changes in the gut microbiota of pregnant mice following immune activation affect chromatin accessibility in a subset of T cells in their offspring, priming them for immune activation and inflammatory attacks of the gut after birth.