Month: September 2022

TWENTY FIVE PERCENT IN COLLEGES. "About 7% of U.S. university students report having taken stimulants "nonmedically" at least once, according to a 2005 study of nearly 11,000 students. On some campuses — primarily private, élite schools — a full quarter of students admit to nonmedical drug use in the past year, mainly in an attempt to improve grades." https://lnkd.in/dJu2gyH View in LinkedIn

HIGH STRESS DRUGS. "Smart drugs are used widely off-campus as well: fighter pilots take stimulants to enhance alertness and cognition on critical missions; in the civilian world, executives take beta-blockers to calm nerves, while some time-pressed writers use wakefulness drugs, like modafinil, to meet deadlines." https://lnkd.in/dJu2gyH View in LinkedIn

WIDESPREAD USE. "Recreational Provigil user testimonials are all over the web. Not only are people able to work with little or no sleep, the drug has the advantage of spurring weight loss and some users report a general mood enhancing side effect. The U.S. military has also reportedly tested it on helicopter and F117 pilots to see if they remain effective for up to 88 hours without sleep." https://lnkd.in/di4Vpi8 View in LinkedIn

SIGNIFICANT NUMBERS AND RISING. "By the end of 2009, at least 25 studies reported surveys of college students’ rates of nonmedical stimulant use. Of the studies using relatively smaller samples, prevalence was, in chronological order, 16.6% (lifetime); 35.3% (past year;), 13.7% (lifetime;), 9.2% (lifetime;), and 55% (lifetime, fraternity students only." https://lnkd.in/deytSnW View in LinkedIn

FRAGMENT FROM NATURE this weekend is a historical vignette on the discovery of nuclear receptors in cells, based on a lovely 2014 review by Ronald Evans and David Mangelsdorf. The gene isolation of nuclear receptors led to the discovery of receptors without known function, so-called “orphan receptors” which eventually were assigned to functional pathways. Importantly, these orphan receptors belonged to large conserved superfamilies. This was effectively the start of molecular endocrinology, a far-reaching discipline that had a big impact on medicine. View in LinkedIn

STARTING WITH GENES. “Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors.” https://lnkd.in/dXjCCgQ View in LinkedIn

THEN CAME THE ORPHANS. “This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid X receptor (RXR) positioned nuclear receptors at the epicenter of the “Big Bang” of molecular endocrinology.” https://lnkd.in/dXjCCgQ View in LinkedIn

CASCADE REACTIONS. “Steroid and thyroid hormones, along with vitamins A and D, were elucidated based on their endocrine origin and the physiologic processes that they regulate. Each of these small molecules is chemically distinct, and although there was initially no presumption that they might have a shared signaling mechanism, initial biochemical experiments revealed the presence of an intracellular receptor that, upon ligand addition, activated transcription of tissue-specific sets of target genes.” https://lnkd.in/dXjCCgQ View in LinkedIn

METHODOLOGICAL LIMITATIONS. “The idea of a “Nuclear Receptor” that could directly translate simple chemical changes into distinct physiologic effects persisted for several decades, but the fundamental nature of this receptor, its means for recognizing specific chemical ligands, its mode of interaction with the genome, and its mechanism for control of gene transcription were all beyond the limits of classic biochemical analysis.” https://lnkd.in/dXjCCgQ View in LinkedIn

FIRST BIG BREAKTHROUGH. “The isolation of the first complete steroid receptor cDNAs, the glucocorticoid and estrogen receptors, was transformative.” https://lnkd.in/dXjCCgQ View in LinkedIn