Coevolution of Atomic Resolution and Whole-Brain Imaging for Tau Neurofibrillary Tangles.

Neurofibrillary tangle (NFT) imaging methods at the distinct scales of atomic and whole-brain resolutions have coevolved rapidly. Linking these two areas of research provides insight into how and why certain tau radiotracers, using positron emission tomography (PET), bind selectively to certain morphological forms of the NFT fibril. In this Review, a brief history and background for each research area is presented leading to a summary of the current state of knowledge, with a synopsis of PET NFT radiotracers and an outlook for near-term research efforts. The continued integration of information provided at the level of each of these scales of resolution will catalyze the next generation of clinical imaging technique development and enhance our interpretations of them.

Hydroxylated and sulfated metabolites of commonly occurring airborne polychlorinated biphenyls inhibit human steroid sulfotransferases SULT1E1 and SULT2A1.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that are associated with varied adverse health effects. Lower chlorinated PCBs are prevalent in indoor and outdoor air and can be metabolized to their hydroxylated derivatives (OH-PCBs) followed by sulfation to form PCB sulfates. Sulfation is also a means of signal termination for steroid hormones. The human estrogen sulfotransferase (SULT1E1) and alcohol/hydroxysteroid sulfotransferase (SULT2A1) catalyze the formation of steroid sulfates that are inactive at steroid hormone receptors. We investigated the inhibition of SULT1E1 (IC50s ranging from 7.2 nM to greater than 10 µM) and SULT2A1 (IC50s from 1.3 µM to over 100 µM) by five lower-chlorinated OH-PCBs and their corresponding PCB sulfates relevant to airborne PCB-exposure. Several congeners of lower chlorinated OH-PCBs relevant to airborne PCB exposures were potent inhibitors of SULT1E1 and SULT2A1 and thus have the potential to disrupt regulation of intracellular concentrations of the receptor-active steroid substrates for these enzymes.