Saint Louis University

About: Saint Louis University is a education organization based out in St Louis, Missouri, United States. It is known for research contribution in the topics: Population & Health care. The organization has 18927 authors who have published 34895 publications receiving 1267475 citations. The organization is also known as: SLU & St. Louis University.

A single N-terminal phosphomimic disrupts TDP-43 polymerization, phase separation, and RNA splicing

Abstract: TDP‐43 is an RNA‐binding protein active in splicing that concentrates into membraneless ribonucleoprotein granules and forms aggregates in amyotrophic lateral sclerosis (ALS) and Alzheimer9s disease Although best known for its predominantly disordered C‐terminal domain which mediates ALS inclusions, TDP‐43 has a globular N‐terminal domain (NTD) Here, we show that TDP‐43 NTD assembles into head‐to‐tail linear chains and that phosphomimetic substitution at S48 disrupts TDP‐43 polymeric assembly, discourages liquid–liquid phase separation (LLPS) in vitro , fluidizes liquid–liquid phase separated nuclear TDP‐43 reporter constructs in cells, and disrupts RNA splicing activity Finally, we present the solution NMR structure of a head‐to‐tail NTD dimer comprised of two engineered variants that allow saturation of the native polymerization interface while disrupting higher‐order polymerization These data provide structural detail for the established mechanistic role of the well‐folded TDP‐43 NTD in splicing and link this function to LLPS In addition, the fusion‐tag solubilized, recombinant form of TDP‐43 full‐length protein developed here will enable future phase separation and in vitro biochemical assays on TDP‐43 function and interactions that have been hampered in the past by TDP‐43 aggregation

Fluctuations in autonomic nervous activity during sleep displayed by power spectrum analysis of heart rate variability

Abstract: Objective The use of an efficient noninvasive method to investigate the autonomic nervous system and cardiovascular control during sleep Background Beat-to-beat heart rate variability displays two main components: a low-frequency (LF) one representing sympathetic and parasympathetic influence and a high-frequency (HF) component of parasympathetic origin Sympathovagal balance can be defined as LF/HF ratio Methods/design We reviewed normal, standardly staged all-night polysomnograms from 10 healthy children aged 6 to 17 years Recorded 256-second traces of heart rate and respiration were sampled Power spectra of instantaneous heart rate and respiration were computed using a fast Fourier transform method Results The study revealed a decrease in LF during sleep, with minimal values during non-REM slow-wave sleep and elevated levels similar to those of wakefulness during REM HF increased with sleep onset, reaching maximal values during slow-wave sleep, and behaved as a mirror image of LF LF/HF ratio displayed changes similar to those in LF Conclusion The sympathetic predominance that characterizes wakefulness decreases during non-REM sleep, is minimal in slow-wave sleep, and surges toward mean awake levels during REM sleep The autonomic balance is shifted toward parasympathetic predominance during slow-wave sleep This noninvasive method used to outline autonomic activity achieves results that are in complete agreement with those obtained with direct invasive tools

Hepcidin: a putative iron-regulatory hormone relevant to hereditary hemochromatosis and the anemia of chronic disease.

Abstract: Disorders of iron homeostasis, resulting in iron deficiency or overload, are very common worldwide (1). Normal iron homeostasis depends on a close link between dietary iron absorption and body iron needs (2). The paper by Nicolas et al. in this issue of PNAS (3) presents the exciting possibility that a central player in the communication of body iron stores to the intestinal absorptive cells may have been identified. This unlikely player, originally identified as a circulating antimicrobial peptide, is the hepatic protein hepcidin. Nicolas et al. found absence of hepcidin expression in mice exhibiting iron overload consequent to targeted disruption of the gene encoding the transcription factor Upstream Stimulatory Factor 2 (USF2). Nicolas et al. present the exciting possibility that a central player in the communication of body iron stores to the intestinal absorptive cells may have been identified.