The NAD-booster nicotinamide riboside potently stimulates hematopoiesis through increased mitochondrial clearance
Contributors: Olaia Naveiras
... It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD+-boosting agent Nicotinamide Riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD+ boosting strategies on the most primitive blood stem cells, establishes a novel link between HSC mitochondrial stress, mitophagy and stem cell fate decision, and unveils the potential of NR to improve recovery of patients suffering from hematological failure including post-chemo/radiotherapy.
Contributors: Nicolas Sarute, Susan R Ross
... Data from to the manuscript "TRIM2, a novel member of the antiviral family, limits new world arenavirus entry"
Contributors: Petter Ström, Per Petersson, Anna Widdowson, Gennady Sergienko, Elżbieta Fortuna-Zaleśna, Marek Rubel
... ToF-ERDA data with partial GIC energy signals from QMB covers 1,2,3,5 (ILW-1-2). Data provided as list-files (.lst) and histogram files (.mpa) from FAST MPA-3 data acquisition system. ADC 1: Energy signal anode 1. ADC 2: Energy signal anodes 2-4. ADC 3: ToF signal.
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Synapse-selective control of cortical maturation and plasticity by Parvalbumin-autonomous action of SynCAM 1
Contributors: Adema Ribic, Michael Crair, Thomas Biederer
... Original images used for data presentation
Raw, not cropped supporting Western blot files for: Mavrommati, I., ... Pagano, M., D'Angiolella, V.: β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. Cell Rep. (2018)
Contributors: Michele Pagano
... Raw, not cropped supporting Western blot files for: Mavrommati I, Faedda R, Galasso G, Li J, Burdova K, Fischer R, Kessler BM, Carrero ZI, Guardavaccaro D, Pagano M, D'Angiolella V. β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. Cell Rep. 2018 Sep 25;24(13):3404-3412. doi: 10.1016/j.celrep.2018.08.076. PMID: 30257202 PMCID: PMC6172692 DOI: 10.1016/j.celrep.2018.08.076
Contributors: Philipp Keller
... Guide's software and data repository- compact version
Contributors: Philipp Keller
... Guide's software and data repository- full version
Contributors: Saroj Chakraborty
... Salt-responsive Metabolite, beta-hydroxybutyrate, Attenuates Hypertension Chakraborty, S1, Galla, S1, Cheng X1, Yeo, J1, Mell, B1, Singh V1, Yeoh BS1, Saha P1, Mathew, AV2, Vijay-Kumar, M1, Joe B*1. 1Program in Physiological Genomics, Microbiome Consortium, Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA. 2 Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA. *Corresponding Author: Bina Joe, email@example.com Summary Dietary salt reduction and exercise are lifestyle modifications prescribed for salt-sensitive hypertensives. While exercise is known to have prominent metabolic effects, such effects of lower dietary salt are just emerging. Studies indicate that salt has adverse effect on metabolic syndrome, of which, hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt-sensitive model of hypertension. Untargeted metabolomic profiling of rats with differential salt (NaCl) diets revealed that a high salt-induced increase in blood pressure was associated with lower circulating levels of the ketone body, beta-hydroxybutyrate (βOHB). Specific rescue of the βOHB levels by nutritional supplementation of its precursor, 1,3-butanediol attenuated hypertension and protected kidney disease despite the high salt intake. This beneficial effect of βOHB was observed independent of the gut-microbiotal effects of salt or the Th17-mediated renal effects. Instead, the mechanism for the observed renoprotective effect of βOHB on salt-sensitive hypertension was the βOHB-mediated inhibition of the pro-inflammatory cascade by the Nlrp3 inflammasome. In summary, the juxtaposed effects of dietary salt and exercise on salt-sensitive hypertension, which decrease and increase βOHB respectively, indicates that nutritional supplementation of a precursor of βOHB could be considered to provide a similar benefit to salt-sensitive hypertension as exercise.
Contributors: Agnieszka Tudek
... A nuclear export block triggers the decay of newly synthesized polyadenylated RNA Agnieszka Tudek1, Manfred Schmid1, Marius Makaras1, J. David Barrass2, Jean D. Beggs2, Torben Heick Jensen1* 1Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, building 1130, 8000 Aarhus C, Denmark, 2Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK *corresponding author and lead contact: firstname.lastname@example.org Keywords: nuclear export of pA+ RNA, nuclear degradation of pA+ RNA, Mex67p, Nab2p, transcription. ABSTRACT Genomes are promiscuously transcribed necessitating mechanisms that facilitate the sorting of RNA for function or destruction. The polyA (pA) tail is one such distinguishing feature, which in the Saccharomyces cerevisiae nucleus is bound by the Nab2p protein, yielding transcript protection. As Nab2p also contacts the main nuclear export factor Mex67p, we asked whether transport kinetics contributes to RNA sorting. Indeed, 3’end sequencing of newly transcribed pA+ RNAs demonstrates that nuclear depletion of Mex67p elicits their instant and global decay. A similar phenotype is evident upon inactivation of other export factors and proportional to the amount of nuclear pA+ RNA. As RNA expression is partially rescued by Nab2p over-expression, we propose that an export-block out-titrates Nab2p onto nuclear retained pA+ RNA, reducing the pool of Nab2p available to protect new transcripts. More generally, we suggest that nuclear RNA decay, negotiated by Nab2p availability, aids in balancing cellular transcript supply with demand.