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  • 1
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    Mitochondrial quality control pathways as determinants of metabolic health (2015)
    Wiley
    In: BioEssays
    Details
    Publication Date: 2015-05-27
    Description: Mitochondrial function is key for maintaining cellular health, while mitochondrial failure is associated with various pathologies, including inherited metabolic disorders and age-related diseases. In order to maintain mitochondrial quality, several pathways of mitochondrial quality control have evolved. These systems monitor mitochondrial integrity through antioxidants, DNA repair systems, and chaperones and proteases involved in the mitochondrial unfolded protein response. Additional regulation of mitochondrial function involves dynamic exchange of components through mitochondrial fusion and fission. Sustained stress induces a selective autophagy – termed mitophagy – and ultimately leads to apoptosis. Together, these systems form a network that acts on the molecular, organellar, and cellular level. In this review, we highlight how these systems are regulated in an integrated context- and time-dependent network of mitochondrial quality control that is implicated in healthy aging. Mitochondrial stress is an important hallmark of metabolic diseases and aging. Various mitochondrial stress response pathways are in place to counter this imposed stress. In this review, we discuss the existing mitochondrial quality control pathways, and focus on the recent insight that these pathways are highly context- and time-dependent.
    Print ISSN: 0265-9247
    Electronic ISSN: 1521-1878
    Topics: Biology , Medicine
    Published by Wiley
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  • 2
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    Kinetic energy-conserving hyperdiffusion can improve low-resolution atmospheric models (2015)
    Wiley
    Details
    Publication Date: 2015-07-09
    Description: Motivated by findings that energetically-consistent subgrid dissipation schemes can improve eddy-permitting ocean simulations, this work investigates the impact of the subgrid dissipation scheme on low-resolution atmospheric dynamical cores. A kinetic energy-conserving dissipation scheme is implemented in the model adding a negative viscosity term that injects back into the eddy field the kinetic energy dissipated by horizontal hyperdiffusion. The kinetic energy-conserving scheme enhances numerical convergence when horizontal resolution is changed with fixed vertical resolution and gives superior low-resolution results. Improvements are most obvious for eddy kinetic energy but also found in other fields, particularly with strong or little scale-selective horizontal hyperdiffusion. One advantage of the kinetic energy-conserving scheme is that it reduces the sensitivity of the model to changes in the subgrid dissipation rate, providing more robust results. This article is protected by copyright. All rights reserved.
    Electronic ISSN: 1942-2466
    Topics: Geography , Geosciences
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
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    36 new, high-probability, damped Ly{alpha} absorbers at redshift 0.42 〈 z 〈 0.70 (2015)
    Oxford University Press
    Details
    Publication Date: 2015-03-26
    Description: Quasar damped Lyα (DLA) absorption-line systems with redshifts z  〈 1.65 are used to trace neutral gas over approximately 70 per cent of the most recent history of the Universe. However, such systems fall in the UV and are rarely found in blind UV spectroscopic surveys. Therefore, it has been difficult to compile a moderate-sized sample of UV DLAs in any narrow cosmic time interval. However, DLAs are easy to identify in low-resolution spectra because they have large absorption rest equivalent widths. We have performed an efficient strong-Mg  ii -selected survey for UV DLAs at redshifts z  = [0.42, 0.70] using Hubble Space Telescope 's low-resolution ACS-HRC-PR200L prism. This redshift interval covers ~1.8 Gyr in cosmic time, i.e. t   [7.2, 9.0] Gyr after the big bang. A total of 96 strong Mg  ii absorption-line systems identified in Sloan Digital Sky Survey spectra were successfully observed with the prism at the predicted UV wavelengths of Lyα absorption. We found that 35 of the 96 systems had a significant probability of being DLAs. One additional observed system could be a very high $N_{\rm H\,\small {I}}$ DLA ( $N_{\rm H\,\small {I}} \sim 2\times 10^{22}$ atoms cm –2 or possibly higher), but since very high $N_{\rm H\,\small {I}}$ systems are extremely rare, it would be unusual for this system to be a DLA given the size of our sample. Here we present information on our prism sample, including our best estimates of $N_{\rm H\,\small {I}}$ and errors for the 36 systems fitted with DLA profiles. This list is valuable for future follow-up studies of low-redshift DLAs in a small redshift interval, although such work would clearly benefit from improved UV spectroscopy to more accurately determine their neutral hydrogen column densities.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 4
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    Multiplexed, Scheduled, High-Resolution Parallel Reaction Monitoring on a Full Scan QqTOF Instrument with Integrated Data-Dependent and Targeted Mass Spectrometric Workflows (2015)
    American Chemical Society (ACS)
    Details
    Publication Date: 2015-10-02
    Description: Analytical Chemistry DOI: 10.1021/acs.analchem.5b02983
    Print ISSN: 0003-2700
    Electronic ISSN: 1520-6882
    Topics: Chemistry and Pharmacology
    Published by American Chemical Society (ACS)
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  • 5
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    Surface temperature dependence of tropical cyclone-permitting simulations in a spherical model with uniform thermal forcing (2016)
    Wiley
    Details
    Publication Date: 2016-02-24
    Description: Tropical cyclone (TC)-permitting general circulation model simulations are performed with spherical geometry and uniform thermal forcing, including uniform sea surface temperature (SST) and insolation. The dependence of the TC number and TC intensity on SST is examined in a series of simulations with varied SST. The results are compared to corresponding simulations with doubly periodic f -plane geometry, rotating radiative convective equilibrium. The turbulent equilibria in simulations with spherical geometry have an inhomogenous distribution of TCs with the density of TCs increasing from low-to-high latitudes. The preferred region of TC genesis is the subtropics, but genesis shifts poleward and becomes less frequent with increasing SST. Both rotating radiative convective equilibrium and spherical geometry simulations have decreasing TC number and increasing TC intensity as SST is increased.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    The control of surface friction on the scales of baroclinic eddies in a homogeneous quasigeostrophic two-layer model (2019)
    American Meteorological Society (AMS)
    Details
    Publication Date: 2019
    Description: Journal of the Atmospheric Sciences, Ahead of Print. 〈br/〉
    Print ISSN: 0095-9634
    Electronic ISSN: 1520-0469
    Topics: Geography , Geosciences , Physics
    Published by American Meteorological Society (AMS)
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  • 7
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    Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes (2010)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2010-04-03
    Description: Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the approximately 21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108885/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108885/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Neumann, Beate -- Walter, Thomas -- Heriche, Jean-Karim -- Bulkescher, Jutta -- Erfle, Holger -- Conrad, Christian -- Rogers, Phill -- Poser, Ina -- Held, Michael -- Liebel, Urban -- Cetin, Cihan -- Sieckmann, Frank -- Pau, Gregoire -- Kabbe, Rolf -- Wunsche, Annelie -- Satagopam, Venkata -- Schmitz, Michael H A -- Chapuis, Catherine -- Gerlich, Daniel W -- Schneider, Reinhard -- Eils, Roland -- Huber, Wolfgang -- Peters, Jan-Michael -- Hyman, Anthony A -- Durbin, Richard -- Pepperkok, Rainer -- Ellenberg, Jan -- 077192/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Apr 1;464(7289):721-7. doi: 10.1038/nature08869.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20360735" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division/*genetics ; Cell Movement/genetics ; Cell Survival/genetics ; Color ; Gene Knockdown Techniques ; Genes/genetics ; Genome, Human/*genetics ; HeLa Cells ; Humans ; Kinetics ; Mice ; Microscopy, Fluorescence/*methods ; Mitosis/genetics ; *Phenotype ; RNA Interference ; Reproducibility of Results ; Spindle Apparatus/genetics/metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 8
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    Modeled impact of anthropogenic warming on the frequency of intense Atlantic hurricanes (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-01-23
    Description: Several recent models suggest that the frequency of Atlantic tropical cyclones could decrease as the climate warms. However, these models are unable to reproduce storms of category 3 or higher intensity. We explored the influence of future global warming on Atlantic hurricanes with a downscaling strategy by using an operational hurricane-prediction model that produces a realistic distribution of intense hurricane activity for present-day conditions. The model projects nearly a doubling of the frequency of category 4 and 5 storms by the end of the 21st century, despite a decrease in the overall frequency of tropical cyclones, when the downscaling is based on the ensemble mean of 18 global climate-change projections. The largest increase is projected to occur in the Western Atlantic, north of 20 degrees N.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bender, Morris A -- Knutson, Thomas R -- Tuleya, Robert E -- Sirutis, Joseph J -- Vecchi, Gabriel A -- Garner, Stephen T -- Held, Isaac M -- New York, N.Y. -- Science. 2010 Jan 22;327(5964):454-8. doi: 10.1126/science.1180568.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Oceanic and Atmospheric Administration/Geophysical Fluid Dynamics Laboratory, 201 Forrestal Road, Princeton, NJ 08540, USA. Morris.Bender@noaa.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20093471" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 9
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    N-acylethanolamine signalling mediates the effect of diet on lifespan in Caenorhabditis elegans (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-05-13
    Description: Dietary restriction is a robust means of extending adult lifespan and postponing age-related disease in many species, including yeast, nematode worms, flies and rodents. Studies of the genetic requirements for lifespan extension by dietary restriction in the nematode Caenorhabditis elegans have implicated a number of key molecules in this process, including the nutrient-sensing target of rapamycin (TOR) pathway and the Foxa transcription factor PHA-4 (ref. 7). However, little is known about the metabolic signals that coordinate the organismal response to dietary restriction and maintain homeostasis when nutrients are limited. The endocannabinoid system is an excellent candidate for such a role given its involvement in regulating nutrient intake and energy balance. Despite this, a direct role for endocannabinoid signalling in dietary restriction or lifespan determination has yet to be demonstrated, in part due to the apparent absence of endocannabinoid signalling pathways in model organisms that are amenable to lifespan analysis. N-acylethanolamines (NAEs) are lipid-derived signalling molecules, which include the mammalian endocannabinoid arachidonoyl ethanolamide. Here we identify NAEs in C. elegans, show that NAE abundance is reduced under dietary restriction and that NAE deficiency is sufficient to extend lifespan through a dietary restriction mechanism requiring PHA-4. Conversely, dietary supplementation with the nematode NAE eicosapentaenoyl ethanolamide not only inhibits dietary-restriction-induced lifespan extension in wild-type worms, but also suppresses lifespan extension in a TOR pathway mutant. This demonstrates a role for NAE signalling in ageing and indicates that NAEs represent a signal that coordinates nutrient status with metabolic changes that ultimately determine lifespan.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093655/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093655/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lucanic, Mark -- Held, Jason M -- Vantipalli, Maithili C -- Klang, Ida M -- Graham, Jill B -- Gibson, Bradford W -- Lithgow, Gordon J -- Gill, Matthew S -- PL1-AG032118/AG/NIA NIH HHS/ -- R01 AG029631/AG/NIA NIH HHS/ -- R01 AG036992/AG/NIA NIH HHS/ -- R01AG029631/AG/NIA NIH HHS/ -- R21 AG030192/AG/NIA NIH HHS/ -- T32 AG000266/AG/NIA NIH HHS/ -- T32 AG000266-13/AG/NIA NIH HHS/ -- T32AG000266/AG/NIA NIH HHS/ -- UL1 DE019608/DE/NIDCR NIH HHS/ -- UL1 RR024917/RR/NCRR NIH HHS/ -- England -- Nature. 2011 May 12;473(7346):226-9. doi: 10.1038/nature10007.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21562563" target="_blank"〉PubMed〈/a〉
    Keywords: Amides/pharmacology ; Amidohydrolases/metabolism ; Animals ; Caenorhabditis elegans/drug effects/genetics/growth & ; development/metabolism/*physiology ; Caenorhabditis elegans Proteins/metabolism ; Caloric Restriction ; *Diet ; Ethanolamines/*metabolism ; Gene Expression Regulation, Developmental ; Longevity/drug effects/*physiology ; Mutation ; *Signal Transduction ; Trans-Activators/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Crystal structure of nucleotide-free dynamin (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-09-20
    Description: Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faelber, Katja -- Posor, York -- Gao, Song -- Held, Martin -- Roske, Yvette -- Schulze, Dennis -- Haucke, Volker -- Noe, Frank -- Daumke, Oliver -- England -- Nature. 2011 Sep 18;477(7366):556-60. doi: 10.1038/nature10369.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crystallography, Max-Delbruck-Centrum for Molecular Medicine, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. katja.faelber@mdc-berlin.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21927000" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Dynamin I/*chemistry/metabolism ; Dynamin II/genetics/metabolism ; GTP Phosphohydrolases/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; HeLa Cells ; Humans ; Hydrolysis ; Models, Molecular ; Molecular Dynamics Simulation ; *Nucleotides ; Protein Binding ; Protein Structure, Tertiary ; Signal Transduction ; Transferrin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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