134 research outputs found
Corrigendum: RNA Polymerase III, Ageing and Longevity
[This corrects the article DOI: 10.3389/fgene.2021.705122.]
Partial inhibition of RNA polymerase I promotes animal health and longevity
Health and survival in old age can be improved by changes in gene expression. RNA polymerase (Pol) I is the essential, conserved enzyme whose task is to generate the pre-ribosomal RNA (rRNA). We find that reducing the levels of Pol I activity is sufficient to extend lifespan in the fruit fly. This effect can be recapitulated by partial, adult-restricted inhibition, with both enterocytes and stem cells of the adult midgut emerging as important cell types. In stem cells, Pol I appears to act in the same longevity pathway as Pol III, implicating rRNA synthesis in these cells as the key lifespan determinant. Importantly, reduction in Pol I activity delays broad, age-related impairment and pathology, improving the function of diverse organ systems. Hence, our study shows that Pol I activity in the adult drives systemic, age-related decline in animal health and anticipates mortality
Implementation of standard testbeds for numerical relativity
We discuss results that have been obtained from the implementation of the
initial round of testbeds for numerical relativity which was proposed in the
first paper of the Apples with Apples Alliance. We present benchmark results
for various codes which provide templates for analyzing the testbeds and to
draw conclusions about various features of the codes. This allows us to sharpen
the initial test specifications, design a new test and add theoretical insight.Comment: Corrected versio
Trametinib ameliorates aging-associated gut pathology in Drosophila females by reducing Pol III activity in intestinal stem cells
Pharmacological therapies are promising interventions to slow down aging and reduce multimorbidity in the elderly. Studies in animal models are the first step toward translation of candidate molecules into human therapies, as they aim to elucidate the molecular pathways, cellular mechanisms, and tissue pathologies involved in the anti-aging effects. Trametinib, an allosteric inhibitor of MEK within the Ras/MAPK (Ras/Mitogen-Activated Protein Kinase) pathway and currently used as an anti-cancer treatment, emerged as a geroprotector candidate because it extended lifespan in the fruit fly
Drosophila melanogaster
. Here, we confirm that trametinib consistently and robustly extends female lifespan, and reduces intestinal stem cell (ISC) proliferation, tumor formation, tissue dysplasia, and barrier disruption in guts in aged flies. In contrast, pro-longevity effects of trametinib are weak and inconsistent in males, and it does not influence gut homeostasis. Inhibition of the Ras/MAPK pathway specifically in ISCs is sufficient to partially recapitulate the effects of trametinib. Moreover, in ISCs, trametinib decreases the activity of the RNA polymerase III (Pol III), a conserved enzyme synthesizing transfer RNAs and other short, non-coding RNAs, and whose inhibition also extends lifespan and reduces gut pathology. Finally, we show that the pro-longevity effect of trametinib in ISCs is partially mediated by Maf1, a repressor of Pol III, suggesting a life-limiting Ras/MAPK-Maf1-Pol III axis in these cells. The mechanism of action described in this work paves the way for further studies on the anti-aging effects of trametinib in mammals and shows its potential for clinical application in humans
Three little pieces for computer and relativity
Numerical relativity has made big strides over the last decade. A number of
problems that have plagued the field for years have now been mostly solved.
This progress has transformed numerical relativity into a powerful tool to
explore fundamental problems in physics and astrophysics, and I present here
three representative examples. These "three little pieces" reflect a personal
choice and describe work that I am particularly familiar with. However, many
more examples could be made.Comment: 42 pages, 11 figures. Plenary talk at "Relativity and Gravitation:
100 Years after Einstein in Prague", June 25 - 29, 2012, Prague, Czech
Republic. To appear in the Proceedings (Edition Open Access). Collects
results appeared in journal articles [72,73, 122-124
A Multifunctional Interlayer for Solution Processed High Performance Indium Oxide Transistors
International audienceMultiple functionality of tungsten polyoxometalate (POM) has been achieved applying it as interfacial layer for solution processed high performance In 2 O 3 thin film transistors, which results in overall improvement of device performance. This approach not only reduces off-current of the device by more than two orders of magnitude, but also leads to a threshold voltage reduction, as well as significantly enhances the mobility through facilitated charge injection from the electrode to the active layer. Such a mechanism has been elucidated through morphological and spectroscopic studies
From Geometry to Numerics: interdisciplinary aspects in mathematical and numerical relativity
This article reviews some aspects in the current relationship between
mathematical and numerical General Relativity. Focus is placed on the
description of isolated systems, with a particular emphasis on recent
developments in the study of black holes. Ideas concerning asymptotic flatness,
the initial value problem, the constraint equations, evolution formalisms,
geometric inequalities and quasi-local black hole horizons are discussed on the
light of the interaction between numerical and mathematical relativists.Comment: Topical review commissioned by Classical and Quantum Gravity.
Discussion inspired by the workshop "From Geometry to Numerics" (Paris, 20-24
November, 2006), part of the "General Relativity Trimester" at the Institut
Henri Poincare (Fall 2006). Comments and references added. Typos corrected.
Submitted to Classical and Quantum Gravit
Supermassive Black Hole Binaries: The Search Continues
Gravitationally bound supermassive black hole binaries (SBHBs) are thought to
be a natural product of galactic mergers and growth of the large scale
structure in the universe. They however remain observationally elusive, thus
raising a question about characteristic observational signatures associated
with these systems. In this conference proceeding I discuss current theoretical
understanding and latest advances and prospects in observational searches for
SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat
Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed.
C.Sopuerta (Berlin: Springer-Verlag
Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration
The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a joint effort between members of the numerical relativity, analytical relativity and gravitational-wave data analysis communities. The goal of the NRAR collaboration is to produce numerical-relativity simulations of compact binaries and use them to develop accurate analytical templates for the LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and extracting astrophysical information from them. We describe the results of the first stage of the NRAR project, which focused on producing an initial set of numerical waveforms from binary black holes with moderate mass ratios and spins, as well as one non-spinning binary configuration which has a mass ratio of 10. All of the numerical waveforms are analysed in a uniform and consistent manner, with numerical errors evaluated using an analysis code created by members of the NRAR collaboration. We compare previously-calibrated, non-precessing analytical waveforms, notably the effective-one-body (EOB) and phenomenological template families, to the newly-produced numerical waveforms. We find that when the binary's total mass is ~100-200 solar masses, current EOB and phenomenological models of spinning, non-precessing binary waveforms have overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary numerical waveforms with mass ratios <= 4, when maximizing over binary parameters. This implies that the loss of event rate due to modelling error is below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to five non-spinning waveforms with mass ratio smaller than 6 have overlaps above 99.7% with the numerical waveform with a mass ratio of 10, without even maximizing on the binary parameters
DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6
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