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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Acero, F., et al.
(författare)
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Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
- 2017
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 840:2
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Tidskriftsartikel (refereegranskat)abstract
- We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
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- Meani, F, et al.
(författare)
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Investigation of the Ovarian and Prostate Cancer Peptidome for Candidate Early Detection Markers Using a Novel Nanoparticle Biomarker Capture Technology
- 2010
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Ingår i: AAPS Journal. - : Springer Science and Business Media LLC. - 1550-7416. ; 2:4, s. 504-518
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Tidskriftsartikel (refereegranskat)abstract
- Current efforts to identify protein biomarkers of disease use mainly mass spectrometry (MS) to analyze tissue and blood specimens. The low-molecular-weight "peptidome" is an attractive information archive because of the facile nature by which the low-molecular-weight information freely crosses the endothelial cell barrier of the vasculature, which provides opportunity to measure disease microenvironment-associated protein analytes secreted or shed into the extracellular interstitium and from there into the circulation. However, identifying useful protein biomarkers (peptidomic or not) which could be useful to detect early detection/monitoring of disease, toxicity, doping, or drug abuse has been severely hampered because even the most sophisticated, high-resolution MS technologies have lower sensitivities than those of the immunoassays technologies now routinely used in clinical practice. Identification of novel low abundance biomarkers that are indicative of early-stage events that likely exist in the sub-nanogram per milliliter concentration range of known markers, such as prostate-specific antigen, cannot be readily detected by current MS technologies. We have developed a new nanoparticle technology that can, in one step, capture, concentrate, and separate the peptidome from high-abundance blood proteins. Herein, we describe an initial pilot study whereby the peptidome content of ovarian and prostate cancer patients is investigated with this method. Differentially abundant candidate peptidome biomarkers that appear to be specific for early-stage ovarian and prostate cancer have been identified and reveal the potential utility for this new methodology
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- Zhong, Lei, et al.
(författare)
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The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1 alpha
- 2010
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:2, s. 280-293
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Tidskriftsartikel (refereegranskat)abstract
- SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1 alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1 alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity.
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- Pellegrini, C, et al.
(författare)
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A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration
- 2021
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Ingår i: Frontiers in aging neuroscience. - : Frontiers Media SA. - 1663-4365. ; 13, s. 639428-
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Alzheimer's disease (AD) is characterized by specific alterations of brain DNA methylation (DNAm) patterns. Age and sex, two major risk factors for AD, are also known to largely affect the epigenetic profiles in brain, but their contribution to AD-associated DNAm changes has been poorly investigated. In this study we considered publicly available DNAm datasets of four brain regions (temporal, frontal, entorhinal cortex, and cerebellum) from healthy adult subjects and AD patients, and performed a meta-analysis to identify sex-, age-, and AD-associated epigenetic profiles. In one of these datasets it was also possible to distinguish 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiles. We showed that DNAm differences between males and females tend to be shared between the four brain regions, while aging differently affects cortical regions compared to cerebellum. We found that the proportion of sex-dependent probes whose methylation is modified also during aging is higher than expected, but that differences between males and females tend to be maintained, with only a few probes showing age-by-sex interaction. We did not find significant overlaps between AD- and sex-associated probes, nor disease-by-sex interaction effects. On the contrary, we found that AD-related epigenetic modifications are significantly enriched in probes whose DNAm varies with age and that there is a high concordance between the direction of changes (hyper or hypo-methylation) in aging and AD, supporting accelerated epigenetic aging in the disease. In summary, our results suggest that age-associated DNAm patterns concur to the epigenetic deregulation observed in AD, providing new insights on how advanced age enables neurodegeneration.
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