Publications by authors named "Matthew J Grant"

4 Publications

  • Page 1 of 1

Castration delays epigenetic aging and feminizes DNA methylation at androgen-regulated loci.

Elife 2021 07 6;10. Epub 2021 Jul 6.

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.

In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data. In this study, we developed the first epigenetic clock for domesticated sheep (), which can predict chronological age with a median absolute error of 5.1 months. We have discovered that castrated male sheep have a decelerated aging rate compared to intact males, mediated at least in part by the removal of androgens. Furthermore, we identified several androgen-sensitive CpG dinucleotides that become progressively hypomethylated with age in intact males, but remain stable in castrated males and females. Comparable sex-specific methylation differences in also exist in bat skin and a range of mouse tissues that have high androgen receptor expression, indicating that it may drive androgen-dependent hypomethylation in divergent mammalian species. In characterizing these sites, we identify biologically plausible mechanisms explaining how androgens drive male-accelerated aging.
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http://dx.doi.org/10.7554/eLife.64932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260231PMC
July 2021

Rotation sensitivity and shot-noise-limited detection in an exceptional-point coupled-ring gyroscope.

Opt Lett 2021 Jun;46(12):2936-2939

A theoretical study is performed of the sensitivity and quantum-noise limit of a passive coupled-ring optical gyroscope operated at and detuned from its exceptional point (EP) and interrogated with a practical conventional readout system. When tuned to its EP, the Sagnac frequency splitting is proportional to the square root of the applied rotation rate, but the signal generated by the sensor is shown to be proportional to the applied rotation rate. The sensitivity is never larger, and the minimum detectable rotation rate in the quantum-noise limit never lower, than that of a standard single-ring gyro of the same radius and loss, even when the coupled-ring gyro is tuned exactly to its EP. As pointed out elsewhere for other EP sensors, in this particular passive sensor at least, there is no sensitivity or resolution benefit in operating at an EP.
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http://dx.doi.org/10.1364/OL.423700DOI Listing
June 2021

Enhanced rotation sensing and exceptional points in a parity-time-symmetric coupled-ring gyroscope.

Opt Lett 2020 Dec;45(23):6538-6541

Enhancement in rotation sensitivity is achieved in a parity-time-symmetric gyroscope consisting of a ring with gain coupled to a lossy ring, operated below laser threshold and in the vicinity of its exceptional point (EP). An external laser and a conventional readout system are used to measure the large rotation-induced shifts in resonance frequency known to occur in this device. A complete model of the rotation sensitivity is derived that accounts for gain saturation caused by the large circulating power. Compared to a single-ring gyro, the sensitivity is enhanced by a factor of ∼300 when the inter-ring coupling is tuned to its EP value , and ∼2400 when it is decreased from , even though the Sagnac frequency shift is then much smaller. ∼40 of this 2400-fold enhancement is assigned to a new sensing mechanism where rotation alters the gain saturation. These results show that this compact gyro has a far greater sensitivity than a conventional ring gyro, and that this improvement arises mostly from the gain compensating the loss, as opposed to the enhanced Sagnac frequency shift from the EP. This gyro is also shown to be much more stable against gain fluctuations than a single-ring gyro with gain.
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http://dx.doi.org/10.1364/OL.399985DOI Listing
December 2020

DNA methylation study of Huntington's disease and motor progression in patients and in animal models.

Nat Commun 2020 09 10;11(1):4529. Epub 2020 Sep 10.

Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.

Although Huntington's disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10) associated with 33 CpG sites, including the HTT gene (p = 6.5 × 10). These Htt/HTT associations were replicated in the Q175 Htt knock-in mouse model (p = 6.0 × 10) and in the transgenic sheep model (p = 2.4 × 10). We define a measure of HD motor score progression among manifest HD cases based on multiple clinical assessments. EWAS of motor progression in manifest HD cases exhibits significant (p < 10) associations with methylation levels at three loci: near PEX14 (p = 9.3 × 10), GRIK4 (p = 3.0 × 10), and COX4I2 (p = 6.5 × 10). We conclude that HD is accompanied by profound changes of DNA methylation levels in three mammalian species.
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http://dx.doi.org/10.1038/s41467-020-18255-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484780PMC
September 2020
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