Breaks in Coordination: DNA Repair in Inherited Ataxia

Genetic defects in DNA repair are increasingly recognized as being able to cause degenerative ataxia syndromes. It remains a mystery, however, why disruption of a process fundamental to proliferating cells can be selectively toxic to postmitotic neurons. Recent studies now reveal that an ataxia gene, tyrosyl phosphodiesterase 1 (TDP1), repairs single-stranded DNA breaks in nondividing cells. Here we review the implications of this and other findings for a growing list of hereditary ataxias

C9orf72-Associated FTD/ALS: When Less Is More

Hexanucleotide repeat expansions in C9ORF72 cause neurodegeneration in FTD and ALS by unknown mechanisms. A new report, by Donnelly et al. (2013), finds that these repeats trigger a pathogenic gain-of-function cascade that can be corrected by suppressing expression of the repeat transcript, paving the way for therapeutic strategies aimed at eliminating the toxic RNA

RNA-mediated neurodegeneration in repeat expansion disorders

Most neurodegenerative disorders are thought to result primarily from the accumulation of misfolded proteins, which interfere with protein homeostasis in neurons. For a subset of diseases, however, noncoding regions of RNAs assume a primary toxic gain-of-function, leading to degeneration in many tissues, including the nervous system. Here we review a series of proposed mechanisms by which noncoding repeat expansions give rise to nervous system degeneration and dysfunction. These mechanisms include transcriptional alterations and the generation of antisense transcripts, sequestration of mRNA-associated protein complexes that lead to aberrant mRNA splicing and processing, and alterations in cellular processes, including activation of abnormal signaling cascades and failure of protein quality control pathways. We place these potential mechanisms in the context of known RNA-mediated disorders, including the myotonic dystrophies and fragile X tremor ataxia syndrome, and discuss recent results suggesting that mRNA toxicity may also play a role in some presumably protein-mediated neurodegenerative disorders. Lastly, we comment on recent progress in therapeutic development for these RNA-dominant diseases. ANN NEUROL 2010;67:291–300Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69199/1/21948_ftp.pd

Treatment for Anogenital Molluscum Contagiosum

There is no evidence from comparative trials to suggest a single best treatment method for anogenital molluscum contagiosum. Randomized controlled trials suggest self-administered topical imiquimod or podophyllotoxin cream is effective for resolving lesions. (Strength of Recommendation: B, based on inconsistent or limited quality patient-oriented evidence). There are no comparative trials of other commonly used treatments, such as carbon dioxide laser, cryotherapy, or curettage

P4‐154: The Protein Quality Control Protein, Ubiquilin‐2, Regulates Tau Accumulation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152960/1/alzjjalz2019063816.pd

Limits of ultra-high-precision optical astrometry: Stellar surface structures

We investigate the astrometric effects of stellar surface structures as a practical limitation to ultra-high-precision astrometry, e.g. in the context of exoplanet searches, and to quantify the expected effects in different regions of the HR-diagram. Stellar surface structures are likely to produce fluctuations in the integrated flux and radial velocity of the star, as well as a variation of the observed photocentre, i.e. astrometric jitter, and closure phase. We use theoretical considerations supported by Monte Carlo simulations to derive statistical relations between the corresponding astrometric, photometric, and radial-velocity effects. For most stellar types the astrometric jitter due to stellar surface structures is expected to be of order 10 micro-AU or greater. This is more than the astrometric displacement typically caused by an Earth-size exoplanet in the habitable zone, which is about 1-4 micro-AU for long-lived main-sequence stars. Only for stars with extremely low photometric variability (<0.5 mmag) and low magnetic activity, comparable to that of the Sun, will the astrometric jitter be of order 1 micro-AU, suffcient to allow the astrometric detection of an Earth-sized planet in the habitable zone. While stellar surface structure may thus seriously impair the astrometric detection of small exoplanets, it has in general negligible impact on the detection of large (Jupiter-size) planets and on the determination of stellar parallax and proper motion. From the starspot model we also conclude that the commonly used spot filling factor is not the most relevant parameter for quantifying the spottiness in terms of the resulting astrometric, photometric and radial-velocity variations.Comment: 12 pages, 4 figures, submitted to A&

The CRIRES Search for Planets Around the Lowest-Mass Stars. I. High-Precision Near-Infrared Radial Velocities with an Ammonia Gas Cell

Radial velocities measured from near-infrared spectra are a potentially powerful tool to search for planets around cool stars and sub-stellar objects. However, no technique currently exists that yields near-infrared radial velocity precision comparable to that routinely obtained in the visible. We describe a method for measuring high-precision relative radial velocities of these stars from K-band spectra. The method makes use of a glass cell filled with ammonia gas to calibrate the spectrograph response similar to the "iodine cell" technique that has been used very successfully in the visible. Stellar spectra are obtained through the ammonia cell and modeled as the product of a Doppler-shifted template spectrum of the object and a spectrum of the cell, convolved with a variable instrumental profile model. A complicating factor is that a significant number of telluric absorption lines are present in the spectral regions containing useful stellar and ammonia lines. The telluric lines are modeled simultaneously as well using spectrum synthesis with a time-resolved model of the atmosphere over the observatory. The free parameters in the complete model are the wavelength scale of the spectrum, the instrumental profile, adjustments to the water and methane abundances in the atmospheric model, telluric spectrum Doppler shift, and stellar Doppler shift. Tests of the method based on the analysis of hundreds of spectra obtained for late M dwarfs over six months demonstrate that precisions of ~5 m/s are obtainable over long timescales, and precisions of better than 3 m/s can be obtained over timescales up to a week. The obtained precision is comparable to the predicted photon-limited errors, but primarily limited over long timescales by the imperfect modeling of the telluric lines.Comment: Accepted for publication in Ap

Rotation periods of exoplanet host stars

The stellar rotation periods of ten exoplanet host stars have been determined using newly analysed Ca II H & K flux records from Mount Wilson Observatory and Stromgren b, y photometric measurements from Tennessee State University's automatic photometric telescopes (APTs) at Fairborn Observatory. Five of the rotation periods have not previously been reported, with that of HD 130322 very strongly detected at Prot = 26.1 \pm 3.5 d. The rotation periods of five other stars have been updated using new data. We use the rotation periods to derive the line-of-sight inclinations of the stellar rotation axes, which may be used to probe theories of planet formation and evolution when combined with the planetary orbital inclination found from other methods. Finally, we estimate the masses of fourteen exoplanets under the assumption that the stellar rotation axis is aligned with the orbital axis. We calculate the mass of HD 92788 b (28 MJ) to be within the low-mass brown dwarf regime and suggest that this object warrants further investigation to confirm its true nature.Comment: Accepted for publication in MNRAS. 15 pages, 11 figure

Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin‐3

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102210/1/emboj2008289-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102210/2/emboj2008289.pd