Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Discovery of Small-Scale Spiral Structures in the Disk of SAO 206462 (HD 135344B): Implications for the Physical State of the Disk from Spiral Density Wave Theory

We present high-resolution, H-band, imaging observations, collected with Subaru/HiCIAO, of the scattered light from the transitional disk around SAO 206462 (HD 135344B). Although previous sub-mm imagery suggested the existence of the dust-depleted cavity at r~46AU, our observations reveal the presence of scattered light components as close as 0.2" (~28AU) from the star. Moreover, we have discovered two small-scale spiral structures lying within 0.5" (~70AU). We present models for the spiral structures using the spiral density wave theory, and derive a disk aspect ratio of h~0.1, which is consistent with previous sub-mm observations. This model can potentially give estimates of the temperature and rotation profiles of the disk based on dynamical processes, independently from sub-mm observations. It also predicts the evolution of the spiral structures, which can be observable on timescales of 10-20 years, providing conclusive tests of the model. While we cannot uniquely identify the origin of these spirals, planets embedded in the disk may be capable of exciting the observed morphology. Assuming that this is the case, we can make predictions on the locations and, possibly, the masses of the unseen planets. Such planets may be detected by future multi-wavelengths observations.Comment: 8 pages, 5 figures, ApJL in press, typo correcte

Longitudinal accumulation of cerebral microhemorrhages in dominantly inherited Alzheimer disease

OBJECTIVE: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we longitudinally evaluated families with dominantly inherited Alzheimer disease (DIAD). METHODS: Mutation carriers (n = 310) and noncarriers (n = 201) underwent neuroimaging, including gradient echo MRI sequences to detect CMHs, and neuropsychological and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical markers of disease. RESULTS: Three percent of noncarriers and 8% of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMHs. CONCLUSION: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug-related CMHs

High-Resolution Near-Infrared Polarimetry of a Circumstellar Disk around UX Tau A

We present H-band polarimetric imagery of UX Tau A taken with HiCIAO/AO188 on the Subaru Telescope. UX Tau A has been classified as a pre-transitional disk object, with a gap structure separating its inner and outer disks. Our imagery taken with the 0.15 (21 AU) radius coronagraphic mask has revealed a strongly polarized circumstellar disk surrounding UX Tau A which extends to 120 AU, at a spatial resolution of 0.1 (14 AU). It is inclined by 46 \pm 2 degree as the west side is nearest. Although SED modeling and sub-millimeter imagery suggested the presence of a gap in the disk, with the inner edge of the outer disk estimated to be located at 25 - 30 AU, we detect no evidence of a gap at the limit of our inner working angle (23 AU) at the near-infrared wavelength. We attribute the observed strong polarization (up to 66 %) to light scattering by dust grains in the disk. However, neither polarization models of the circumstellar disk based on Rayleigh scattering nor Mie scattering approximations were consistent with the observed azimuthal profile of the polarization degrees of the disk. Instead, a geometric optics model of the disk with nonspherical grains with the radii of 30 micron meter is consistent with the observed profile. We suggest that the dust grains have experienced frequent collisional coagulations and have grown in the circumstellar disk of UX Tau A.Comment: 20 pages, 8 figures, and 1 table. accepted to PAS

Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

Minimotif Miner 3.0: database expansion and significantly improved reduction of false-positive predictions from consensus sequences

Minimotif Miner (MnM available at http://minimotifminer.org or http://mnm.engr.uconn.edu) is an online database for identifying new minimotifs in protein queries. Minimotifs are short contiguous peptide sequences that have a known function in at least one protein. Here we report the third release of the MnM database which has now grown 60-fold to approximately 300 000 minimotifs. Since short minimotifs are by their nature not very complex we also summarize a new set of false-positive filters and linear regression scoring that vastly enhance minimotif prediction accuracy on a test data set. This online database can be used to predict new functions in proteins and causes of disease

Selenocysteine Insertion Sequence Binding Protein 2L Is Implicated as a Novel Post-Transcriptional Regulator of Selenoprotein Expression

The amino acid selenocysteine (Sec) is encoded by UGA codons. Recoding of UGA from stop to Sec requires a Sec insertion sequence (SECIS) element in the 3′ UTR of selenoprotein mRNAs. SECIS binding protein 2 (SBP2) binds the SECIS element and is essential for Sec incorporation into the nascent peptide. SBP2-like (SBP2L) is a paralogue of SBP2 in vertebrates and is the only SECIS binding protein in some invertebrates where it likely directs Sec incorporation. However, vertebrate SBP2L does not promote Sec incorporation in in vitro assays. Here we present a comparative analysis of SBP2 and SBP2L SECIS binding properties and demonstrate that its inability to promote Sec incorporation is not due to lower SECIS affinity but likely due to lack of a SECIS dependent domain association that is found in SBP2. Interestingly, however, we find that an invertebrate version of SBP2L is fully competent for Sec incorporation in vitro. Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression