Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo

RNA has a dual role as an informational molecule and a direct effector of biological tasks. The latter function is enabled by RNA’s ability to adopt complex secondary and tertiary folds and thus has motivated extensive computational and experimental efforts for determining RNA structures. Existing approaches for evaluating RNA structure have been largely limited to in vitro systems, yet the thermodynamic forces which drive RNA folding in vitro may not be sufficient to predict stable RNA structures in vivo. Indeed, the presence of RNA-binding proteins and ATP-dependent helicases can influence which structures are present inside cells. Here we present an approach for globally monitoring RNA structure in native conditions in vivo with single-nucleotide precision. This method is based on in vivo modification with dimethyl sulphate (DMS), which reacts with unpaired adenine and cytosine residues, followed by deep sequencing to monitor modifications. Our data from yeast and mammalian cells are in excellent agreement with known messenger RNA structures and with the high-resolution crystal structure of the Saccharomyces cerevisiae ribosome. Comparison between in vivo and in vitro data reveals that in rapidly dividing cells there are vastly fewer structured mRNA regions in vivo than in vitro. Even thermostable RNA structures are often denatured in cells, highlighting the importance of cellular processes in regulating RNA structure. Indeed, analysis of mRNA structure under ATP-depleted conditions in yeast shows that energy-dependent processes strongly contribute to the predominantly unfolded state of mRNAs inside cells. Our studies broadly enable the functional analysis of physiological RNA structures and reveal that, in contrast to the Anfinsen view of protein folding whereby the structure formed is the most thermodynamically favourable, thermodynamics have an incomplete role in determining mRNA structure in vivo

Two-step phase changes in cubic relaxor ferroelectrics

The field-driven conversion between the zero-field-cooled frozen relaxor state and a ferroelectric state of several cubic relaxors is found to occur in at least two distinct steps, after a period of creep, as a function of time. The relaxation of this state back to a relaxor state under warming in zero field also occurs via two or more sharp steps, in contrast to a one-step relaxation of the ferroelectric state formed by field-cooling. An intermediate state can be trapped by interrupting the polarization. Giant pyroelectric noise appears in some of the non-equilibrium regimes. It is suggested that two coupled types of order, one ferroelectric and the other glassy, may be required to account for these data.Comment: 27 pages with 8 figures to appear in Phys. Rev.

Keck Pencil-Beam Survey for Faint Kuiper Belt Objects

We present the results of a pencil-beam survey of the Kuiper Belt using the Keck 10-m telescope. A single 0.01 square degree field is imaged 29 times for a total integration time of 4.8 hr. Combining exposures in software allows the detection of Kuiper Belt Objects (KBOs) having visual magnitude V < 27.9. Two new KBOs are discovered. One object having V = 25.5 lies at a probable heliocentric distance d = 33 AU. The second object at V = 27.2 is located at d = 44 AU. Both KBOs have diameters of about 50 km, assuming comet-like albedos of 4%. Data from all surveys are pooled to construct the luminosity function from red magnitude R = 20 to 27. The cumulative number of objects per square degree, N (< R), is fitted to a power law of the form log_(10) N = 0.52 (R - 23.5). Differences between power laws reported in the literature are due mainly to which survey data are incorporated, and not to the method of fitting. The luminosity function is consistent with a power-law size distribution for objects having diameters s = 50 to 500 km; dn ~ s^(-q) ds, where the differential size index q = 3.6 +/- 0.1. The distribution is such that the smallest objects possess most of the surface area, but the largest bodies contain the bulk of the mass. Though our inferred size index nearly matches that derived by Dohnanyi (1969), it is unknown whether catastrophic collisions are responsible for shaping the size distribution. Implications of the absence of detections of classical KBOs beyond 50 AU are discussed.Comment: Accepted to AJ. Final proof-edited version: references added, discussion of G98 revised in sections 4.3 and 5.

Barkhausen Noise in a Relaxor Ferroelectric

Barkhausen noise, including both periodic and aperiodic components, is found in and near the relaxor regime of a familiar relaxor ferroelectric, PbMg$_{1/3}$Nb$_{2/3}$O$_3$, driven by a periodic electric field. The temperature dependences of both the amplitude and spectral form show that the size of the coherent dipole moment changes shrink as the relaxor regime is entered, contrary to expectations based on some simple models.Comment: 4 pages RevTeX4, 5 figures; submitted to Phys Rev Let

Anomalous Noise in the Pseudogap Regime of YBa2_2Cu3_3O7−δ_{7-\delta}

An unusual noise component is found near and below about 250 K in the normal state of underdoped YBCO and Ca-YBCO films. This noise regime, unlike the more typical noise above 250 K, has features expected for a symmetry-breaking collective electronic state. These include large individual fluctuators, a magnetic sensitivity, and aging effects. A possible interpretation in terms of fluctuating charge nematic order is presented.Comment: 4 pages, 4 figure

Ethnicity, educational attainment, and physical health of older adults in the United States

ObjectiveMinorities’ diminished returns theory suggests that socioeconomic status (SES) resources generate fewer health benefits for racial and ethnic minority groups, compared to the majority group. The current study aimed to compare Hispanic and non‐Hispanic white older adults for the association between educational attainment and poor physical self‐rated health (SRH).MethodsThe first wave of the University of Michigan National Poll on Healthy Aging (UM‐NPHA) included 1820 older adults who were 50‐80 years old and were either non‐Hispanic white (n = 1618) or Hispanic white (n = 202). The main independent variable of interest was educational attainment. The main dependent variable of interest was poor physical SRH. Gender, age, marital status, and employment status were covariates. Ethnicity was the focal effect modifier.ResultsOverall, higher level of educational attainment was associated with better physical SRH. A significant interaction was found between ethnicity and level of educational attainment, which was indicative of a smaller physical SRH gain due to high educational attainment for Hispanic white compared to non‐Hispanic white older adults. In ethnic‐specific models, we found evidence suggesting that high educational attainment reduced the odds of poor physical SRH for non‐Hispanic whites but not for Hispanic whites.ConclusionCompared to non‐Hispanic whites, Hispanic whites gain less physical SRH benefits from their educational attainment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149760/1/agm212050_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149760/2/agm212050.pd