Probing DNA conformational changes with high temporal resolution by Tethered Particle Motion

The Tethered Particle Motion (TPM) technique informs about conformational changes of DNA molecules, e.g. upon looping or interaction with proteins, by tracking the Brownian motion of a particle probe tethered to a surface by a single DNA molecule and detecting changes of its amplitude of movement. We discuss in this context the time resolution of TPM, which strongly depends on the particle-DNA complex relaxation time, i.e. the characteristic time it takes to explore its configuration space by diffusion. By comparing theory, simulations and experiments, we propose a calibration of TPM at the dynamical level: we analyze how the relaxation time grows with both DNA contour length (from 401 to 2080 base pairs) and particle radius (from 20 to 150~nm). Notably we demonstrate that, for a particle of radius 20~nm or less, the hydrodynamic friction induced by the particle and the surface does not significantly slow down the DNA. This enables us to determine the optimal time resolution of TPM in distinct experimental contexts which can be as short as 20~ms.Comment: Improved version, to appear in Physical Biology. 10 pages + 10 pages of supporting materia

Control of Pre-mRNA Splicing by the General Splicing Factors PUF60 and U2AF65

Pre-mRNA splicing is a crucial step in gene expression, and accurate recognition of splice sites is an essential part of this process. Splice sites with weak matches to the consensus sequences are common, though it is not clear how such sites are efficiently utilized. Using an in vitro splicing-complementation approach, we identified PUF60 as a factor that promotes splicing of an intron with a weak 3' splice-site. PUF60 has homology to U2AF(65), a general splicing factor that facilitates 3' splice-site recognition at the early stages of spliceosome assembly. We demonstrate that PUF60 can functionally substitute for U2AF(65)in vitro, but splicing is strongly stimulated by the presence of both proteins. Reduction of either PUF60 or U2AF(65) in cells alters the splicing pattern of endogenous transcripts, consistent with the idea that regulation of PUF60 and U2AF(65) levels can dictate alternative splicing patterns. Our results indicate that recognition of 3' splice sites involves different U2AF-like molecules, and that modulation of these general splicing factors can have profound effects on splicing

Critical exponents at the ferromagnetic transition in tetrakis(diethylamino)ethylene-C60_{60} (TDAE-C60_{60})

Critical exponents at the ferromagnetic transition were measured for the first time in an organic ferromagnetic material tetrakis(dimethylamino)ethylene fullerene[60] (TDAE-C$_{60}$). From a complete magnetization-temperature-field data set near $T_{c}=16.1\pm 0.05,$ we determine the susceptibility and magnetization critical exponents $\gamma =1.22\pm 0.02$ and $\beta =0.75 \pm 0.03$ respectively, and the field vs. magnetization exponent at $T_{c}$ of $\delta =2.28\pm 0.14$. Hyperscaling is found to be violated by $\Omega \equiv d^{\prime}-d \approx -1/4$, suggesting that the onset of ferromagnetism can be related to percolation of a particular contact configuration of C$_{60}$ molecular orientations.Comment: 5 pages, including 3 figures; to appear in Phys. Rev. Let

Gate-induced band ferromagnetism in an organic polymer

We propose that a chain of five-membered rings (polyaminotriazole) should be ferromagnetic with an appropriate doping that is envisaged to be feasible with an FET structure. The ferromagnetism is confirmed by a spin density functional calculation, which also shows that ferromagnetism survives the Peierls instability. We explain the magnetism in terms of Mielke and Tasaki's flat-band ferromagnetism with the Hubbard model. This opens a new possibility of band ferromagnetism in purely organic polymers.Comment: 4 pages, 7 figure

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

Ferromagnetism and giant magnetoresistance in the rare earth fullerides Eu6-xSrxC60

We have studied crystal structure, magnetism and electric transport properties of a europium fulleride Eu6C60 and its Sr-substituted compounds, Eu6-xSrxC60. They have a bcc structure, which is an isostructure of other M6C60 (M represents an alkali atom or an alkaline earth atom). Magnetic measurements revealed that magnetic moment is ascribed to the divalent europium atom with S = 7/2 spin, and a ferromagnetic transition was observed at TC = 10 - 14 K. In Eu6C60, we also confirm the ferromagnetic transition by heat capacity measurement. The striking feature in Eu6-xSrxC60} is very large negative magnetoresistance at low temperature; the resistivity ratio \rho(H = 9 T)/\rho(H = 0 T) reaches almost 10^{-3} at 1 K in Eu6C60. Such large magnetoresistance is the manifestation of a strong pi-f interaction between conduction carriers on C60 and 4f electrons of Eu.Comment: 5 pages, 4 figure

Personality trait development in midlife: exploring the impact of psychological turning points

This study examined long-term personality trait development in midlife and explored the impact of psychological turning points on personality change. Selfdefined psychological turning points reflect major changes in the ways people think or feel about an important part of their life, such as work, family, and beliefs about themselves and about the world. This study used longitudinal data from the Midlife in the US survey to examine personality trait development in adults aged 40–60 years. The Big Five traits were assessed in 1995 and 2005 by means of self-descriptive adjectives. Seven types of self-identified psychological turning points were obtained in 1995. Results indicated relatively high stability with respect to rankorders and mean-levels of personality traits, and at the same time reliable individual differences in change. This implies that despite the relative stability of personality traits in the overall sample, some individuals show systematic deviations from the sample mean-levels. Psychological turning points in general showed very little influence on personality trait change, although some effects were found for specific types of turning points that warrant further research, such as discovering that a close friend or relative was a much better person than one thought they were

Superconductivity in Fullerides

Experimental studies of superconductivity properties of fullerides are briefly reviewed. Theoretical calculations of the electron-phonon coupling, in particular for the intramolecular phonons, are discussed extensively. The calculations are compared with coupling constants deduced from a number of different experimental techniques. It is discussed why the A_3 C_60 are not Mott-Hubbard insulators, in spite of the large Coulomb interaction. Estimates of the Coulomb pseudopotential $\mu^*$, describing the effect of the Coulomb repulsion on the superconductivity, as well as possible electronic mechanisms for the superconductivity are reviewed. The calculation of various properties within the Migdal-Eliashberg theory and attempts to go beyond this theory are described.Comment: 33 pages, latex2e, revtex using rmp style, 15 figures, submitted to Review of Modern Physics, more information at http://radix2.mpi-stuttgart.mpg.de/fullerene/fullerene.htm

Non-Markovian polymer reaction kinetics

Describing the kinetics of polymer reactions, such as the formation of loops and hairpins in nucleic acids or polypeptides, is complicated by the structural dynamics of their chains. Although both intramolecular reactions, such as cyclization, and intermolecular reactions have been studied extensively, both experimentally and theoretically, there is to date no exact explicit analytical treatment of transport-limited polymer reaction kinetics, even in the case of the simplest (Rouse) model of monomers connected by linear springs. We introduce a new analytical approach to calculate the mean reaction time of polymer reactions that encompasses the non-Markovian dynamics of monomer motion. This requires that the conformational statistics of the polymer at the very instant of reaction be determined, which provides, as a by-product, new information on the reaction path. We show that the typical reactive conformation of the polymer is more extended than the equilibrium conformation, which leads to reaction times significantly shorter than predicted by the existing classical Markovian theory.Comment: Main text (7 pages, 5 figures) + Supplemantary Information (13 pages, 2 figures

Entrepreneurs’ age, institutions, and social value creation goals: a multi-country study

This study explores the relationship between an entrepreneur's age and his/her social value creation goals. Building on the lifespan developmental psychology literature and institutional theory, we hypothesize a U-shaped relationship between entrepreneurs’ age and their choice to create social value through their ventures, such that younger and older entrepreneurs create more social value with their businesses while middle age entrepreneurs are relatively more economically and less socially oriented with their ventures. We further hypothesize that the quality of a country’s formal institutions in terms of economic, social, and political freedom steepen the U-shaped relationship between entrepreneurs’ age and their choice to pursue social value creation as supportive institutional environments allow entrepreneurs to follow their age-based preferences. We confirm our predictions using multilevel mixed-effects linear regressions on a sample of over 15,000 entrepreneurs (aged between 18 and 64 years) in 45 countries from Global Entrepreneurship Monitor data. The findings are robust to several alternative specifications. Based on our findings, we discuss implications for theory and practice, and we propose future research directions