Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer

Proton-neutron pairing in the deformed BCS approach

We examine isovector and isoscalar proton-neutron pairing correlations for the ground state of even-even Ge isotopes with mass number A=64-76 within the deformed BCS approach. For N=Z 64Ge the BCS solution with only T=0 proton-neutron pairs is found. For other nuclear systems (N>Z) a coexistence of a T=0 and T=1 pairs in the BCS wave function is observed. A problem of fixing of strengths of isoscalar and isovector pairing interactions is addressed. A dependence of number of like and unlike pairs in the BCS ground state on the difference between number of neutrons and protons is discussed. We found that for nuclei with N much bigger than Z the effect of proton-neutron pairing is small but not negligible.Comment: 24 pages, 6 figure

Do Lognormal Column-Density Distributions in Molecular Clouds Imply Supersonic Turbulence?

Recent observations of column densities in molecular clouds find lognormal distributions with power-law high-density tails. These results are often interpreted as indications that supersonic turbulence dominates the dynamics of the observed clouds. We calculate and present the column-density distributions of three clouds, modeled with very different techniques, none of which is dominated by supersonic turbulence. The first star-forming cloud is simulated using smoothed particle hydrodynamics (SPH); in this case gravity, opposed only by thermal-pressure forces, drives the evolution. The second cloud is magnetically subcritical with subsonic turbulence, simulated using nonideal MHD; in this case the evolution is due to gravitationally-driven ambipolar diffusion. The third cloud is isothermal, self-gravitating, and has a smooth density distribution analytically approximated with a uniform inner region and an r^-2 profile at larger radii. We show that in all three cases the column-density distributions are lognormal. Power-law tails develop only at late times (or, in the case of the smooth analytic profile, for strongly centrally concentrated configurations), when gravity dominates all opposing forces. It therefore follows that lognormal column-density distributions are generic features of diverse model clouds, and should not be interpreted as being a consequence of supersonic turbulence.Comment: 6 pages, 6 figures, accepted for publication in MNRA

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Constraints on Three-Neutrino Mixing from Atmospheric and Reactor Data

Observations of atmospheric neutrinos are usually analyzed using the simplifying approximation that either $\nu_\mu \leftrightarrow \nu_\tau$ or $\nu_e \leftrightarrow \nu_\mu$ two-flavor mixing is relevant. Here we instead consider the data using the simplifying approximation that only one neutrino mass scale is relevant. This approximation is the minimal three-flavor notation that includes the two relevant two-flavor approximations. The constraints in the parameter space orthogonal to the usual, two-flavor analyses are studied.Comment: 15 pages, preprint IUHET-26

Diversity, host specialization, and geographic structure of filarial nematodes infecting Malagasy bats

We investigated filarial infection in Malagasy bats to gain insights into the diversity of these parasites and explore the factors shaping their distribution. Samples were obtained from 947 individual bats collected from 52 sites on Madagascar and representing 31 of the 44 species currently recognized on the island. Samples were screened for the presence of micro-and macro-parasites through both molecular and morphological approaches. Phylogenetic analyses showed that filarial diversity in Malagasy bats formed three main groups, the most common represented by Litomosa spp. infecting Miniopterus spp. (Miniopteridae); a second group infecting Pipistrellus cf. hesperidus (Vespertilionidae) embedded within the Litomosoides cluster, which is recognized herein for the first time from Madagascar; and a third group composed of lineages with no clear genetic relationship to both previously described filarial nematodes and found in M. griveaudi, Myotis goudoti, Neoromicia matroka (Vespertilionidae), Otomops madagascariensis (Molossidae), and Paratriaenops furculus (Hipposideridae). We further analyzed the infection rates and distribution pattern of Litomosa spp., which was the most diverse and prevalent filarial taxon in our sample. Filarial infection was disproportionally more common in males than females in Miniopterus spp., which might be explained by some aspect of roosting behavior of these cave-dwelling bats. We also found marked geographic structure in the three Litomosa clades, mainly linked to bioclimatic conditions rather than host-parasite associations. While this study demonstrates distinct patterns of filarial nematode infection in Malagasy bats and highlights potential drivers of associated geographic distributions, future work should focus on their alpha taxonomy and characterize arthropod vectors

Progress in neutrino oscillation searches and their implications

Neutrino Oscillation, in which a given flavour of neutrino transforms into another is a powerful tool for probing small neutrino masses. The intrinsic neutrino properties involved are neutrino mass squared difference $\Delta m^2$ and the mixing angle in vacuum $\theta$. In this talk I will summarize the progress that we have achieved in our search for neutrino oscillation with special emphasis on the recent results from the Sudbury Neutrino Observatory (SNO) on the measurement of solar neutrino fluxes. I will outline the current bounds on the neutrino masses and mixing parameters and discuss the major physics goals of future neutrino experiments in the context of the present picture.Comment: Plenary Talk, WHEPP-7, January 2002, published in Pramana, Vol. 60, 261, 200

Weak local rules for planar octagonal tilings

We provide an effective characterization of the planar octagonal tilings which admit weak local rules. As a corollary, we show that they are all based on quadratic irrationalities, as conjectured by Thang Le in the 90s.Comment: 23 pages, 6 figure