Functional Evolution of a cis-Regulatory Module

Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules

A Finite Element Test Bed for Diffraction Tomography

Finite element analysis methods have been successfully applied to the study of ultrasonic wave propagation in elastic solids [1–4]. As a natural part of such numerical solutions. displacements are predicted for every node of the spatial discretization describing the solids geometry and at every instant of time in the temporal discretization used to define the pulse propagation through the material. All of the data constitute a solution to the forward problem and can be used to visualize wavefront propagation and interactions with defects, thus predicting displacement signals at any point in or on the solid

Characterization of the monocyte-specific esterase (MSE) gene

Carboxylic esterases are widely distributed in hematopoietic cells. Monocytes express the esterase isoenzyme (termed 'monocyte-specific esterase', MSE) that can be inhibited by NaF in the alpha-naphthyl acetate cytochemical staining. We examined the expression of MSE in normal cells and primary and cultured leukemia-lymphoma cells. The MSE protein was demonstrated by isoelectric focusing (IEF); MSE mRNA expression was investigated by Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The following samples were positive for MSE protein and Northern mRNA expression: 20/24 monocytic, 4/32 myeloid, and 1/20 erythroid-megakaryocytic leukemia cell lines, but none of the 112 lymphoid leukemia or lymphoma cell lines; of the normal purified cell populations only the monocytes were positive whereas, T, B cells, and granulocytes were negative; of primary acute (myelo) monocytic leukemia cells (CD14-positive, FAB M4/M5 morphology) 14/20 were Northern mRNA and 11/14 IEF protein positive. RT-PCR revealed MSE expression in 29/49 Northern-negative lymphoid leukemia-lymphoma cell lines. The RT-PCR signals in monocytic cell lines were on average 50-fold stronger than the mostly weak trace expression in lymphoid specimens. On treatment with various biomodulators, only all-trans retinoic acid significantly upregulated MSE message and protein levels but could not induce new MSE expression in several leukemia cell lines; lipopolysaccharide and interferon-gamma increased MSE expression in normal monocytes. Analysis of DNA methylation with sensitive restriction enzymes showed no apparent regulation of gene expression by differential methylation; the MSE gene is evolutionarily conserved among mammalian species; the half-life of the human MSE transcripts was about 5-6 h. The extent of MSE expression varied greatly among different monocytic leukemia samples. However, the MSE overexpression in a significant number of specimens was not associated with gene amplification, gross structural rearrangements or point mutations within the cDNA region. Taken together, the results suggest that MSE expression is not absolutely specific for, but strongly associated with cells of the monocytic lineage; MSE is either not expressed at all or expressed at much lower levels in cells from other lineages. The biological significance, if any, of rare MSE messages in lymphoid cells detectable only by the hypersensitive RT-PCR remains unclear. Further studies on the regulation of this gene and on the physiological function of the enzyme will no doubt be informative with respect to its striking overexpression in some malignant cells and to a possible role in the pathobiology of monocytic leukemias

On osp(2|2) conformal field theories

We study the conformal field theories corresponding to current superalgebras $osp(2|2)^{(1)}_k$ and $osp(2|2)^{(2)}_k$. We construct the free field realizations, screen currents and primary fields of these current superalgebras at general level $k$. All the results for $osp(2|2)^{(2)}_k$ are new, and the results for the primary fields of $osp(2|2)^{(1)}_k$ also seem to be new. Our results are expected to be useful in the supersymmetric approach to Gaussian disordered systems such as random bond Ising model and Dirac model.Comment: LaTex file 20 pages; Title changed and modifications mad

On the Wake Structure in Streaming Complex Plasmas

The theoretical description of complex (dusty) plasmas requires multiscale concepts that adequately incorporate the correlated interplay of streaming electrons and ions, neutrals, and dust grains. Knowing the effective dust-dust interaction, the multiscale problem can be effectively reduced to a one-component plasma model of the dust subsystem. The goal of the present publication is a systematic evaluation of the electrostatic potential distribution around a dust grain in the presence of a streaming plasma environment by means of two complementary approaches: (i) a high precision computation of the dynamically screened Coulomb potential from the dynamic dielectric function, and (ii) full 3D particle-in-cell simulations, which self-consistently include dynamical grain charging and non-linear effects. The applicability of these two approaches is addressed

The Effect of Focusing and Caustics on Exit Phenomena in Systems Lacking Detailed Balance

We study the trajectories followed by a particle subjected to weak noise when escaping from the domain of attraction of a stable fixed point. If detailed balance is absent, a _focus_ may occur along the most probable exit path, leading to a breakdown of symmetry (if present). The exit trajectory bifurcates, and the exit location distribution may become `skewed' (non-Gaussian). The weak-noise asymptotics of the mean escape time are strongly affected. Our methods extend to the study of skewed exit location distributions in stochastic models without symmetry.Comment: REVTEX macros (latest version). Two accompanying PS figures, one of which is large (over 600K unpacked

Functional Evolution of a <i>cis-</i>Regulatory Module

Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules.</p

Social creatures: model animal systems for studying the neuroendocrine mechanisms of social behaviour

Work was supported by grants awarded to ML (BBSRC BB/S000224/1), OJB (BO 1958/8-2, GRK 2174), KEB (Wellcome Trust 109614/Z/15/Z, MRC MR/N004574/1), AJ (BBSRC BB/S000801) and GL (Israel Science Foundation #1511/16; United States-Israel Binational Science Foundation #2017325; Nella and Leon Benoziyo Center for Neurological Diseases, Richard F. Goodman Yale/Weizmann Exchange Program and Estate of Emile Mimran).The interaction of animals with conspecifics, termed social behaviour, has a major impact on the survival of many vertebrate species. Neuropeptide hormones modulate the underlying physiology that governs social interactions, and many findings concerning the neuroendocrine mechanisms of social behaviours have been extrapolated from animal models to humans. Neurones expressing neuropeptides show similar distribution patterns within the hypothalamic nucleus, even when evolutionarily distant species are compared. During evolution, hypothalamic neuropeptides and releasing hormones have retained not only their structures, but also their biological functions, including their effects on behaviour. Here, we review the current understanding of the mechanisms of social behaviours in several classes of animals, such as worms, insects and fish, as well as laboratory, wild and domesticated mammals.Publisher PDFPeer reviewe

Resonant tunneling and the multichannel Kondo problem: the quantum Brownian motion description

We study mesoscopic resonant tunneling as well as multichannel Kondo problems by mapping them to a first-quantized quantum mechanical model of a particle moving in a multi-dimensional periodic potential with Ohmic dissipation. From a renormalization group analysis, we obtain phase diagrams of the quantum Brownian motion model with various lattice symmetries. For a symmorphic lattice, there are two phases at T=0: a localized phase in which the particle is trapped in a potential minimum, and a free phase in which the particle is unaffected by the periodic potential. For a non-symmorphic lattice, however, there may be an additional intermediate phase in which the particle is neither localized nor completely free. The fixed point governing the intermediate phase is shown to be identical to the well-known multichannel Kondo fixed point in the Toulouse limit as well as the resonance fixed point of a quantum dot model and a double-barrier Luttinger liquid model. The mapping allows us to compute the fixed-poing mobility $\mu^*$ of the quantum Brownian motion model exactly, using known conformal-field-theory results of the Kondo problem. From the mobility, we find that the peak value of the conductance resonance of a spin-1/2 quantum dot problem is given by $e^2/2h$. The scaling form of the resonance line shape is predicted