Leptotene/Zygotene Chromosome Movement Via the SUN/KASH Protein Bridge in Caenorhabditis elegans

The Caenorhabditis elegans inner nuclear envelope protein matefin/SUN-1 plays a conserved, pivotal role in the process of genome haploidization. CHK-2–dependent phosphorylation of SUN-1 regulates homologous chromosome pairing and interhomolog recombination in Caenorhabditis elegans. Using time-lapse microscopy, we characterized the movement of matefin/SUN-1::GFP aggregates (the equivalent of chromosomal attachment plaques) and showed that the dynamics of matefin/SUN-1 aggregates remained unchanged throughout leptonene/zygotene, despite the progression of pairing. Movement of SUN-1 aggregates correlated with chromatin polarization. We also analyzed the requirements for the formation of movement-competent matefin/SUN-1 aggregates in the context of chromosome structure and found that chromosome axes were required to produce wild-type numbers of attachment plaques. Abrogation of synapsis led to a deceleration of SUN-1 aggregate movement. Analysis of matefin/SUN-1 in a double-strand break deficient mutant revealed that repair intermediates influenced matefin/SUN-1 aggregate dynamics. Investigation of movement in meiotic regulator mutants substantiated that proper orchestration of the meiotic program and effective repair of DNA double-strand breaks were necessary for the wild-type behavior of matefin/SUN-1 aggregates

Hippocampal Volume Reduction in Congenital Central Hypoventilation Syndrome

Children with congenital central hypoventilation syndrome (CCHS), a genetic disorder characterized by diminished drive to breathe during sleep and impaired CO2 sensitivity, show brain structural and functional changes on magnetic resonance imaging (MRI) scans, with impaired responses in specific hippocampal regions, suggesting localized injury

A Yeast Two-Hybrid Screen for SYP-3 Interactors Identifies SYP-4, a Component Required for Synaptonemal Complex Assembly and Chiasma Formation in Caenorhabditis elegans Meiosis

The proper assembly of the synaptonemal complex (SC) between homologs is critical to ensure accurate meiotic chromosome segregation. The SC is a meiotic tripartite structure present from yeast to humans, comprised of proteins assembled along the axes of the chromosomes and central region (CR) proteins that bridge the two chromosome axes. Here we identify SYP-4 as a novel structural component of the SC in Caenorhabditis elegans. SYP-4 interacts in a yeast two-hybrid assay with SYP-3, one of components of the CR of the SC, and is localized at the interface between homologs during meiosis. SYP-4 is essential for the localization of SYP-1, SYP-2, and SYP-3 CR proteins onto chromosomes, thereby playing a crucial role in the stabilization of pairing interactions between homologous chromosomes. In the absence of SYP-4, the levels of recombination intermediates, as indicated by RAD-51 foci, are elevated in mid-prophase nuclei, and crossover recombination events are significantly reduced. The lack of chiasmata observed in syp-4 mutants supports the elevated levels of chromosome nondisjunction manifested in high embryonic lethality. Altogether our findings place SYP-4 as a central player in SC formation and broaden our understanding of the structure of the SC and its assembly

Discovering local patterns of co - evolution: computational aspects and biological examples

<p>Abstract</p> <p>Background</p> <p>Co-evolution is the process in which two (or more) sets of orthologs exhibit a similar or correlative pattern of evolution. Co-evolution is a powerful way to learn about the functional interdependencies between sets of genes and cellular functions and to predict physical interactions. More generally, it can be used for answering fundamental questions about the evolution of biological systems.</p> <p>Orthologs that exhibit a strong signal of co-evolution in a certain part of the evolutionary tree may show a mild signal of co-evolution in other branches of the tree. The major reasons for this phenomenon are noise in the biological input, genes that gain or lose functions, and the fact that some measures of co-evolution relate to rare events such as positive selection. Previous publications in the field dealt with the problem of finding sets of genes that co-evolved along an entire underlying phylogenetic tree, without considering the fact that often co-evolution is local.</p> <p>Results</p> <p>In this work, we describe a new set of biological problems that are related to finding patterns of <it>local </it>co-evolution. We discuss their computational complexity and design algorithms for solving them. These algorithms outperform other bi-clustering methods as they are designed specifically for solving the set of problems mentioned above.</p> <p>We use our approach to trace the co-evolution of fungal, eukaryotic, and mammalian genes at high resolution across the different parts of the corresponding phylogenetic trees. Specifically, we discover regions in the fungi tree that are enriched with positive evolution. We show that metabolic genes exhibit a remarkable level of co-evolution and different patterns of co-evolution in various biological datasets.</p> <p>In addition, we find that protein complexes that are related to gene expression exhibit non-homogenous levels of co-evolution across different parts of the <it>fungi </it>evolutionary line. In the case of mammalian evolution, signaling pathways that are related to <it>neurotransmission </it>exhibit a relatively higher level of co-evolution along the <it>primate </it>subtree.</p> <p>Conclusions</p> <p>We show that finding local patterns of co-evolution is a computationally challenging task and we offer novel algorithms that allow us to solve this problem, thus opening a new approach for analyzing the evolution of biological systems.</p

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa

Cross Section Measurements of High-pTp_T Dilepton Final-State Processes Using a Global Fitting Method

We present a new method for studying high-$p_T$ dilepton events ($e^{\pm}e^{\mp}$, $\mu^{\pm}\mu^{\mp}$, $e^{\pm}\mu^{\mp}$) and simultaneously extracting the production cross sections of $p\bar{p} \to t\bar{t}$, $p\bar{p} \to W^+W^-$, and p\bar{p} \to \ztt at a center-of-mass energy of $\sqrt{s} = 1.96$ TeV. We perform a likelihood fit to the dilepton data in a parameter space defined by the missing transverse energy and the number of jets in the event. Our results, which use $360 {\rm pb^{-1}}$ of data recorded with the CDF II detector at the Fermilab Tevatron Collider, are $\sigma(t\bar{t}) = 8.5_{-2.2}^{+2.7}$ pb, $\sigma(W^+W^-) = 16.3^{+5.2}_{-4.4}$ pb, and \sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R

Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Top Quark Mass Measurement from Dilepton Events at CDF II with the Matrix-Element Method

We describe a measurement of the top quark mass using events with two charged leptons collected by the CDF II detector from $p\bar{p}$ collisions with $\sqrt s = 1.96$ TeV at the Fermilab Tevatron. The likelihood in top mass is calculated for each event by convoluting the leading order matrix element describing $q\bar{q} \to t\bar{t} \to b\ell\nu_{\ell}\bar{b}\ell'\nu_{\ell'}$ with detector resolution functions. The presence of background events in the data sample is modeled using similar calculations involving the matrix elements for major background processes. In a data sample with integrated luminosity of 340 pb$^{-1}$, we observe 33 candidate events and measure $M_{top} = 165.2 \pm 6.1(\textrm{stat.}) \pm 3.4(\textrm{syst.}) \mathrm{~GeV}/c^2.$ This measurement represents the first application of this method to events with two charged leptons and is the most precise single measurement of the top quark mass in this channel.Comment: 21 pages, 14 figure