Common and Distinct Roles of Juvenile Hormone Signaling Genes in Metamorphosis of Holometabolous and Hemimetabolous Insects

Insect larvae metamorphose to winged and reproductive adults either directly (hemimetaboly) or through an intermediary pupal stage (holometaboly). In either case juvenile hormone (JH) prevents metamorphosis until a larva has attained an appropriate phase of development. In holometabolous insects, JH acts through its putative receptor Methoprene-tolerant (Met) to regulate Krüppel-homolog 1 (Kr-h1) and Broad-Complex (BR-C) genes. While Met and Kr-h1 prevent precocious metamorphosis in pre-final larval instars, BR-C specifies the pupal stage. How JH signaling operates in hemimetabolous insects is poorly understood. Here, we compare the function of Met, Kr-h1 and BR-C genes in the two types of insects. Using systemic RNAi in the hemimetabolous true bug, Pyrrhocoris apterus, we show that Met conveys the JH signal to prevent premature metamorphosis by maintaining high expression of Kr-h1. Knockdown of either Met or Kr-h1 (but not of BR-C) in penultimate-instar Pyrrhocoris larvae causes precocious development of adult color pattern, wings and genitalia. A natural fall of Kr-h1 expression in the last larval instar normally permits adult development, and treatment with an exogenous JH mimic methoprene at this time requires both Met and Kr-h1 to block the adult program and induce an extra larval instar. Met and Kr-h1 therefore serve as JH-dependent repressors of deleterious precocious metamorphic changes in both hemimetabolous and holometabolous juveniles, whereas BR-C has been recruited for a new role in specifying the holometabolous pupa. These results show that despite considerable evolutionary distance, insects with diverse developmental strategies employ a common-core JH signaling pathway to commit to adult morphogenesis

The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity

Citation: Hanschen, E. R., Marriage, T. N., Ferris, P. J., Hamaji, T., Toyoda, A., Fujiyama, A., . . . Olson, B. (2016). The Gonium pectorale genome demonstrates co-option of cell cycle regulation during the evolution of multicellularity. Nature Communications, 7, 10. doi:10.1038/ncomms11370Additional Authors: Anderson, J.;Bakaric, R.;Luria, V.;Karger, A.;Kirschner, M. W.;Durand, P. M.;Michod, R. E.;Nozaki, H.The transition to multicellularity has occurred numerous times in all domains of life, yet its initial steps are poorly understood. The volvocine green algae are a tractable system for understanding the genetic basis of multicellularity including the initial formation of cooperative cell groups. Here we report the genome sequence of the undifferentiated colonial alga, Gonium pectorale, where group formation evolved by co-option of the retinoblastoma cell cycle regulatory pathway. Significantly, expression of the Gonium retinoblastoma cell cycle regulator in unicellular Chlamydomonas causes it to become colonial. The presence of these changes in undifferentiated Gonium indicates extensive group-level adaptation during the initial step in the evolution of multicellularity. These results emphasize an early and formative step in the evolution of multicellularity, the evolution of cell cycle regulation, one that may shed light on the evolutionary history of other multicellular innovations and evolutionary transitions

Landau level mixing and spin degeneracy in the quantum Hall effect

We study dynamics of electrons in a magnetic field using a network model with two channels per link with random mixing in a random intrachannel potential; the channels represent either two Landau levels or two spin states. We consider channel mixing as function of the energy separation of the two extended states and show that its effect changes from repulsion to attraction as the energy separation increases. For two Landau levels this leads to level floating at low magnetic fields while for Zeeman split spin states we predict level attraction at high magnetic fields, accounting for ESR data. We also study random mixing of two degenerate channels, while the intrachannel potential is periodic (non-random). We find a single extended state with a localization exponent $\nu\approx 1.1$ for real scattering at nodes; the general case has also a single extended state, though the localized nature of nearby states sets in at unusually large scales.Comment: 18 pages, 11 tex-files and 1 ps-file of figure

The random magnetic flux problem in a quantum wire

The random magnetic flux problem on a lattice and in a quasi one-dimensional (wire) geometry is studied both analytically and numerically. The first two moments of the conductance are obtained analytically. Numerical simulations for the average and variance of the conductance agree with the theory. We find that the center of the band $\epsilon=0$ plays a special role. Away from $\epsilon=0$, transport properties are those of a disordered quantum wire in the standard unitary symmetry class. At the band center $\epsilon=0$, the dependence on the wire length of the conductance departs from the standard unitary symmetry class and is governed by a new universality class, the chiral unitary symmetry class. The most remarkable property of this new universality class is the existence of an even-odd effect in the localized regime: Exponential decay of the average conductance for an even number of channels is replaced by algebraic decay for an odd number of channels.Comment: 16 pages, RevTeX; 9 figures included; to appear in Physical Review

Crossover from the chiral to the standard universality classes in the conductance of a quantum wire with random hopping only

The conductance of a quantum wire with off-diagonal disorder that preserves a sublattice symmetry (the random hopping problem with chiral symmetry) is considered. Transport at the band center is anomalous relative to the standard problem of Anderson localization both in the diffusive and localized regimes. In the diffusive regime, there is no weak-localization correction to the conductance and universal conductance fluctuations are twice as large as in the standard cases. Exponential localization occurs only for an even number of transmission channels in which case the localization length does not depend on whether time-reversal and spin rotation symmetry are present or not. For an odd number of channels the conductance decays algebraically. Upon moving away from the band center transport characteristics undergo a crossover to those of the standard universality classes of Anderson localization. This crossover is calculated in the diffusive regime.Comment: 22 pages, 9 figure

Sequence Analysis of the Genome of an Oil-Bearing Tree, Jatropha curcas L.

The whole genome of Jatropha curcas was sequenced, using a combination of the conventional Sanger method and new-generation multiplex sequencing methods. Total length of the non-redundant sequences thus obtained was 285 858 490 bp consisting of 120 586 contigs and 29 831 singlets. They accounted for ∼95% of the gene-containing regions with the average G + C content was 34.3%. A total of 40 929 complete and partial structures of protein encoding genes have been deduced. Comparison with genes of other plant species indicated that 1529 (4%) of the putative protein-encoding genes are specific to the Euphorbiaceae family. A high degree of microsynteny was observed with the genome of castor bean and, to a lesser extent, with those of soybean and Arabidopsis thaliana. In parallel with genome sequencing, cDNAs derived from leaf and callus tissues were subjected to pyrosequencing, and a total of 21 225 unigene data have been generated. Polymorphism analysis using microsatellite markers developed from the genomic sequence data obtained was performed with 12 J. curcas lines collected from various parts of the world to estimate their genetic diversity. The genomic sequence and accompanying information presented here are expected to serve as valuable resources for the acceleration of fundamental and applied research with J. curcas, especially in the fields of environment-related research such as biofuel production. Further information on the genomic sequences and DNA markers is available at http://www.kazusa.or.jp/jatropha/

Cathepsin L Inhibition Prevents Murine Autoimmune Diabetes via Suppression of CD8+ T Cell Activity

Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet b cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell–mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice. Methods and Findings: Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8 + T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8 + T cells in the pancreatic islets through controlling dipeptidyl peptidase I activity. Moreover, the gene targeting for cathepsin L with application of in vivo siRNA administration successfully prevented CY-induced diabetes of NOD mice. Finally, cathepsin L mRNA expression of peripheral CD8 + T cells from NOD mice developing spontaneous T1D was significantly increased compared with that from control mice. Conclusions: Our results identified a novel function of cathepsin L as an enzyme whose activity is essential for the progression of CD8 + T cell-mediated autoimmune diabetes, and inhibition of cathepsin L as a powerful therapeutic strateg

The living microarray: a high-throughput platform for measuring transcription dynamics in single cells

<p>Abstract</p> <p>Background</p> <p>Current methods of measuring transcription in high-throughput have led to significant improvements in our knowledge of transcriptional regulation and Systems Biology. However, endpoint measurements obtained from methods that pool populations of cells are not amenable to studying time-dependent processes that show cell heterogeneity.</p> <p>Results</p> <p>Here we describe a high-throughput platform for measuring transcriptional changes in real time in single mammalian cells. By using reverse transfection microarrays we are able to transfect fluorescent reporter plasmids into 600 independent clusters of cells plated on a single microscope slide and image these clusters every 20 minutes. We use a fast-maturing, destabilized and nuclear-localized reporter that is suitable for automated segmentation to accurately measure promoter activity in single cells. We tested this platform with synthetic drug-inducible promoters that showed robust induction over 24 hours. Automated segmentation and tracking of over 11 million cell images during this period revealed that cells display substantial heterogeneity in their responses to the applied treatment, including a large proportion of transfected cells that do not respond at all.</p> <p>Conclusions</p> <p>The results from our single-cell analysis suggest that methods that measure average cellular responses, such as DNA microarrays, RT-PCR and chromatin immunoprecipitation, characterize a response skewed by a subset of cells in the population. Our method is scalable and readily adaptable to studying complex systems, including cell proliferation, differentiation and apoptosis.</p

The Acute Environment, Rather than T Cell Subset Pre-Commitment, Regulates Expression of the Human T Cell Cytokine Amphiregulin

Cytokine expression patterns of T cells can be regulated by pre-commitment to stable effector phenotypes, further modification of moderately stable phenotypes, and quantitative changes in cytokine production in response to acute signals. We showed previously that the epidermal growth factor family member Amphiregulin is expressed by T cell receptor-activated mouse CD4 T cells, particularly Th2 cells, and helps eliminate helminth infection. Here we report a detailed analysis of the regulation of Amphiregulin expression by human T cell subsets. Signaling through the T cell receptor induced Amphiregulin expression by most or all T cell subsets in human peripheral blood, including naive and memory CD4 and CD8 T cells, Th1 and Th2 in vitro T cell lines, and subsets of memory CD4 T cells expressing several different chemokine receptors and cytokines. In these different T cell types, Amphiregulin synthesis was inhibited by an antagonist of protein kinase A, a downstream component of the cAMP signaling pathway, and enhanced by ligands that increased cAMP or directly activated protein kinase A. Prostaglandin E2 and adenosine, natural ligands that stimulate adenylyl cyclase activity, also enhanced Amphiregulin synthesis while reducing synthesis of most other cytokines. Thus, in contrast to mouse T cells, Amphiregulin synthesis by human T cells is regulated more by acute signals than pre-commitment of T cells to a particular cytokine pattern. This may be appropriate for a cytokine more involved in repair than attack functions during most inflammatory responses