The genome of Romanomermis culicivorax:revealing fundamental changes in the core developmental genetic toolkit in Nematoda

Background: The genetics of development in the nematode Caenorhabditis elegans has been described in exquisite detail. The phylum Nematoda has two classes: Chromadorea (which includes C. elegans) and the Enoplea. While the development of many chromadorean species resembles closely that of C. elegans, enoplean nematodes show markedly different patterns of early cell division and cell fate assignment. Embryogenesis of the enoplean Romanomermis culicivorax has been studied in detail, but the genetic circuitry underpinning development in this species has not been explored. Results: We generated a draft genome for R. culicivorax and compared its gene content with that of C. elegans, a second enoplean, the vertebrate parasite Trichinella spiralis, and a representative arthropod, Tribolium castaneum. This comparison revealed that R. culicivorax has retained components of the conserved ecdysozoan developmental gene toolkit lost in C. elegans. T. spiralis has independently lost even more of this toolkit than has C. elegans. However, the C. elegans toolkit is not simply depauperate, as many novel genes essential for embryogenesis in C. elegans are not found in, or have only extremely divergent homologues in R. culicivorax and T. spiralis. Our data imply fundamental differences in the genetic programmes not only for early cell specification but also others such as vulva formation and sex determination. Conclusions: Despite the apparent morphological conservatism, major differences in the molecular logic of development have evolved within the phylum Nematoda. R. culicivorax serves as a tractable system to contrast C. elegans and understand how divergent genomic and thus regulatory backgrounds nevertheless generate a conserved phenotype. The R. culicivorax draft genome will promote use of this species as a research model

The effect of pair-instability mass loss on black-hole mergers

Context. Mergers of two stellar-origin black holes are a prime source of gravitational waves and are under intensive investigation. One crucial ingredient in their modeling has been neglected: pair-instability pulsation supernovae with associated severe mass loss may suppress the formation of massive black holes, decreasing black-hole-merger rates for the highest black-hole masses. Aims. We demonstrate the effects of pair-instability pulsation supernovae on merger rate and mass using populations of double black-hole binaries formed through the isolated binary classical evolution channel. Methods. The mass loss from pair-instability pulsation supernova is estimated based on existing hydrodynamical calculations. This mass loss is incorporated into the StarTrack population synthesis code. StarTrack is used to generate double black-hole populations with and without pair-instability pulsation supernova mass loss. Results. The mass loss associated with pair-instability pulsation supernovae limits the Population I/II stellar-origin black-hole mass to 50 M⊙, in tension with earlier predictions that the maximum black-hole mass could be as high as 100 M⊙. In our model, neutron stars form with mass 1−2 M⊙. We then encounter the first mass gap at 2−5 M⊙ with the compact object absence due to rapid supernova explosions, followed by the formation of black holes with mass 5−50 M⊙, with a second mass gap at 50−135 M⊙ created by pair-instability pulsation supernovae and by pair-instability supernovae. Finally, black holes with masses above 135 M⊙ may potentially form to arbitrarily high mass limited only by the extent of the initial mass function and the strength of stellar winds. Suppression of double black-hole-merger rates by pair-instability pulsation supernovae is negligible for our evolutionary channel. Our standard evolutionary model, with the inclusion of pair-instability pulsation supernovae and pair-instability supernovae, is fully consistent with the Laser Interferometric Gravitational-wave Observatory (LIGO) observations of black-hole mergers: GW150914, GW151226, and LVT151012. The LIGO results are inconsistent with high (≳ 400 km s-1) black hole (BH) natal kicks. We predict the detection of several, and up to as many as ~60, BH-BH mergers with a total mass of 10−150 M⊙ (most likely range: 20−80 M⊙) in the forthcoming ~60 effective days of the LIGO O2 observations, assuming the detectors reach the optimistic target O2 sensitivity

Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in S. cerevisiae

The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We have identified posttranslational modifications of S. cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants showed growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody we showed that the association of phosphorylated Cse4 with centromeres is increased in response to defective microtubule attachment or reduced cohesion. We determined that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 were reduced at centromeres in ipl1 strains in vivo and in vitro assays showed phosphorylation of Cse4 by Ipl1. Consistent with these results we observed that a phosphomimetic cse4-4SD mutant suppressed the temperature sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80 that are defective for chromosome biorientation. Furthermore, cell biology approaches using a GFP labeled chromosome showed that cse4-4SD suppressed chromosome segregation defects in dam1 spc34 strains. Based these results we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our study provides a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation

Trans-Relativistic Blast Waves in Supernovae as Gamma-Ray Burst Progenitors

We investigate the acceleration of shock waves to relativistic velocities in the outer layers of exploding stars. By concentrating the explosion energy in the outermost ejecta, such trans-relativistic blast waves can serve as the progenitors of gamma-ray bursts (GRBs); in particular, the ``baryon-loading'' problem that plagues many models of GRBs is circumvented. We present physically motivated and numerically validated analytic expressions to describe trans-relativistic blast waves in supernovae. We find that relativistic ejecta are enhanced in more centrally condensed envelopes, e.g., for radiative envelopes, when the luminosity approaches the Eddington limit. We present convenient formulae for estimating the relativistic ejecta from a given progenitor. We apply our analytic and numerical methods to a model of SN 1998bw, finding significantly enhanced relativistic ejecta compared to previous studies. We propose that GRB 980425 is associated with SN 1998bw and may have resulted from an approximately spherical explosion producing ~10^-6 M_sun of mildly relativistic ejecta with mean Lorentz factor ~2, which then interacted with a dense circumstellar wind with mass loss rate ~few x 10^-4 M_sun/yr. A highly asymmetric explosion is not required. An extreme model of ``hypernova'' explosions in massive stars is able to account for the energetics and relativistic ejecta velocities required by many of the observed cosmological GRBs. We present simplified models of explosions resulting from accretion-induced collapse of white dwarfs and phase transitions of neutron stars. While we find increased energies in relativistic ejecta compared to previous studies, these explosions are unlikely to be observed at cosmological distances with current detectors. (abridged)Comment: Accepted to ApJ; minor changes from previous version; 41 pages (including 12 figures

The Extreme Hosts of Extreme Supernovae

We use GALEX ultraviolet (UV) and optical integrated photometry of the hosts of seventeen luminous supernovae (LSNe, having peak M_V < -21) and compare them to a sample of 26,000 galaxies from a cross-match between the SDSS DR4 spectral catalog and GALEX interim release 1.1. We place the LSNe hosts on the galaxy NUV-r versus M_r color magnitude diagram (CMD) with the larger sample to illustrate how extreme they are. The LSN hosts appear to favor low-density regions of the galaxy CMD falling on the blue edge of the blue cloud toward the low luminosity end. From the UV-optical photometry, we estimate the star formation history of the LSN hosts. The hosts have moderately low star formation rates (SFRs) and low stellar masses (M_*) resulting in high specific star formation rates (sSFR). Compared with the larger sample, the LSN hosts occupy low-density regions of a diagram plotting sSFR versus M_* in the area having higher sSFR and lower M_*. This preference for low M_*, high sSFR hosts implies the LSNe are produced by an effect having to do with their local environment. The correlation of mass with metallicity suggests that perhaps wind-driven mass loss is the factor that prevents LSNe from arising in higher-mass, higher-metallicity hosts. The massive progenitors of the LSNe (>100 M_sun), by appearing in low-SFR hosts, are potential tests for theories of the initial mass function that limit the maximum mass of a star based on the SFR.Comment: 8 pages, 3 figures, 2 tables, accepted to ApJ, amended references and updated SN designation

Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies

<p>Abstract</p> <p>Background</p> <p>Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR) are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers.</p> <p>Methods</p> <p>Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses.</p> <p>Results</p> <p>We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76%) of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72%) and 27% had only low levels of expression.</p> <p>Conclusions</p> <p>Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in treatment of this disease by providing new reagents to study the protein expression of the human PRLR.</p

The genome of a songbird

The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chickenthe only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat- based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. © 2010 Macmillan Publishers Limited. All rights reserved

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse—more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.National Science Foundation (U.S.) (NSF grant DEB-0920892)National Science Foundation (U.S.) (NSF grant DEB-0844624)National Human Genome Research Institute (U.S.