Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans

Ferro-electric phase transition in a polar liquid and the nature of \lambda-transition in supercooled water

We develop a series of approximations to calculate free energy of a polar liquid. We show that long range nature of dipole interactions between the molecules leads to para-electric state instability at low temperatures and to a second-order phase transition. We establish the transition temperature, T_{c}, both within mean field and ring diagrams approximation and show that the ferro-electric transition may play an important role explaining a number of peculiar properties of supercooled water, such as weak singularity of dielectric constant as well as to a large extent anomalous density behavior. Finally we discuss the role of fluctuations, shorter range forces and establish connections with phenomenological models of polar liquids.Comment: 5 pages, 1 eps figure, density anomaly at T=4C analysis adde

Parent-of-origin effects on nuclear chromatin organization and behavior in a Drosophila model for Williams–Beuren Syndrome

Prognosis of neuropsychiatric disorders in progeny requires consideration of individual (1) parent-of-origin effects (POEs) relying on (2) the nerve cell nuclear 3D chromatin architecture and (3) impact of parent-specific miRNAs. Additionally, the shaping of cognitive phenotypes in parents depends on both learning acquisition and forgetting, or memory erasure. These processes are independent and controlled by different signal cascades: the first is cAMPdependent, the second relies on actin remodeling by small GTPase Rac1 – LIMK1 (LIM-kinase 1). Simple experimental model systems such as Drosophila help probe the causes and consequences leading to human neurocognitive pathologies. Recently, we have developed a Drosophila model for Williams–Beuren Syndrome (WBS): a mutant agnts3 of the agnostic locus (X:11AB) harboring the dlimk1 gene. The agnts3 mutation drastically increases the frequency of ectopic contacts (FEC) in specific regions of intercalary heterochromatin, suppresses learning/memory and affects locomotion. As is shown in this study, the polytene X chromosome bands in reciprocal hybrids between agnts3 and the wild type strain Berlin are heterogeneous in modes of FEC regulation depending either on maternal or paternal gene origin. Bioinformatic analysis reveals that FEC between X:11AB and the other X chromosome bands correlates with the occurrence of short (~30 bp) identical DNA fragments partly homologous to Drosophila 372-bp satellite DNA repeat. Although learning acquisition in a conditioned courtship suppression paradigm is similar in hybrids, the middle-term memory formation shows patroclinic inheritance. Seemingly, this depends on changes in miR-974 expression. Several parameters of locomotion demonstrate heterosis. Our data indicate that the agnts3 locus is capable of trans-regulating gene activity via POEs on the chromatin nuclear organization, thereby affecting behavior

Medicine and improvement in the Scots Magazine; and Edinburgh Literary Miscellany, 1804-17

Megan Coyer’s chapter engages with periodical print as a vehicle for an improving medical culture in Scotland, concentrating on the second series of the Scots Magazine. Coyer demonstrates how the Scottish press often complemented improving civic initiatives like the Edinburgh Lunatic Asylum campaign. She focuses attention on the distinctive national dynamics associated with medical improvement efforts in early nineteenth-century Scotland, with the Scots Magazine ‘providing a public forum for the expression of a national medical identity’. This identity, as Coyer shows, had an ideology of improvement at its core. This work recovers the cultural significance of the Scots Magazine as ‘the third major player in popular periodical culture in Romantic-era Scotland’; a status overshadowed by the recent critical attention devoted to the second Edinburgh Review and Blackwood’s in Scottish Romantic studies. Coyer also shows how the efforts of public health reformers highlight the complexity of improvement as both a material and moral process. She argues that print efforts dedicated to improving public health represent a ‘discursive strand in the magazine identifying a lack of cleanliness … as a moral and material blight on an otherwise improving Scottish society’. This bringing together of moral and practical aspects of improvement in the Scots also finds expression in the magazine’s series of Scottish medical biographies, whose narratives, Coyer notes, provide ‘ideal exemplars of lives dedicated to a culture of improvement’

Nucleologenesis in the Caenorhabditis elegans Embryo

In the Caenorhabditis elegans nematode, the oocyte nucleolus disappears prior to fertilization. We have now investigated the re-formation of the nucleolus in the early embryo of this model organism by immunostaining for fibrillarin and DAO-5, a putative NOLC1/Nopp140 homolog involved in ribosome assembly. We find that labeled nucleoli first appear in somatic cells at around the 8-cell stage, at a time when transcription of the embryonic genome begins. Quantitative analysis of radial positioning showed the nucleolus to be localized at the nuclear periphery in a majority of early embryonic nuclei. At the ultrastructural level, the embryonic nucleolus appears to be composed of a relatively homogenous core surrounded by a crescent-shaped granular structure. Prior to embryonic genome activation, fibrillarin and DAO-5 staining is seen in numerous small nucleoplasmic foci. This staining pattern persists in the germline up to the ∼100-cell stage, until the P4 germ cell divides to give rise to the Z2/Z3 primordial germ cells and embryonic transcription is activated in this lineage. In the ncl-1 mutant, which is characterized by increased transcription of rDNA, DAO-5-labeled nucleoli are already present at the 2-cell stage. Our results suggest a link between the activation of transcription and the initial formation of nucleoli in the C. elegans embryo

New Assembly, Reannotation and Analysis of the Entamoeba histolytica Genome Reveal New Genomic Features and Protein Content Information

Entamoeba histolytica is an anaerobic parasitic protozoan that causes amoebic dysentery. The parasites colonize the large intestine, but under some circumstances may invade the intestinal mucosa, enter the bloodstream and lead to the formation of abscesses such amoebic liver abscesses. The draft genome of E. histolytica, published in 2005, provided the scientific community with the first comprehensive view of the gene set for this parasite and important tools for elucidating the genetic basis of Entamoeba pathogenicity. Because complete genetic knowledge is critical for drug discovery and potential vaccine development for amoebiases, we have re-examined the original draft genome for E. histolytica. We have corrected the sequence assembly, improved the gene predictions and refreshed the functional gene assignments. As a result, this effort has led to a more accurate gene annotation, and the discovery of novel features, such as the presence of genome segmental duplications and the close association of some gene families with transposable elements. We believe that continuing efforts to improve genomic data will undoubtedly help to identify and characterize potential targets for amoebiasis control, as well as to contribute to a better understanding of genome evolution and pathogenesis for this parasite

Ribosomal RNA of Hyacinthus orientalis L. female gametophyte cells before and after fertilization

The nucleolar activity of Hyacinthus orientalis L. embryo sac cells was investigated. The distributions of nascent pre-rRNA (ITS1), 26S rRNA and of the 5S rRNA and U3 snoRNA were determined using fluorescence in situ hybridization (FISH). Our results indicated the different rRNA metabolism of the H. orientalis female gametophyte cells before and after fertilization. In the target cells for the male gamete, i.e., the egg cell and the central cell whose activity is silenced in the mature embryo sac (Pięciński et al. in Sex Plant Reprod 21:247–257, 2008; Niedojadło et al. in Planta doi:10.1007/s00425-012-1599-9, 2011), rRNA metabolism is directed at the accumulation of rRNPs in the cytoplasm and immature transcripts in the nucleolus. In both cells, fertilization initiates the maturation of the maternal pre-rRNA and the expression of zygotic rDNA. The resumption of rRNA transcription observed in the hyacinth zygote indicates that in plants, there is a different mechanism for the regulation of RNA Pol I activity than in animals. In synergids and antipodal cells, which have somatic functions, the nucleolar activity is correlated with the metabolic activity of these cells and changes in successive stages of embryo sac development

Experimental induction of prenucleolar bodies (PNBs) in interphase cells: interphase PNBs show similar characteristics as those typically observed at telophase of mitosis in untreated cells.

Recently, it was shown that a short exposure of living mammalian cells to low ionic strength buffers (hypotonic shock) caused partial or almost complete unraveling of interphase nucleoli. However, when the cells were released from the hypotonic shock and transferred to normal isotonic medium, functionally active and structurally integral nucleoli were reassembled at their initial positions within interphase nuclei. Here, we show further that this process is accompanied by the appearance of numerous discrete extranucleolar bodies, which have striking similarities to the prenucleolar bodies (PNBs) observed in untreated cells at telophase of mitosis. (1) Like PNBs at mitosis, hypotonically induced interphase PNBs are composed of RNA-positive granules and fibrils, contain the major nucleolar protein B23 and silver-binding proteins, but lack DNA and RNA polymerase I transcription factor UBF. (2) As for mitotic PNBs, disappearance of the interphase PNB counterparts coincides with the increase in size of reconstructed nucleoli. (3) Addition of actinomycin D does not prevent assembly of interphase PNBs, but does arrest their coalescence with the chromosomal nucleolus-organizing regions and blocks the complete reformation of nucleoli. It is concluded that the assembly of PNBs generally observed at telophase of mitosis can be induced experimentally in nuclei of interphase mammalian cells in vivo. At interphase, this process is probably initiated by changes in the intracellular ionic environment