Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion

The emergence of complex patterns of organization close to the Cambrian boundary is known to have happened over a (geologically) short period of time. It involved the rapid diversification of body plans and stands as one of the major transitions in evolution. How it took place is a controversial issue. Here we explore this problem by considering a simple model of pattern formation in multicellular organisms. By modeling gene network-based morphogenesis and its evolution through adaptive walks, we explore the question of how combinatorial explosions might have been actually involved in the Cambrian event. Here we show that a small amount of genetic complexity including both gene regulation and cell-cell signaling allows one to generate an extraordinary repertoire of stable spatial patterns of gene expression compatible with observed anteroposterior patterns in early development of metazoans. The consequences for the understanding of the tempo and mode of the Cambrian event are outlined.Comment: to appear in International Journal of Developmental Biology, special issue on Evo-Devo (2003

ATP-dependent DNA ligases

By catalyzing the joining of breaks in the phosphodiester backbone of duplex DNA, DNA ligases play a vital role in the diverse processes of DNA replication, recombination and repair. Three related classes of ATP-dependent DNA ligase are readily apparent in eukaryotic cells. Enzymes of each class comprise catalytic and non-catalytic domains together with additional domains of varying function. DNA ligase I is required for the ligation of Okazaki fragments during lagging-strand DNA synthesis, as well as for several DNA-repair pathways; these functions are mediated, at least in part, by interactions between DNA ligase I and the sliding-clamp protein PCNA. DNA ligase III, which is unique to vertebrates, functions both in the nucleus and in mitochondria. Two distinct isoforms of this enzyme, differing in their carboxy-terminal sequences, are produced by alternative splicing: DNA ligase IIIα has a carboxy-terminal BRCT domain that interacts with the mammalian DNA-repair factor XrccI, but both α and β isoforms have an amino-terminal zinc-finger motif that appears to play a role in the recognition of DNA secondary structures that resemble intermediates in DNA metabolism. DNA ligase IV is required for DNA non-homologous end joining pathways, including recombination of the V(D)J immunoglobulin gene segments in cells of the mammalian immune system. DNA ligase IV forms a tight complex with Xrcc4 through an interaction motif located between a pair of carboxy-terminal BRCT domains in the ligase. Recent structural studies have shed light on the catalytic function of DNA ligases, as well as illuminating protein-protein interactions involving DNA ligases IIIα and IV

Self-Maintained Coherent Oscillations in Dense Neutrino Gases

We present analytical solutions to the nonlinear equations describing the behavior of a gas of neutrinos with two flavors. Self-maintained coherent flavor oscillations are shown to occur when the gas density exceeds a critical value determined by the neutrino masses and the mean neutrino energy in the gas. Similar oscillations may have occurred in the early Universe.Comment: To appear in Physical Review D, July 199

Digital poverty in Margate: a study of two hyperlocal communities

This report presents the findings of an in-depth, qualitative study of digital poverty from the perspectives of two hyperlocal communities in the UK seaside town of Margate. Specifically, the study examines members of Margate’s Roma community and its Creative Diaspora, drawing from interviews with individuals from these communities, in order to better understand specific lived experiences of digital poverty within the changing context of Margate as a place. The analysis is presented under three key headings: skills, productivity, and infrastructure.The British Academ

Bimodal Coherence in Dense Self-Interacting Neutrino Gases

Analytical solutions are obtained to the nonlinear equations describing neutrino oscillations when explicit neutrino-antineutrino asymmetries are present. Such a system occurs in the early Universe if neutrinos have a non-zero chemical potential. Solutions to the equations lead to a new type of coherent behavior governed by two modes. These bimodal solutions provide new insights into dense neutrino gases and into neutrino oscillations in the early Universe, thereby allowing one to surmise the flavor behavior of neutrinos with a non-zero chemical potential.Comment: 21 pages in Latex, 11 figures packaged in one Postscript file. Figures also obtainable as 20 gif files at http://www.sci.ccny.cuny.edu/~ssamuel/bimodalfigs.html Revision on 4/19/96 was to pack the figures more sensibly. This paper is to appear in a May issue of Phys. Rev.

Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans

This is the publisher's version, also available electronically from http://www.biomedcentral.com/1471-2164/14/304Background: Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds. Results: Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration. Conclusions: Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration

The brown adipocyte differentiation pathway in birds: An evolutionary road not taken

Background Thermogenic brown adipose tissue has never been described in birds or other non-mammalian vertebrates. Brown adipocytes in mammals are distinguished from the more common white fat adipocytes by having numerous small lipid droplets rather than a single large one, elevated numbers of mitochondria, and mitochondrial expression of the nuclear gene UCP1, the uncoupler of oxidative phosphorylation responsible for non-shivering thermogenesis. Results We have identified in vitro inductive conditions in which mesenchymal cells isolated from the embryonic chicken limb bud differentiate into avian brown adipocyte-like cells (ABALCs) with the morphological and many of the biochemical properties of terminally differentiated brown adipocytes. Avian, and as we show here, lizard species lack the gene for UCP1, although it is present in amphibian and fish species. While ABALCs are therefore not functional brown adipocytes, they are generated by a developmental pathway virtually identical to brown fat differentiation in mammals: both the common adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ), and a coactivator of that factor specific to brown fat differentiation in mammals, PGC1α, are elevated in expression, as are mitochondrial volume and DNA. Furthermore, ABALCs induction resulted in strong transcription from a transfected mouse UCP1 promoter. Conclusion These findings strongly suggest that the brown fat differentiation pathway evolved in a common ancestor of birds and mammals and its thermogenicity was lost in the avian lineage, with the degradation of UCP1, after it separated from the mammalian lineage. Since this event occurred no later than the saurian ancestor of birds and lizards, an implication of this is that dinosaurs had neither UCP1 nor canonically thermogenic brown fat.Nadejda V Mezentseva, Jaliya S Kumaratilake and Stuart A Newma

The Discovery of XY Sex Chromosomes in a \u3cem\u3eBoa\u3c/em\u3e and \u3cem\u3ePython\u3c/em\u3e

For over 50 years, biologists have accepted that all extant snakes share the same ZW sex chromosomes derived from a common ancestor [1, 2, 3], with different species exhibiting sex chromosomes at varying stages of differentiation. Accordingly, snakes have been a well-studied model for sex chromosome evolution in animals [1, 4]. A review of the literature, however, reveals no compelling support that boas and pythons possess ZW sex chromosomes [2, 5]. Furthermore, phylogenetic patterns of facultative parthenogenesis in snakes and a sex-linked color mutation in the ball python (Python regius) are best explained by boas and pythons possessing an XY sex chromosome system [6, 7]. Here we demonstrate that a boa (Boa imperator) and python (Python bivittatus) indeed possess XY sex chromosomes, based on the discovery of male-specific genetic markers in both species. We use these markers, along with transcriptomic and genomic data, to identify distinct sex chromosomes in boas and pythons, demonstrating that XY systems evolved independently in each lineage. This discovery highlights the dynamic evolution of vertebrate sex chromosomes and further enhances the value of snakes as a model for studying sex chromosome evolution

Predictability of prescription drug expenditures for Medicare beneficiaries

MCBS data are used to analyze the predictability of drug expenditures by Medicare beneficiaries. Predictors include demographic characteristics and measures of health status, the majority derived using CMS\u27 diagnosis cost group/hierarchical condition category (DCG/HCC) risk-adjustment methodology. In prospective models, demographic variables explained 5 percent of the variation in drug expenditures. Adding health status measures raised this figure between 10 and 24 percent of the variation depending on the model configuration. Adding lagged drug expenditures more than doubled predictive power to 55 percent. These results are discussed in the context of forecasting, and risk adjustment for the proposed new Medicare drug benefit