Conserved IKAROS-regulated genes associated with B-progenitor acute lymphoblastic leukemia outcome

Genetic alterations disrupting the transcription factor IKZF1 (encoding IKAROS) are associated with poor outcome in B lineage acute lymphoblastic leukemia (B-ALL) and occur in >70% of the high-risk BCR-ABL1+ (Ph+) and Ph-like disease subtypes. To examine IKAROS function in this context, we have developed novel mouse models allowing reversible RNAi-based control of Ikaros expression in established B-ALL in vivo. Notably, leukemias driven by combined BCR-ABL1 expression and Ikaros suppression rapidly regress when endogenous Ikaros is restored, causing sustained disease remission or ablation. Comparison of transcriptional profiles accompanying dynamic Ikaros perturbation in murine B-ALL in vivo with two independent human B-ALL cohorts identified nine evolutionarily conserved IKAROS-repressed genes. Notably, high expression of six of these genes is associated with inferior event-free survival in both patient cohorts. Among them are EMP1, which was recently implicated in B-ALL proliferation and prednisolone resistance, and the novel target CTNND1, encoding P120-catenin. We demonstrate that elevated Ctnnd1 expression contributes to maintenance of murine B-ALL cells with compromised Ikaros function. These results suggest that IKZF1 alterations in B-ALL leads to induction of multiple genes associated with proliferation and treatment resistance, identifying potential new therapeutic targets for high-risk disease

Kleptoparasitism in gulls Laridae at an urban and a coastal foraging environment: an assessment of ecological predictors

Capsule: Kleptoparasitism in gulls occurred at a greater rate at an urban compared with a coastal site. Population density and prey size predicted the rate of kleptoparasitism at the urban site. Aims: To investigate and assess the ecological variables associated with kleptoparasitism among gulls at urban and rural sites. Methods: Field observations were conducted at Brancaster (coastal rural) and Billingsgate Market (urban) to examine differences in the rate of kleptoparasitism in mixed-species flocks of gulls. Four key variables (prey size, population density, season and species) were assessed as predictors of kleptoparasitism. Results: Generalized linear models revealed significant effects on kleptoparasitism rate of site, population density and prey size, and two-way interactions between these main terms. Population density and prey size differed significantly between sites, but population density appeared to predict the rate of kleptoparasitism. Conclusion: Kleptoparasitism may well aid invasion and increase the range of environments a gull can tolerate by helping them meet their energy needs in novel environments where normal foraging behaviours are difficult to implement

An early Permian brachiopod–gastropod fauna from the Calytrix Formation, Barbwire Terrace, Canning Basin, Western Australia

A small brachiopod–gastropod fauna from a core close to the base of the Calytrix Formation within the Grant Group includes the brachiopods Altiplecus decipiens (Hosking), Myodelthyrium dickinsi (Thomas), Brachythyrinella narsarhensis (Reed), Neochonetes (Sommeriella) obrieni Archbold, Tivertonia barbwirensis sp. nov. and the gastropod Peruvispira canningensis sp. nov. The fauna has affinities with that of the late Sakmarian‒early Artinskian Nura Nura Member directly overlying the Grant Group in other parts of the basin but, as with all lower Cisuralian (and Pennsylvanian) glacial strata in Western Australia, its precise age remains poorly constrained, especially in terms of correlation to international stages. Although the Calytrix fauna lies within the Pseudoreticulatispora confluens Palynozone, the only real constraint on its age (and that of the associated glacially influenced strata) is from Sakmarian (Sterlitamakian) and stratigraphically younger faunas. A brief review of radiometric ages from correlative strata elsewhere in Gondwana shows that those ages need to be updated. The presence of Asselian strata and the position of the Carboniferous‒Permian boundary remain unclear in Western Australia.Arturo César Taboada [[email protected]], CONICET-Laboratorio de Investigaciones en Evolución y Biodiversidad (LIEB), Facultad de Ciencias Naturales, Sede Esquel, Universidad Nacional de la Patagonia ‘San Juan Bosco’, Edificio de Aulas, Ruta Nacional 259, km. 16,5, Esquel U9200, Chubut, Argentina; Arthur Mory [[email protected]], Geological Survey of Western Australia, 100 Plain Street, East Perth, WA 6004, School of Earth and Environment, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; Guang R. Shi [[email protected]], School of Life and Environmental Sciences, Deakin University, Melbourne Burwood Campus, 221 Burwood Highway, Burwood, Victoria 3125, Australia; David W. Haig [[email protected]], School of Earth and Environment (M004), The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia; María Karina Pinilla [[email protected]], División Paleozoología Invertebrados, Museo de Ciencias Naturales de La Plata, Paseo del Bosque s/n, 1900 La Plata, Buenos Aires, Argentina