Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase that participates in numerous signalling pathways involved in diverse physiological processes. Several of these pathways are implicated in disease pathogenesis, which has prompted efforts to develop GSK3-specific inhibitors for therapeutic applications. However, before now, there has been no strong rationale for targeting GSK3 in malignancies. Here we report pharmacological, physiological and genetic studies that demonstrate an oncogenic requirement for GSK3 in the maintenance of a specific subtype of poor prognosis human leukaemia, genetically defined by mutations of the MLL proto-oncogene. In contrast to its previously characterized roles in suppression of neoplasia-associated signalling pathways, GSK3 paradoxically supports MLL leukaemia cell proliferation and transformation by a mechanism that ultimately involves destabilization of the cyclin-dependent kinase inhibitor p27(Kip1). Inhibition of GSK3 in a preclinical murine model of MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a candidate cancer drug target.     

Spatial organization of northern flying squirrels, Glaucomys sabrinus: territoriality in females?

We determined home-range overlap among northern flying squirrels ( Glaucomys sabrinus ) to assess their spatial organization. We found extensive home-range overlap among females, and though this overlap could reflect social behavior, we found no evidence of attraction among females, with only one instance of den-sharing. Instead, our results suggest that females share foraging areas but may be territorial in portions of the home range, especially around den trees and during young-rearing. Home-range overlap could also result from the extrinsic effect of forest fragmentation due to timber harvest, which might impede dispersal and force squirrels to cluster on remaining fragments of suitable habitat. Determinamos el sobrelapamiento del rango hogareño entre las ardillas voladoras del norte ( Glaucomys sabrinus ) para evaluar su organización espacial. Encontramos un extenso sobrelapamientos en los rangos hogareños entre las hembras; aunque esto podría reflejar su comportamiento social, no encontramos evidencia de atracción entre hembras, y en sólo un caso compartieron su guarida. Vienen su lugar, nuestros resultados sugieren que las hembras comparten áreas de forrajeo pero pueden ser territoriales en ciertas partes de su rango hogareño, particularmente cerca de los árboles donde tienen guaridas y cuando tienen cría. El sobrelapamiento del rango hogareño también podría ser el resultado del efecto extrínseco de la fragmentación forestal debido a la tala de madera, el cual podría impedir la dispersión y forzar a las ardillas a agruparse en fragmentos de hábitat adecuado que queden.     

Genetic differentiation of rare and common varieties of Eriogonum shockleyi (Polygonaceae) in Idaho using ISSR variability

Idaho populations of Eriogonum shockleyi are divided taxonomically into 2 varieties: E. shockleyi var. packardae , which is endemic to Idaho, and the typical variety, which is widespread in the western United States. Recent morphological investigations of E. shockleyi in Idaho have identified potentially reliable morphological characters for field identification of the subspecific taxa. This paper investigates the genetic basis for the separation of the 2 varieties of E. shockleyi using inter simple-sequence repeats (ISSR) markers. Although we found some morphological differences between the populations that correlated with the 2 varieties, we identified no molecular markers in this study to distinguish between them. Morphological measurements obtained in the field indicate that although a population may have an overall average morphology that defines the variety, some individuals in nearly all populations have putative diagnostic characters that define the other variety. The morphological characters used to distinguish the 2 varieties are most likely the result of environmental variability and could result from differences in precipitation and soil water retention. Alternatively, high levels of outcrossing through pollen flow could be obscuring selection for morphological characters at particular sites.     

Arbuscular mycorrhizae of Mojave Desert plants

Roots of 15 Mojave Desert plant species were assessed for arbuscular mycorrhizal (AM) colonization in spring and autumn 1999. Another 19 species were assessed in autumn only. Perennial species were AM colonized, whereas annual species contained very low levels of AM hyphae or were nonmycorrhizal. The nonnative tree Tamarix ramosissima was also nonmycorrhizal. Levels of hyphae changed over the season in 2 species, arbuscle levels increased in 1 species, and vesicles decreased in 7 species. Mycorrhizal inoculum potential (MIP) was assessed in the soils associated with spring-collected plants. All soils were found to contain MIP. MIP values were not correlated with AM root colonization.     

Breeding range expansion of the Starling in Utah

The discovery and observation of colonies of starlings nesting in the eastern Great Basin desert indicates further expansion of the breeding range of this species in Utah. Data on nest site selection, nesting productivity, food habits, and relationships with other avian species are presented.     

Sexual imprinting of a Barn Owl ( Tyto alba ) on humans

The sexual imprinting of a Barn Owl ( Tyto alba ) on humans is reported.     

New variety of Mentzelia multicaulis (Loasaceae) from the Book Cliffs of Utah

Described is Mentzelia multicaulis (Osterh.) Goodman var. librina Thorne & F. J. Smith.     

The identity of Bocourt's lizard Eumeces capito 1879

Eumeces capito Boucourt, 1879, is a senior synonym of Eumeces xanthi Günther, 1889. No exception to application of the Law of Priority is recommended in this case. The type locality of E. capito as originally published (“La côte oriental des Etats - Unis”) is erroneous. Undoubtedly the correct locality is China, but it is not restricted at present.         

Interaction of DISC1 with the PTB domain of Tensin2

The gene for Disrupted-in-Schizophrenia 1 (DISC1) is amongst the most significant risk genes for schizophrenia. The DISC1 protein is an intracellular scaffolding molecule thought to act an important hub for protein interactions involved in signalling for neural cell differentiation and function. Tensin2 is an intracellular actin-binding protein that bridges the intracellular portion of transmembrane receptors to the cytoskeleton, thereby regulating signalling for cell shape and motility. In this study, we probed in molecular detail a novel interaction between DISC1 and Tensin2. Western blot and confocal microscopic analyses revealed widespread expression of both DISC1 and Tensin2 proteins throughout the mouse brain. Furthermore, we have developed novel anti-DISC1 antibodies that verified the predominant expression of a 105-kDa isoform of DISC1 in the rodent brain as well as in human cells. In the mouse brain, both proteins showed region-specific expression patterns, including strong expression in the pyramidal cell layer of the hippocampus and dentate gyrus. DISC1–Tensin2 colocalisation was most clearly observed in the Purkinje cells of the mouse cerebellum. Biochemical coimmunoprecipitation experiments revealed an interaction between endogenous DISC1 and Tensin2 proteins in the mouse brain. Further pulldown studies in human cells using Myc-tagged Tensin2 constructs revealed that DISC1 specifically interacts with the C-terminal PTB domain of Tensin2 in a phosphorylation-independent manner. This new knowledge on the DISC1–Tensin2 interaction, as part of the wider DISC1 interactome, should further elucidate the signalling pathways that are perturbed in schizophrenia and other mental disorders.