FRA10B structure reveals common elements in repeat expansion and chromosomal fragile site genesis

A common mechanism for chromosomal fragile site genesis is not yet apparent. Folate-sensitive fragile sites are expanded p(CCG)n repeats that arise from longer normal alleles. Distamycin A or bromodeoxyuridine-inducible fragile site FRA16B is an expanded AT-rich similar to 33 bp repeat; however, the relationship between normal and fragile site alleles is not known. Here, we report that bromodeoxyuridine-inducible, distamycin A-insensitive fragile site FRA10B is composed of expanded similar to 42 bp repeats. Differences in repeat motif length or composition between different FRA10B families indicate multiple independent expansion events. Some FRA10B alleles comprise a mixture of different expanded repeat motifs. FRA10B fragile site and long normal alleles share flanking polymorphisms. Somatic and intergenerational FRA10B repeat instability analogous to that found in expanded trinucleotide repeats supports dynamic mutation as a common mechanism for repeat expansion.

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice

Previously we described activating mutations of h beta(c), the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, h beta(c)FI Delta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the h beta(c)FI Delta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in h beta(c) may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic h beta(c) activation has the potential to contribute to pathological events in the central nervous system.

The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and Hop is located in the dimerization domain of hsp90

Structurally related tetratricopeptide repeat motifs in steroid receptor-associated immunophilins and the STI1 homolog, Hop, mediate the interaction with a common cellular target, hsp90, We have identified the binding domain in hsp90 for cyclophilin 40 (CyP40) using a two-hybrid system screen of a mouse cDNA library. All isolated clones encoded the intact carboxyl terminus of hsp90 and overlapped with a common region corresponding to amino acids 558-724 of murine hsp84, The interaction was confirmed in vitro with bacterially expressed CyP40 and deletion mutants of hsp90 beta and was delineated further to a 124-residue COOH-terminal segment of hsp90, Deletion of the conserved MEEVD sequence at the extreme carboxyl terminus of hsp90 precludes interaction with CyP40, signifying an important role for this motif in hsp90 function. We show that CyP40 and Hop display similar interaction profiles with hsp90 truncation mutants and present evidence for the direct competition of Hop and FK506-binding protein 52 with CyP40 for binding to the hsp90 COOH-terminal region. Our results are consistent with a common tetratricopeptide repeat interaction site for Hop and steroid receptor associated immunophilins within a discrete COOH-terminal domain of hsp90. This region of hsp90 mediates ATP-independent chaperone activity, overlaps the hsp90 dimerization domain, and includes structural elements important for steroid receptor interaction.

Quantum oscillations in quasi-one-dimensional metals with spin-density-wave ground states

We consider the magnetoresistance oscillation phenomena in the Bechgaard salts (TMTSF)(2)X, where X = ClO4, PF6, and AsF6 in pulsed magnetic fields to 51 T. Of particular importance is the observation of a new magnetoresistance oscillation for X = ClO4 in its quenched state. In the absence of any Fermi-surface reconstruction due to anion order at low temperatures, all three materials exhibit nonmonotonic temperature dependence of the oscillation amplitude in the spin-density-wave (SDW) state. We discuss a model where, below a characteristic temperature T* within the SDW state, a magnetic breakdown gap opens. [S0163-1829(99)00904-2].

Architecture and morphogenesis of grain sorghum, Sorghum bicolor (L.) Moench

Plant architecture has been neglected in most studies of biomass allocation in crops. To help redress this situation for grain sorghum (Sorghum bicolor (L.) Moench), we used a 3D digitiser to measure the dimensions and orientations of vegetative and reproductive structures and derived thermal time-based functions for architectural changes during morphogenesis. Our plants, which were grown in a greenhouse, controlled environment cabinets and the field, covered a large, three-fold, size range when mature. This allowed us to detect some general architectural relationships and to fit morphogenetic functions common across the size range we observed. For example, the relationship between the lengths of successive fully-expanded leaves within a plant was nearly constant for all plants. The lengths of existing leaf blades were accurate predictors of the lengths of up to six subsequently-formed blades in our plants. Similar constant relationships were detected for internode lengths in the panicle and for heights above ground of the collars of successive leaves, even though these traits varied a lot between growth conditions. We suggest that such architectural relationships may be used to link the effect of previous growth conditions to future growth potential, and in that way to predict future partitioning. Our results provide the basis for a preliminary model of sorghum morphogenesis which could eventually become useful in conjunction with crop models by allowing resource acquisition to be related to changes in plant architecture during development. (C) 1999 Elsevier Science B.V. All rights reserved.

A cell type-specific constitutive point mutant of the common beta-subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors requires the GM-CSF receptor alpha-subunit for activation

The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific alpha-subunit (hGMR alpha) and a common signal-transducing beta-subunit (hpc) that is shared with the interleukin-3 and -5 receptors, We have previously identified a constitutively active extracellular point mutant of hpc, I374N, that can confer factor independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B. J., D'Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276-4287), This restricted activity suggested the involvement of cell type-specific signaling molecules in the activation of this mutant. We report here that one such molecule is the mouse GMR alpha (mGMR alpha) subunit, since introduction of mGMR alpha, but not hGMR alpha, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred factor independence, Experiments utilizing mouse/human chimeric GMR alpha subunits indicated that the species specificity lies in the extracellular domain of GMRa. Importantly, the requirement for mGMR alpha correlated with the ability of I374N (but not wild-type hpc) to constitutively associate with mGMRa. Expression of I374N in human factor-dependent UT7 cells also led to factor-independent proliferation, with concomitant up-regulation of hGMR alpha surface expression. Taken together, these findings suggest a critical role for association with GMR alpha in the constitutive activity of I374N.

Sedimentologic, petrographic, and sulfur isotope constraints on fine-grained pyrite formation at Mount Isa Mine and environs, Northwest Queensland, Australia

Fine-grained pyrite is the earliest generation of pyrite and the most abundant sulfide within the Urquhart Shale at Mount Isa, northwest Queensland. The pyrite is intimately interbanded with ore-grade Pb-Zn miner alization at the Mount Isa mine but is also abundant north and south of the mine at several stratigraphic horizons within the Urquhart Shale. Detailed sedimentologic, petrographic, and sulfur isotope studies of the Urquhart Shale, mostly north of the mine, reveal that the fine-grained pyrite (delta(34)S = -3.3 to +26.3 parts per thousand) formed by thermochemical sulfate reduction during diagenesis. The sulfate source was local sulfate evaporites, pseudo morphs of which are present throughout the Urquhart Shale (i.e., gypsum, anhydrite, and barite). Deep-burial diagenetic replacement of these evaporites resulted in sulfate-bearing ground waters which migrated parallel to bedding. Fine-grained pyrite formed where these fluids infiltrated and then interacted with carbon-rich laminated siltstones. Comparison of the sulfur isotope systematics of fine-grained pyrite and spatially associated base metal sulfides from the Mount Isa Pb-Zn and Cu orebodies indicates a common sulfur source of ultimately marine origin for all sulfide types. Different sulfur isotope ratio distributions for the various sulfides are the result of contrasting formation mechanisms and/or depositional conditions rather than differing sulfur sources. The sulfur isotope systematics of the base metal and associated iron sulfide generations are consistent with mineralization by reduced hydrothermal fluids, perhaps generated by bulk reduction of evaporite-sourced sulfate-bearing waters generated deeper in the Mount Isa Group, the sedimentary sequence which contains the Urquhart Shale. The available sulfur isotope data from the Mount Isa orebodies are consistent with either a chemically and thermally zoned, evolving Cu-Pb-Zn system, or discrete Cu and Pb-Zn mineralizing events linked by a common sulfur source.

Myeloproliferative disorder and leukaemia in mice induced by different classes of constitutive mutants of the human IL-3/IL-5/GM-CSF receptor common beta subunit

Several constitutively active mutant forms of the common β subunit of the human IL-3, IL-5 and GM-CSF receptors (hβc), which enable it to signal in the absence of ligand, have recently been described. Two of these, V449E and I374N, are amino acid substitutions in the transmembrane and extracellular regions of hβc, respectively. A third, FIΔ, contains a 37 amino acid duplication in the extracellular domain. We have shown previously that when expressed in primary murine haemopoietic cells, the extracellular mutants confer factor-independence on cells of the neutrophil and monocyte lineages only, whereas V449E does so on all cell types of the myeloid and erythroid compartments. To study the in vivo effects and leukaemic potential of these mutants, we have expressed all three in mice by bone marrow reconstitution using retrovirally infected donor cells. Expression of the extracellular mutants leads to an early onset, chronic myeloproliferative disorder marked by elevations in the neutrophil, monocyte, erythrocyte and platelet lineages. In contrast, expression of V449E leads to an acute leukaemia-like syndrome of anaemia, thrombocytopaenia and blast cell expansion. These data support the possibility that activating mutations in hβc are involved in haemopoietic disorders in man.

Subgroup relations: A comparison of mutual intergroup differentiation and common ingroup identity models of prejudice reduction

Two studies examined relations between groups (humanities and math-science students) that implicitly or explicitly share a common superordinate category (university student). In Experiment 1, 178 participants performed a noninteractive decision-making task during which category salience was manipulated in a 2 (superordinate category salience) x 2 (subordinate category salience) between-groups design. Consistent with the mutual intergroup differentiation model, participants for whom both categories were salient exhibited the lowest levels of bias, whereas bias was strongest when the superordinate category alone was made salient. This pattern of results was replicated in Experiment 2 (N = 135). In addition, Experiment 2 demonstrated that members of subgroups that are nested within a superordinate category are more sensitive to how the superordinate category is represented than are members of subgroups that extend beyond the boundaries of the superordinate category.

Determining forest structural attributes using an inverted geometric-optical model in mixed eucalypt forests, Southeast Queensland, Australia

The Montreal Process indicators are intended to provide a common framework for assessing and reviewing progress toward sustainable forest management. The potential of a combined geometrical-optical/spectral mixture analysis model was assessed for mapping the Montreal Process age class and successional age indicators at a regional scale using Landsat Thematic data. The project location is an area of eucalyptus forest in Emu Creek State Forest, Southeast Queensland, Australia. A quantitative model relating the spectral reflectance of a forest to the illumination geometry, slope, and aspect of the terrain surface and the size, shape, and density, and canopy size. Inversion of this model necessitated the use of spectral mixture analysis to recover subpixel information on the fractional extent of ground scene elements (such as sunlit canopy, shaded canopy, sunlit background, and shaded background). Results obtained fron a sensitivity analysis allowed improved allocation of resources to maximize the predictive accuracy of the model. It was found that modeled estimates of crown cover projection, canopy size, and tree densities had significant agreement with field and air photo-interpreted estimates. However, the accuracy of the successional stage classification was limited. The results obtained highlight the potential for future integration of high and moderate spatial resolution-imaging sensors for monitoring forest structure and condition. (C) Elsevier Science Inc., 2000.