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The molecular basis of advanced systemic mastocytosis (SM) is not fully understood and despite novel therapies the prognosis remains dismal. Exome sequencing of an index-patient with mast cell leukemia (MCL) uncovered biallelic loss-of-function mutations in the SETD2 histone methyltransferase gene. Copy-neutral loss-of-heterozygosity at 3p21.3 (where SETD2 maps) was subsequently found in SM patients and prompted us to undertake an in-depth analysis of SETD2 copy number, mutation status, transcript expression and methylation levels, as well as functional studies in the HMC-1 cell line and in a validation cohort of 57 additional cases with SM, including MCL, aggressive SM and indolent SM. Reduced or no SETD2 protein expression—and consequently, H3K36 trimethylation—was found in all cases and inversely correlated with disease aggressiveness. Proteasome inhibition rescued SETD2 expression and H3K36 trimethylation and resulted in marked accumulation of ubiquitinated SETD2 in SETD2-deficient patients but not in patients with near-normal SETD2 expression. Bortezomib and, to a lesser extent, AZD1775 alone or in combination with midostaurin induced apoptosis and reduced clonogenic growth of HMC-1 cells and of neoplastic mast cells from advanced SM patients. Our findings may have implications for prognostication of SM patients and for the development of improved treatment approaches in advanced SM.

Abstract:  Transgenic white poplar plants (Populus alba L.) expressing the nptII gene and the bar gene from Streptomyces hygroscopicus have been produced using Agrobacterium tumefaciens-mediated gene transfer. Eleven kanamycin-resistant plant lines were obtained with a transformation frequency of 7%. Successful genetic transformation was confirmed by Southern and northern analyses. The level of resistance to the commercial preparation of phosphinothricin (Basta; Roussel-Hoechst Agrovet) was evaluated by in vitro and in vivo assays. Using in vitro selective conditions for phosphinothricin, only plantlets from four kanamycin-resistant independent lines remained green and continued to grow and root. After transfer to the growth chamber, all selected transgenic lines were shown to be completely resistant to the herbicide Basta with doses equivalent to 6 l ha–1 (normal field dosage) and were tolerant at concentration of 12 l ha–1. This is the first report describing the genetic transformation of a P. alba clonal cultivar of commercial interest with a gene of agronomic value.

A class of soluble three "species" reaction-diffusion type systems is presented Exact solutions are obtained which show turbulent spatio-temporal evolution All homogeneous evolution tends asymptotically toward an attractor which is shown to be a two layered two dimensional manifold in the three dimensional species space. Sustained aperiodic spatio-temporal solutions are also found.

Multiple time scale arguments are used to show that near a Hopf bifurcation to a chemical oscillation the dynamics of the system reduces to that of a classic soluble limit cycle system. A birth and death master equation is then introduced and the spectrum of the resulting transition operator is shown to be complex. Exact solutions of the master equation are obtained both for the steady and (for a rather general class of systems) “excited” states. Thus a simple basis of universality of critical properties in chemical oscillations is provided.

By application of a projection operator technique we derive a formally exact generalization of the nonlinear mean field master equation introduced recently for the study of local fluctuations in a reacting medium. Our starting point is a phenomenological cell master equation. The results of our theory are applicable to the theory of a fluctuating hydrodynamic reacting system. The mean field equation is placed on a firm theoretical foundation by showing it to be the lowest order approximation in an expansion in the dimensionality of the physical space keeping the product of the number of nearest neighbors (an increasing function of dimensionality) and the typical diffusion coefficient constant. A more accurate nonlinear master equation that allows for the correlation and fluctuations in the environment of a given volume element is derived in the form of an augmented mean field equation.

The gl8 locus of maize (Zea mays L.) was previously defined by a mutation that reduces the amount and alters the composition of seedling cuticular waxes. Sixty independently derived gl8 mutant alleles were isolated from stocks that carried the Mutator transposon system. A DNA fragment that contains a Mu8 transposon and that co-segregates with one of these alleles, gl8-Mu3142, was identified and cloned. DNA flanking the Mu8 transposon was shown via allelic cross-referencing experiments to represent the gl8 locus. The gl8 probe revealed a 1.4-kb transcript present in wild-type seedling leaves and, in lesser amounts, in other organs and at other developmental stages. The amino acid sequence deduced from an apparently full-length gl8 cDNA exhibits highly significant sequence similarity to a group of enzymes from plants, eubacteria, and mammals that catalyzes the reduction of ketones. This finding suggests that the GL8 protein probably functions as a reductase during fatty acid elongation in the cuticular wax biosynthetic pathway.

We present results on the time correlation function of a system undergoing absorptive optical bistability. We first use the Zwanzig-Mori formalism to calculate time correlation functions both near marginal stability points and in the coexistence region. Near marginal stability the theory predicts large deviations from a single exponential form of the correlation function. The truncated continued fraction expansion is shown to become inapplicable close to the coexistence point. The difficulties are due to the presence of long time scales, viz. the very large mean first passage times between the two metastable steady states. When these scales are important we show that the memory kernel relaxation is no longer faster than that of a field fluctuation. An increase in the size of the system increases the disparity of the time scales and thus exacerbates the problems of the projection operator formalism as used here following reference [14].