Drosophila melanogaster is a proven model system for many aspects of human biology. Here we present a two-hybrid–based protein-interaction map of the fly proteome. A total of 10,623 predicted transcripts were isolated and screened against standard and normalized complementary DNA libraries to produce a draft map of 7048 proteins and 20,405 interactions. A computational method of rating two-hybrid interaction confidence was developed to refine this draft map to a higher confidence map of 4679 proteins and 4780 interactions. Statistical modeling of the network showed two levels of organization: a short-range organization, presumably corresponding to multiprotein complexes, and a more global organization, presumably corresponding to intercomplex connections. The network recapitulated known pathways, extended pathways, and uncovered previously unknown pathway components. This map serves as a starting point for a systems biology modeling of multicellular organisms, including humans.

Matrix attachment regions (MARs) are DNA sequences that bind an internal nuclear network of nonhistone proteins called the nuclear matrix. Thus, they may define discrete gene-containing chromatin loops in vivo. We have studied the effects of flanking transgenes with MARs on transgene expression levels in maize callus and in transformed maize plants. Three MAR elements, two from maize (Adh1 5' MAR and Mha1 5' MAR) and one from yeast (ARS1), had very different effects on transgene expression that bore no relation to their affinity for the nuclear matrix in vitro. In callus, two of the MAR elements (Adh1 5' MAR and ARS1) reduced transgene silencing but had no effect on the variability of expression. In transgenic plants, Adh1 5' MAR had the effect of localizing P-glucuronidase expression to lateral root initiation sites. A possible model accounting for the function of Adh1 5' MAR is discussed.

Human and mouse liver microsomes and membranes isolated from Escherichia coli, which expressed cytochrome P450 (CYP) 1A2, 3A4, 2C9 or 2D6, were used to investigate CYP-mediated metabolism of five selected dietary flavonoids. In human and mouse liver microsomes kaempferol, apigenin and naringenin were hydroxylated at the 3'-position to yield their corresponding analogs quercetin, luteolin and eriodictyol, whereas hesperetin and tamarixetin were demethylated at the 4'-position to yield eriodictyol and quercetin, respectively. Microsomal flavonoid metabolism was potently inhibited by the CYP1A2 inhibitors, fluvoxamine and -naphthoflavone. Recombinant CYP1A2 was capable of metabolizing all five investigated flavonoids. CYP3A4 recombinant protein did not catalyze hesperetin demethylation, but showed similar metabolic profiles for the remaining compounds, as did human microsomes and recombinant CYP1A2, although the reaction rates in general were lower as compared to CYP1A2. CYP2C9 catalyzed the 4'-demethylation of tamarixetin, whereas CYP2D6 did not seem to play any role in the metabolism of the selected flavonoids. The major involvement in flavonoid metabolism of human CYP1A2, which mediates the formation of metabolites with different biochemical properties as compared to the parent compound and furthermore is known to be expressed very differently among individuals, raises the important question of whether individual differences in the CYP enzyme activity might affect the beneficial outcome of dietary flavonoids, rendering some individuals more or less refractory to the health-promoting potential of dietary flavonoids.

The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, genistein and equol was investigated in immature female mice. Genistein and equol, administered by gavage for 4 consecutive days [post-natal day (PND) 17–20, 100 mg/kg body weight], was found to significantly increase uterine weights and the overall uterine concentration of estrogen receptor alpha (ERα). In kaempferol- and equol-exposed mice the cytosolic ERα concentration was significantly increased as compared to the solvent control, which is speculated to result in an increased sensitivity of the uterus to subsequently encountered estrogens. Oral administration of equol, genistein, biochanin A and daidzein to 6-week-old female mice revealed a great variation in their systemic bioavailability. The urinary recovery of equol was thus over 90% of a single gavage administered dose, whereas the urinary recoveries of biochanin A, genistein and daidzein were 16, 11 and 3%, respectively. Most of the metabolites were either hydroxylated or dehydrogenated forms of the parent compounds. The in vitro estrogenic potency of some of the metabolites was greater than that of the parent compounds, whereas others were of similar or lower potency. Bioavailability, metabolism, the ability to alter ERα distribution in the uterus and the estrogenic potential of parent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids.

Transposable elements are ubiquitous in plant genomes, where they frequently comprise the majority of genomic DNA, The maize genome, which is believed to be structurally representative of large plant genomes, contains single genes or small gene islands interspersed with much longer blocks of retrotransposons. Given this organization, it would be desirable to identify molecular markers preferentially located in genic regions. In this report, the features of a newly described family of miniature inverted repeat transposable elements (MITEs) (called Heartbreaker), including high copy number and polymorphism, stability, and preference for genic regions, have been exploited in the development of a class of molecular markers for maize. To this end, a modification of the AFLP procedure called transposon display was used to generate and display hundreds of genomic fragments anchored in Hbr elements. An average of 52 markers were amplified for each primer combination tested. In all, 213 polymorphic fragments were reliably scored and mapped in 100 recombinant inbred lines derived from a cross between the maize inbreds B73 x Mo17. In this mapping population, Hbr markers are distributed evenly across the 10 maize chromosomes. This procedure should be of general use in the development of markers for other MITE families in maize and in other plant and animal species where MITEs have been identified.

The momentum and angular distributions of punchthrough muons have been measured after a 10 λ calorimeter using an iron toroid magnet with 1.5 T as spectrometer. The calorimeter was inside a variable magnetic field of 0 to 3 T. The incident momentum of the π− beam ranged from 20 to 300 GeV/c. Measurements were also done at some beam momenta for π+, K+ and p. The results are compared with Monte Carlo predictions. A parameterization for the momentum spectrum of punchthrough muons was derived from the data.

Institute of Toxicology, Division of Biochemical and Genetic Toxicology, National Food Agency, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark. Correspondence to: C Brouwer. Fax: (+45) 3966 0100.

Una de las complicaciones metabólicas que se asocia con relativa frecuencia con la nutrición parenteral es la hipertrigliceridemia. Su etiología se relaciona con la alteración del aclaramiento plasmático de los lípidos, bien por una disminución de la actividad de la lipoproteinlipasa, bien por un aporte excesivo. Durante la utilización de la nutrición parenteral es importante conocer el umbral de triglicéridos plasmáticos a partir del cual la administración de lípidos exógenos es ineficiente desde el punto de vista metabólico o está asociado a sobrecarga grasa. Hay diversas situaciones clínicas como la sepsis, la insuficiencia renal, la pancreatitis, así como determinados fármacos, como glucocorticoides o ciclosporina, que se asocian con hipertrigliceridemia. En estos casos, cuando se instaura una pauta de nutrición parenteral, el riesgo de desarrollar hipertrigliceridemia es especialmente elevado. En el presente trabajo se revisan las distintas causas que pueden relacionarse con hipertrigliceridemia y que pueden suponer un factor de riesgo en pacientes con nutrición parenteral.Hypertriglyceridemia is a metabolic disorder frequently correlated with the use of parenteral nutrition. The etiology of hypertriglyceridemia in patients undergoing parenteral nutrition is associated with alterations in plasma lipid clearance due to an excessive supply or to a decrease in lipoprotein lipase activity. During parenteral nutrition therapy, it is important to determine the threshold plasma triglyceride level above which exogenous lipids cannot be efficiently metabolized or would be associated with lipid overload. Several clinical and metabolic situations have been related to hypertriglyceridemia, such as sepsis, renal failure, pancreatitis and the use of certain drugs such as glucocorticoids and cyclosporine. In these cases, parenteral nutrition increases the risk of developing hypertriglyceridemia. In the present article, we review some of the risk factors for hypertriglyceridemia in patients with parenteral nutrition.

The total punchthrough probability of showers produced by negative pions, positive pions, positive kaons and protons, has been measured as a function of depth in an absorber in a magnetic field ranging from 0 to 3 Tesla.The incident particle momentum varied from 10 to 300 GeV/c.The lateral shower development and particle multiplicity at several absorber depths have been determined.The measurements are compared with the predictions of Monte Carlo simulation programs.

The experiments at the planned 14 TeV proton-proton collider LHC will need a good identification and measurement of muons with energies of up to about 800 GeV. The production of electromagnetic secondaries by muons of energy from 10 to 300 GeV has been measured at the RD5 experiment at CERN using various detector types proposed for LHC experiments. It is demonstrated that the detectors can recognize the presence of individual hits from em secondaries, and that the muon measurement would be seriously compromised if these hits are not suppressed.

This paper gives an overview of all honeycomb strip chambers constructed so far. The method of construction is described, and results from a beam test and cosmic rays are presented.

The total punchthrough probability of showers produced by negatively charged pions of momenta 30, 40, 50, 75, 100, 200 and 300 GeV/c, has been measured in the RD5 experiment at CERN using a toroidal spectrometer. The range of the measurement extends to 5.3 m of equivalent iron. Our results have been obtained by two different analysis methods and are compared with the resutls of a previous experiment.