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Summary: Network component analysis (NCA) is a method to deduce transcription factor (TF) activities and TF-gene regulation control strengths from gene expression data and a TF-gene binding connectivity network. Previously, this method could analyze a maximum number of regulators equal to the total sample size because of the identifiability limit in data decomposition. As such, the total number of source signal components was limited to the total number of experiments rather than the total number of biological regulators. However, networks that have less transcriptome data points than the number of regulators are of interest. Thus it is imperative to develop a theoretical basis that allows realistic source signal extraction based on relatively few data points. On the other hand, such methods would inherently increase numerical challenges leading to multiple solutions. Therefore, solutions to both the problems are needed. Results: We have improved NCA for transcription factor activity (TFA) estimation, based on the observation that most genes are regulated by only a few TFs. This observation leads to the derivation of a new identifiability criterion which is tested during numerical iteration that allows us to decompose data when the number of TFs is greater than the number of experiments. To show that our method works with real microarray data and has biological utility, we analyze Saccharomyces cerevisiae cell cycle microarray data (73 experiments) using a TF-gene connectivity network (96 TFs) derived from ChIP-chip binding data. We compare the results of NCA analysis with the results obtained from ChIP-chip regression methods, and we show that NCA and regression produce TFAs that are qualitatively similar, but the NCA TFAs outperform regression in statistical tests. We also show that NCA can extract subtle TFA signals that correlate with known cell cycle TF function and cell cycle phase. Overall we determined that 31 TFs have statistically periodic TFAs in one or more experiments, 75% of which are known cell cycle regulators. In addition, we find that the 12 TFAs that are periodic in two or more experiments correspond to well-known cell cycle regulators. We also investigated TFA sensitivity to the choice of connectivity network we constructed two networks using different ChIP-chip p-value cut-offs. Availability: The NCA Toolbox for MATLAB is available at http://www.seas.ucla.edu/~liaoj/download.htm Contact: liaoj@seas.ucla.edu

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

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Motivation: Gene expression arrays enable measurements of transcription values for a large number or all genes in the genome. In order to better interpret these resluts and to use them to reconstruct transcription networks, information on location of binding sites for regulatory proteins in the entire genome is needed. In particular, this represents an open problem in Escherichia coli. Results: We describe the first implementation of dictionary-style models to the study of transcription factors binding sites in an entire genome. Vocabulon's unique feature is that it can both reconstruct binding sites characterized by unknown motifs and impute locations of known binding sites in long sequences by simultaneous search. On one hand, the dictionary model specifies a probability for the entire sequence taking simultaneously into account all the possible binding sites. This greatly reduces the number of false positives. On the other hand, the possibility of refining motif description, as an increasig number of binding sites are identified, augments the sensitivity of the method. We illustrate these properties with examples in E.coli. The results of gene expression arrays are used both to guide the search and corroborate it. Availability: For copy of the Vocabulon program and other details please contact csabatti@mednet.ucla.edu Contact: csabatti@mednet.ucla.edu

For Abstract see ChemInform Abstract in Full Text.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Photolysis of the benzobicyclooctenedione (I) yields the benzobicycloheptenone (II) and the intermediate dihydronaphthalene (III) which is converted to the naphthalene (IV) and the divinylbenzene (V).

The successful conversion of (+)‐anhydroryanodol (I) into (+)‐ryanodol (III) is accomplished in two steps.

The purposes of this study were to determine the extent of absorption of lead (Pb) in mining waste soil from Butte, Montana, and to investigate the effect of mining waste soil dose (g soil/day) on tissue lead concentrations. Young, 7- to 8-week-old male and female Sprague-Dawley rats (5/sex/group) were given mining waste soil that contained 810 or 3908 ppm lead mixed in a purified diet (AIN-76) at four different dose levels (0.2, 0.5, 2, and 5% dietary soil) for 30 consecutive days. Standard groups included untreated controls and dosed feed soluble lead acetate groups (1, 10, 25, 100, and 250 μg Pb/g feed). The test soil dose levels bracketed a pica child's soil exposure level and the lead acetate concentrations bracketed the test soil dose levels of lead. Liver, blood, and femur were analyzed for total lead concentration using graphite furnace atomic absorption spectroscopy. Clinical signs, body weight, food consumption, and liver weights for test soil and standard groups were similar to control. Tissue lead concentrations from test soil animals were significantly lower than the tissue concentrations for the lead acetate group. Relative percentage bioavailability values, based on lead acetate as the standard, were independent of the two different test soils, dose levels, and sex and were only slightly dependent on the tissue (blood> bone, liver). Mean relative percentage bioavailability values of lead in the Butte mining waste soil were 20% based on the blood data. 9% based on the bone data, and 8% based on the liver data. The results of this study will provide the information needed to determine the significance of lead exposure from Butte soils in assessing human health risks as part of the Superfund Remedial Investigation/Feasibility Study process.

This study was conducted to determine the extent of arsenic (As) absorption from soil and house dust impacted by smelter activities near Anaconda, Montana. Female cynomolgus monkeys were given a single oral administration via gelatin capsules of soil (0.62 mg As/kg body wt) or house dust (0.26 mg As/kg body wt), or soluble sodium arsenate by the gavage or intravenous route of administration (0.62 mg As/kg body wt) in a crossover design with a minimum washout period of 14 days. Urine, feces, and cage rinse were collected at 24-hr intervals for 168 hr. Blood was collected at specified time points and area under the curves (AUCs) was determined. Arsenic concentrations for the first 120 hr, representing elimination of greater than 94% of the total administered dose for the three oral treatment groups, were <0.02 1 to 4.68 zg/ml for the urine and <0.24 to 31.1 μg/g for the feces. In general, peak concentrations of As in the urine and feces were obtained during the collection intervals of 0–24 and 24–72 hr, respectively. The main pathway for excretion of As for the intravenous and gavage groups was in the urine, whereas for the soil and dust groups, it was in the feces. Mean absolute percentage bioavailability values based on urinary excretion data were 68, 19, and 14% for the gavage, house dust, and soil treatments, respectively, after normal ization of the intravenous As recovery data to 100%. Correspond ing absolute bioavailability values based on blood were 91, 10, and 11%. The bioavailabiity of soil and house dust As relative to soluble As (by gavage) was between 10 and 30%, depending upon whether urinary or blood values were used. These findings suggest that risks associated with the ingestion of As in soil or dust will be reduced compared to ingestion of comparable quantities of As in drinking water.

Octadecylsilane was chemically bonded in situ on cation and anion exchange packings. The columns were tested for the liquid chromatographic separations of neutral and charged organic solutes which included nucleotides, polynuclear aromatic hydrocarbons, amines, carboxylic acids, and organometallic compounds. While some separations were effected predominantly by either the ion exchange sites or the reverse phase moieties, most separations appeared to be the combined effects of both stationary phases. The reverse phase partitioning, apparently induced by the solvophobic interaction, can make the elution volume and order of a charged solute significantly different from that found in a conventional ion exchange column. The mixed mode of ion exchange and reverse phase solvophobic interactions are illustrated.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The in vitro spllceosome assembly pathway is conserved between yeast and mammals as U1 and U2 snRNPs associate with the pre-mRNA prior to U5 and U4/U6 snRNPs. In yeast, U1 snRNP-pre-mRNA complexes are the first splicing complexes visualized on native gels, and association with U1 snRNP apparently commits pre-mRNA to the spliceosome assembly pathway. The current study addresses U2 snRNP addition to commitment complexes. We show that commitment complex formation is relatively slow and does not require ATP, whereas U2 snRNP adds to the U1 snRNP complexes in a reaction that is relatively fast and requires ATP or hydrolyzable ATP analogs. In vitro spliceosome assembly was assayed In extracts derived from strains containing several U1 sRNA mutations. The results were consistent with a critical role for U1 snRNP in early complex formation. A mutation that disrupts the base-pairing between the 5′ end of U1 snRNA and the 5′ splice site allows some U2 snRNP addition to bypass the ATP requirement, suggesting that ATP may be used to destablize certain U1 snRNP:pre-mRNA interactions to allow subsequent U2 snRNP addition.

This study determined the extent of arsenic (As) absorption from soil from Anaconda, Montana. Prepubescent male and female SPF New Zealand White rabbits (5/sex/group) were given a single oral (capsule) administration of soil (3900 ppm As) at three different dose levels (0.2, 0.5, and 1.0 g of soil/kg, corresponding to 0.78, 1.95, and 3.9 mg As/kg, respectively). Standard groups included untreated controls, an intravenous sodium arsenate group (1.95 mg As/kg), and a gavage sodium arsenate group (1.95 mg As/kg). Urine, cage rinse, and feces were collected at 24-hr intervals for 5 days and were analyzed for total As concentration. Clinical signs, body weights, and food consumption for treated animals were similar to controls. Maximum As concentrations were obtained over the initial 24-hr collection interval. A dose-dependent delay in urinary As excretion, the major elimination pathway, was observed in the oral soil group compared to that in the gavage group. For the animals in the soil groups, approximately 80% of the administered As dose was eliminated in the feces compared to approximately 10 and 50% for the intravenous and oral gavage groups, respectively. The relative oral bioavailabilities (±SD) of As in the gavage and test soil groups based on comparison with excreta data from the intravenous group were approximately 50±5.7 and 24±3.2%, respectively (after normalization of intravenous group's As recovery data to 100%). These results indicated that As in the soil was probably in a less soluble and therefore a less absorbable form than sodium arsenate.

Capacity factors of phenylalkylammonium and phenylammonium ions are linearly related to the reciprocal of the mobile phase eluent cation concentration for methanol-water mobile phases on a silica-based octadecyl column. Intercepts of these curves are considered to be capacity factors for pure reversed-phase interaction. Slopes of the curves are used to measure ion exchange tendency. The results indicate that ion exchange is aided by solvophobicity of the eluite.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Starting from the known spirolactone (I) and the carvone‐derivative (II), the pentacyclic dihydroxy ketoaldehyde (III) is prepared in its racemic and both optically active forms.

The paper reports a retrosynthetic analysis that leads to the conception of a synthetic strategy for the construction of ryanodol (Ia), the diterpene of ryanodine (Ib), a natural product isolated from Ryania speciosa.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A method of bioavailability estimation is presented in which a physiologically based kinetic model of lead kinetics is fit simultaneously to blood and bone lead concentrations after a period of exposure to dietary lead. Optimization of the simultaneous fit, varying only fractional absorption, gives the best estimate of fractional bioavailability for each treatment group. The analysis was applied to data from three separate studies in which rats were fed for 30 consecutive days purified diets containing lead added as lead acetate, mine waste-contaminated test soils, or mine waste itself. Fractional absorption decreased as lead intake increased, regardless of the source of the lead; but the magnitude of this dose dependence was lead source-dependent. There were no differences in lead absorption by male and female rats when lead intake was expressed per unit body weight. Fractional absorption varied from 4 to 5%, at low exposure rates (1–2 mg lead/kg/day) when lead acetate was added to the diet, to 0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminated test soil was added to the diet. Comparison of the results of this analysis with the results of a more conventional analysis, in which the bone and blood lead concentrations were separately compared with bone and blood lead concentrations in rats given daily injections of lead acetate intravenously for 29 consecutive days, demonstrated that the standard analysis failed to reveal the dose dependence of fractional absorption.

Agglomeration of particles in an HPLC packing slurry produces a catastrophic effect on column efficiency. The agglomerative phenomenon is believed to be caused by coulombic attraction forces between particies. Organic acids minimized the particle agglomeration by decreasing such attraction forces through protonation of gel surface negative sites. Column efficiency increased linearly with acid volume until a maximum value was reached. Two types of stable slurries were developed using specific organic acids as the slurry solvent. A combination of n-heptanoic acid and dichioroacetic acid was used to slurry reversed phase materials. Dichioroacetic acid was used to slurry normal-phase materials. These two system resulted in both stable slurries and reproducible, efficient, easily packed HPLC columns when used with a variety of commercial packing materials.

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