Predicting unknown species numbers using discovery curves.

A common approach to estimating the total number of extant species in a taxonomic group is to extrapolate from the temporal pattern of known species descriptions. A formal statistical approach to this problem is provided. The approach is applied to a number of global datasets for birds, ants, mosses, lycophytes, monilophytes (ferns and horsetails), gymnosperms and also to New World grasses and UK flowering plants.

BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction.

The mammary glands develop initially as buds arising from the ventral embryonic epidermis. Recent work has shed light on signaling pathways leading to the patterning and formation of the mammary placodes and buds in mouse embryos. Relatively little is known of the signaling pathways that initiate branching morphogenesis and the formation of the ducts from the embryonic buds.

Holiday waistline. Jolly, fit and fat: should we be singing the "Santa Too Fat Blues"?

Santa Claus's apparent weight gain, much chronicled in the popular media, raises the question of whether his jolly persona could be at risk. We investigate why Santa remains jolly, even though he is becoming obese, and what factors could be keeping him upbeat. Measures of body mass, mental health and physical activity were collected from a representative cohort of Canadian adults surveyed in 1988 and again 15 years later.

Hybridization, polyploidy, and the evolution of sexual systems in Mercurialis (Euphorbiaceae).

Hybridization and polyploidy are widely believed to be important sources of evolutionary novelty in plant evolution. Both can lead to novel gene combinations and/or novel patterns of gene expression, which in turn provide the variation on which natural selection can act. Here, we use nuclear and plastid gene trees, in conjunction with morphological data and genome size measurements, to show that both processes have been important in shaping the evolution of the angiosperm genus Mercurialis, particularly a clade of annual lineages that shows exceptional variation in the sexual system.

Rat toxicogenomic study reveals analytical consistency across microarray platforms.

To validate and extend the findings of the MicroArray Quality Control (MAQC) project, a biologically relevant toxicogenomics data set was generated using 36 RNA samples from rats treated with three chemicals (aristolochic acid, riddelliine and comfrey) and each sample was hybridized to four microarray platforms. The MAQC project assessed concordance in intersite and cross-platform comparisons and the impact of gene selection methods on the reproducibility of profiling data in terms of differentially expressed genes using distinct reference RNA samples. The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons.

The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements.

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues.

The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling.

Bone morphogenetic protein 2 (BMP-2) plays a critical role in osteoblast function. In Drosophila, Cubitus interruptus (Ci), which mediates hedgehog signaling, regulates gene expression of dpp, the ortholog of mammalian BMP-2. Null mutation of the transcription factor Gli2, a mammalian homolog of Ci, results in severe skeletal abnormalities in mice.

Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial.

Context: During a clinical trial of a novel hydrocodone/acetaminophen combination, a high incidence of serum alanine aminotransferase (ALT) elevations was observed.

Objective: To characterize the incidence and magnitude of ALT elevations in healthy participants receiving 4 g of acetaminophen daily, either alone or in combination with selected opioids, as compared with participants treated with placebo.

Design, Setting, And Participants: A randomized, single-blind, placebo-controlled, 5-treatment, parallel-group, inpatient, diet-controlled (meals provided), longitudinal study of 145 healthy adults in 2 US inpatient clinical pharmacology units.

Locke and botany.

This paper argues that the English philosopher John Locke, who has normally been thought to have had only an amateurish interest in botany, was far more involved in the botanical science of his day than has previously been known. Through the presentation of new evidence deriving from Locke's own herbarium, his manuscript notes, journal and correspondence, it is established that Locke made a modest contribution to early modern botany. It is shown that Locke had close and ongoing relations with the Bobarts, keepers of the Oxford Botanic Garden, and that Locke distributed seeds and plant parts to other botanists, seeds of which the progeny almost certainly ended up in the most important herbaria of the period.

E11/gp38 selective expression in osteocytes: regulation by mechanical strain and role in dendrite elongation.

Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells.

Sexual systems and population genetic structure in an annual plant: testing the metapopulation model.

The need for reproductive assurance during dispersal, along with the pressure of local mate competition, means that the importance of frequent or repeated colonization is implicit in the literature on sexual system evolution. However, there have been few empirical tests of the association between colonization history and sexual system in plants, and none within a single species. Here we use patterns of genetic diversity to provide such a test in the Mercurialis annua species complex, which spans the range of systems from self-compatible monoecy through androdioecy to dioecy.

The population genetics of sporophytic self-incompatibility in Senecio squalidus L. (Asteraceae): the number, frequency, and dominance interactions of S alleles across its British range.

Sporophytic self-incompatibility (SSI) was studied in 11 British Senecio squalidus populations to quantify mating system variation and determine how its recent colonization of the United Kingdom has influenced its mating behavior. S allele number, frequency, and dominance interactions in populations were assessed using full diallels of controlled pollinations. A mean of 5.

PRISM/PRDM6, a transcriptional repressor that promotes the proliferative gene program in smooth muscle cells.

Smooth muscle cells (SMCs) display remarkable phenotypic diversity and plasticity and can readily switch between proliferative and differentiated states in response to extracellular cues. In an effort to identify novel transcriptional regulators of smooth muscle phenotypes, we compared the gene expression profiles of arterial and venous SMCs by microarray-based transcriptional profiling. Among numerous genes displaying distinct expression patterns in these two SMC types, we discovered an expressed sequence tag encoding a previously uncharacterized zinc finger protein belonging to the PRDM (PRDI-BF1 and RIZ homology domain) family of chromatin-remodeling proteins and named it PRISM (PR domain in smooth muscle).

Modes and rates of selfing and associated inbreeding depression in the self-incompatible plant Senecio squalidus (Asteraceae): a successful colonizing species in the British Isles.

The strength of the self-incompatibility (SI) response in Senecio squalidus was measured across its British range. Geographic variation in SI was investigated and the extent and inheritance of pseudo-self-compatibility (PSC) and inbreeding depression were determined. Mean self-fruit-set per capitulum was calculated for individuals and sample populations.

Dkk2 has a role in terminal osteoblast differentiation and mineralized matrix formation.

Human and mouse genetic and in vitro evidence has shown that canonical Wnt signaling promotes bone formation, but we found that mice lacking the canonical Wnt antagonist Dickkopf2 (Dkk2) were osteopenic. We reaffirmed the finding that canonical Wnt signaling stimulates osteogenesis, including the differentiation from preosteoblasts to osteoblasts, in cultured osteoblast differentiation models, but we also found that canonical Wnts upregulated the expression of Dkk2 in osteoblasts. Although exogenous overexpression of Dkk before the expression of endogenous canonical Wnt (Wnt7b) suppressed osteogenesis in cultures, its expression after peak Wnt7b expression induced a phenotype resembling terminal osteoblast differentiation leading to mineralization.

Microarray scanner calibration curves: characteristics and implications.

Background: Microarray-based measurement of mRNA abundance assumes a linear relationship between the fluorescence intensity and the dye concentration. In reality, however, the calibration curve can be nonlinear.

Results: By scanning a microarray scanner calibration slide containing known concentrations of fluorescent dyes under 18 PMT gains, we were able to evaluate the differences in calibration characteristics of Cy5 and Cy3.

Clinical pharmacology and pharmacokinetics of once-daily hydromorphone hydrochloride extended-release capsules.

Hydromorphone hydrochloride extended release (HHER) is a multiparticulate melt-extrusion pellet capsule formulation administered q24h. Study 1 investigated the bioavailability of 24-mg HHER fed, as well as 24-mg and 12-mg HHER and 8-mg hydromorphone hydrochloride immediate-release (HHIR) tablets fasting. No clinically significant food effect was observed on hydromorphone C(max) or AUC for the 24-mg HHER, and dose proportionality (AUC) was demonstrated between 12- and 24-mg HHER.

Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling.

The loss of the SOST gene product sclerostin leads to sclerosteosis characterized by high bone mass. In this report, we found that sclerostin could antagonize canonical Wnt signaling in human embryonic kidney A293T cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by overexpression of Wnt co-receptor low density lipoprotein receptor-related protein (LRP) 5.

Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo.

Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is mechanically responsive. To study osteocyte-specific and mechanically regulated DMP1 gene expression, the transcriptional activity of three cis-regulatory regions was first examined in an osteoblast differentiation model in vitro using a green fluorescent protein (GFP) reporter. Expression of the -9624 to +1996 bp (10 kb) and -7892 to +4439 bp (8 kb) DMP1 cis-regulatory regions dramatically increased in areas of mineralized matrix, in dendritic, osteocyte-like cells.

Locating Ath8, a locus for murine atherosclerosis susceptibility and testing several of its candidate genes in mice and humans.

A previous study revealed that the difference in susceptibility to atherosclerotic lesions between inbred mouse strains SM/J and NZB/BlNJ was determined by one major locus (Ath8). In this study a (SM/J x NZB/BlNJ) F(1) x SM/J backcross localized Ath8 by quantitative trait locus mapping to chromosome 4 with a suggestive LOD score of 2.7.

Models of steroid binding based on the minimum deviation of structurally assigned 13C NMR spectra analysis (MiDSASA).

This paper develops a quantitative k-nearest neighbors modeling technique. The technique is used to demonstrate that a compound's biological binding activity to a receptor can be calculated from the minimum of the square root of the sum of squared deviations (SSSD) of a structurally assigned chemical shift on a template between the unknown compound to be predicted and a set of known compounds with known activities. When building models of biological activity, nonlinear relationships are built into the input training data.

Gene structure and molecular analysis of Arabidopsis thaliana ALWAYS EARLY homologs.

Drosophila always early (aly) is essential for spermatogenesis, and is related to the LIN-9 protein of Caenorhabditis elegans; lin-9 is a class B Synthetic Multivulva gene (synMuvB) required for gonadal sheath development. Aly/LIN-9 have two conserved regions, called domains 1 and 2, which have been identified in homologous proteins from several multicellular eukaryotes, including the model plant Arabidopsis thaliana. We cloned and sequenced cDNAs of three different A.

Modelling the costs of fox predation and preventive measures on sheep farms in Britain.

Economic analysis is a useful tool to aid decisions on what to do about wildlife impacts, such as those of vertebrate predators on livestock farmers. The case-study of lamb predation by foxes in Britain is used to develop a theoretical economic model, with the aim of determining a financially optimal solution to minimise the total costs of livestock predation at the farm-level. Total costs include output losses and expenditure on preventive and control measures, in this case indoor housing and lethal fox control.

Development of public toxicogenomics software for microarray data management and analysis.

A robust bioinformatics capability is widely acknowledged as central to realizing the promises of toxicogenomics. Successful application of toxicogenomic approaches, such as DNA microarray, inextricably relies on appropriate data management, the ability to extract knowledge from massive amounts of data and the availability of functional information for data interpretation. At the FDA's National Center for Toxicological Research (NCTR), we are developing a public microarray data management and analysis software, called ArrayTrack.