The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR).

Induction of cytochrome P450 3A (CYP3A) by xenobiotics may lead to clinically relevant drug interactions. In contrast with other CYP3A family members, studies on the inducibility of CYP3A5 indicate conflicting results. We report the induction of CYP3A5 mRNA in 13 of 16 hepatocyte preparations exposed to rifampin.

Model validation of biological pathways using Petri nets--demonstrated for apoptosis.

This paper demonstrates the first steps of a new integrating methodology to develop and analyse models of biological pathways in a systematic manner using well established Petri net technologies. The whole approach comprises step-wise modelling, animation, model validation as well as qualitative and quantitative analysis for behaviour prediction. In this paper, the first phase is addressed how to develop and validate a qualitative model, which might be extended afterwards to a quantitative model.

Limited contribution of CYP3A5 to the hepatic 6beta-hydroxylation of testosterone.

The polymorphic expression of CYP3A5 in human livers is well established, but its significance for the entire hepatic CYP3A activity is disputed. We investigated the contribution of CYP3A5 to the CYP3A activity assessed as 6beta-hydroxylation of testosterone using baculovirus-expressed CYP3A4 and CYP3A5 and microsomes isolated from 47 Caucasian human livers. Under comparable conditions, the specific activities of baculovirus-expressed CYP3A4 and CYP3A5 were nearly identical.

PTGL--a web-based database application for protein topologies.

Protein Topology Graph Library (PTGL) is a database application for the representation and retrieval of protein topologies. Protein topologies are based on a graph-theoretical protein model at secondary structure level. Different views on protein topology are given by four linear notations for their characterization.

Dual-task slowing and the effects of cross-task compatibility.

Recent studies have shown that visual encoding requires central processing, evidenced in the form of dual-task interference on response processes of a reaction time (RT) task. We report two experiments examining such dual-task interference: (1) at global level, to establish that visual encoding indeed requires central processing; and (2) at code level, to see whether two tasks may share the same representational codes. To this end, we manipulated the compatibility relation between the response codes for an auditory choice RTtask and the stimulus codes for a logically independent visual motion detection task.

The costs of changing the representation of action: response repetition and response-response compatibility in dual tasks.

In 5 experiments, the authors investigated the costs associated with repeating the same or a similar response in a dual-task setting. Using a psychological refractory period paradigm, they obtained response-repetition costs when the cognitive representation of a specific response (i.e.

Different mechanisms of cyclin D1 overexpression in multiple myeloma revealed by fluorescence in situ hybridization and quantitative analysis of mRNA levels.

The t(11;14)(q13;q32) is the most common translocation in multiple myeloma (MM), resulting in up-regulation of cyclin D1. We used a segregation fluorescence in situ hybridization (FISH) assay to detect t(11;14) breakpoints in primary MM cases and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify cyclin D1 and MYEOV (myeloma overexpressed) expression, another putative oncogene located on chromosome 11q13. High levels of cyclin D1 mRNA (cyclin D1/TBP [TATA box binding protein] ratio > 95) were found exclusively in the presence of a t(11;14) translocation (11/48 cases; P <.

Linear interpolation error in measured surfaces in a dental erosion study.

An extensive palatal erosion study, which is currently being undertaken at the University of Dundee, aims to detect erosion through the precise mapping of replicas of children's incisors. All perceived sources of error are being scrutinised closely. The error due to the interpolation of surface positions from discrete point measurements has been investigated so that its contribution to the erosion estimates can be gauged.

Inhibition of response mode in task switching.

Task inhibition was explored in two experiments that employed a paradigm in which participants switched among three tasks. Two tasks required manual choice responses based on numerical judgment (parity or magnitude), whereas a third task required an unconditional double-press of both response keys. Both experiments showed that switching to a just-abandoned task (n-2 task repetition) generally leads to a performance cost relative to switching to another task.

Overexpression of the embryonic-lethal abnormal vision-like protein HuR in ovarian carcinoma is a prognostic factor and is associated with increased cyclooxygenase 2 expression.

The human embryonic-lethal abnormal vision-like protein HuR is involved in the regulation of mRNA turnover and serves as a shuttling protein between the nucleus and the cytoplasm that stabilizes mRNAs containing adenine- and uridine-rich elements in their 3' untranslated region. We have shown recently that expression of cyclooxygenase (COX)-2 is related to poor prognosis in ovarian carcinoma. Other studies have shown that the COX-2 mRNA contains an adenine- and uridine-rich element and is stabilized by HuR.

Steady state analysis of metabolic pathways using Petri nets.

Computer assisted analysis and simulation of biochemical pathways can improve the understanding of the structure and the dynamics of cell processes considerably. The construction and quantitative analysis of kinetic models is often impeded by the lack of reliable data. However, as the topological structure of biochemical systems can be regarded to remain constant in time, a qualitative analysis of a pathway model was shown to be quite promising as it can render a lot of useful knowledge, e.

Anticipated action effects affect the selection, initiation, and execution of actions.

This study investigated the impact of contingent action effects on response production. In Experiment 1 responses of varying intensity were initiated faster when contingently followed by auditory effects of corresponding rather than of noncorresponding intensity. This response-effect (R-E) compatibility influence was robust with respect to practice, and it was not due to persisting influences of preceding R-E episodes.

Induction of G0/G1 cell cycle arrest in ovarian carcinoma cells by the anti-inflammatory drug NS-398, but not by COX-2-specific RNA interference.

Cyclooxygenases, particularly COX-2, play an important role in tumor development and progression. We have previously shown that COX-2 expression is an independent prognostic factor in human ovarian carcinoma. In this study, we investigated the effects of the inhibition of COX isoforms by the NSAID NS-398 as well as by COX-isoform-specific RNA interference (RNAi) in the human ovarian carcinoma cell lines OVCAR-3 and SKOV-3.

Identification of transcripts from a subtraction library which might be responsible for the mild phenotype in an intrafamilially variable course of Duchenne muscular dystrophy.

While frame-shift mutations are usually found in Duchenne muscular dystrophy (DMD), in-frame mutations are associated with the less severe phenotype of Becker's muscular dystrophy. Exceptions have been reported in both directions suggesting the existence of modifying genes, which might be helpful for innovation of new therapeutic strategies. We report on the very rare case of an intrafamilially different course of DMD, with the younger brother being far less affected than the older one when compared at the same age.

When the same response has different meanings: recoding the response meaning in the lateral prefrontal cortex.

The ability to adapt our behavioral repertoire to different situations and tasks is crucial for our behavioral control. Since the same motor behavior can have different meanings in different task situations, we often have to change the meaning of our responses when we get into a different task context. In a functional MRI experiment we manipulated this response recoding process.

Equivalence of cognitive processes in brain imaging and behavioral studies: evidence from task switching.

A growing number of studies on the higher-order cognitive functions of the human brain use brain-imaging techniques, such as functional magnetic resonance imaging (fMRI). For the validity and generality of fMRI results, it is important that the relevant cognitive processes are equivalent to those functioning in typical settings used in behavioral research. This equivalence could be, for example, endangered by different spatial frames of reference when lying in the scanner.

The role of external cues for endogenous advance reconfiguration in task switching.

Most studies of task-set switching rely on cuing paradigms, in which external cues indicate the upcoming task. The present study used an entirely predictable task sequence in a variant of the alternating-runs paradigm of Rogers and Monsell (1995). Preparation effects with purely internal memory cues were compared with those in another experimental group with additional external cues presented prior to the stimulus.

Cytokine-suppressive anti-inflammatory drugs (CSAIDs) inhibit invasion and MMP-1 production of ovarian carcinoma cells.

The development of therapeutic strategies for inhibition of peritoneal dissemination and invasion would be central for the treatment of ovarian carcinoma. In the microenvironment of ovarian carcinomas, various inflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) are present. In this study we investigated the role of inflammatory cytokines in the regulation of invasion of SKOV-3 ovarian carcinoma cells in-vitro.

The role of temporal unpredictability for process interference and code overlap in perception-action dual tasks.

Two experiments explore interference in dual tasks. The first task required perceptual judgment of the movement direction (left vs right) of a briefly presented stimulus; the second task was a tone-discrimination reaction-time (RT) task. Participants reported their judgment at leisure.

The role of response selection for inhibition of task sets in task shifting.

Response selection in task shifting was explored using a go/no-go methodology. The no-go signal occurred unpredictably with stimulus onset so that all trials required task preparation but only go trials required response selection. Experiment 1 showed that shift costs were absent after no-go trials, indicating that response processes are crucial for shift costs.

Verbal response-effect compatibility.

Ideomotor theory states that motor responses are activated by an anticipation of their sensory effects. We assumed that anticipated effects would produce response-effect (R-E) compatibility when there is dimensional overlap of effects and responses. In a four-choice task, visual digit stimuli called for verbal responses (color names).

Increase of functional diversity by alternative splicing.

A large-scale analysis of protein isoforms arising from alternative splicing shows that alternative splicing tends to insert or delete complete protein domains more frequently than expected by chance, whereas disruption of domains and other structural modules is less frequent. If domain regions are disrupted, the functional effect, as predicted from 3D structure, is frequently equivalent to removal of the entire domain. Also, short alternative splicing events within domains, which might preserve folded structure, target functional residues more frequently than expected.

Gamma-tubulin37C and gamma-tubulin ring complex protein 75 are essential for bicoid RNA localization during drosophila oogenesis.

bicoid (bcd) RNA localization requires the activity of exuperantia and swallow at sequential steps of oogenesis and is microtubule dependent. In a genetic screen, we identified two novel genes essential for bcd RNA localization. They encode maternal gamma-Tubulin37C (gammaTub37C) and gamma-tubulin ring complex protein 75 (Dgrip75), both of which are gamma-tubulin ring complex components.

Theoretical analysis of alternative splice forms using computational methods.

Nowadays understanding alternative splicing is one of the greatest challenges in biology, because it is a genetic process much more important than thought at the time of its discovery. In this paper, we explain the approach of using the different available databases and software tools to start a large scale investigation of alternative splice forms. To collect information about alternative splicing we investigated known data in the databases using different computational methods.

Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA.

The elucidation of the individual contributions of the four CYP3A genes to the overall CYP3A activity has been hampered by similarities in their sequence and function. We investigated the expression of CYP3A mRNA species in the liver and in various other tissues using gene-specific TaqMan probes. CYP3A4 transcripts were the most abundant CYP3A mRNA in each of the 63 white European livers tested and accounted on average for 95% of the combined CYP3A mRNA pool.