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Biomedical subjects

R V Jensen

Publications and source records attributed to R V Jensen.

10 recordsLinked to original sources

Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease.

Huntington's disease (HD) is an autosomal dominant disorder caused by an expansion of glutamine repeats in ubiquitously distributed huntingtin protein. Recent studies have shown that mutant huntingtin interferes with the function of widely expressed transcription factors, suggesting that gene expression may be altered in a variety of tissues in HD, including peripheral blood. Affymetrix and Amersham Biosciences oligonucleotide microarrays were used to analyze global gene expression in blood samples of HD patients and matched controls. We identified 322 mRNAs that showed significantly altered expression in HD blood samples, compared with controls (P < 0.0005), on two different microarray platforms. A subset of up-regulated mRNAs selected from this group was able to distinguish controls, presymptomatic individuals carrying the HD mutation, and symptomatic HD patients. In addition, early presymptomatic subjects showed gene expression profiles similar to those of controls, whereas late presymptomatic subjects showed altered expression that resembled that of symptomatic HD patients. These elevated mRNAs were significantly reduced in HD patients involved in a dose-finding study of the histone deacetylase inhibitor sodium phenylbutyrate. Furthermore, expression of the marker genes was significantly up-regulated in postmortem HD caudate, suggesting that alterations in blood mRNAs may reflect disease mechanisms observed in HD brain. In conclusion, we identified changes in blood mRNAs that clearly distinguish HD patients from controls. These alterations in mRNA expression correlate with disease progression and response to experimental treatment. Such markers may provide clues to the state of HD and may be of predictive value in clinical trials.

Adult↗

Sex-related differences in gene expression in salivary glands of BALB/c mice.

Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P < 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.

Animals↗

Influence of androgens on gene expression in the BALB/c mouse submandibular gland.

Androgens have profound effects on the murine submandibular gland. Our objective was to determine the nature and extent of androgen control of gene expression in the submandibular gland, and to explore the degree to which this might account for known sex differences. Orchiectomized male BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 days. Glands were collected, and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs by CodeLink microarrays, and the data were evaluated with GeneSifter. Androgens significantly (p < 0.05) influenced the expression of over 1300 genes, and many (n = 366) of the genes differentially regulated by androgen treatment were also differentially expressed in males compared with the females in our previous study. These findings support our hypotheses that testosterone extensively influences gene expression in the male submandibular gland, and that many of the sex differences are due to androgens.

Animals↗

Exact, convergent periodic-orbit expansions of individual energy eigenvalues of regular quantum graphs.

We present exact, explicit, convergent periodic-orbit expansions for individual energy levels of regular quantum graphs in the paper. One simple application is the energy levels of a particle in a piecewise constant potential. Since the classical ray trajectories (including ray splitting) in such systems are strongly chaotic, this result provides an explicit quantization of a classically chaotic system.

Journal Article↗

Explicitly solvable cases of one-dimensional quantum chaos.

We identify a set of quantum graphs with unique and precisely defined spectral properties called regular quantum graphs. Although chaotic in their classical limit with positive topological entropy, regular quantum graphs are explicitly solvable. The proof is constructive: we present exact, convergent periodic orbit expansions for individual energy levels, thus obtaining an analytical solution for the spectrum of regular quantum graphs that is complete, explicit, and exact.

Journal Article↗

Correcting for signal saturation errors in the analysis of microarray data.

A variety of technical errors have arisen in data analysis when using cDNA or oligonucleotide microarrays. One of the most insidious problems is the saturation of the hybridization signal of high-abundant transcripts. This problem arises from the truncation of the laser fluorescence signal. When the hybridization signal on the microarray is very strong, this truncation can result in serious consequences that may not be readily apparent to the user. As an illustration of this problem, two subclasses of normal human tissue samples (six liver and six lung samples) were analyzed with GeneChip probe arrays to evaluate the patterns of expression for approximately 7000 human genes. Five of these data sets were found to suffer from signal truncation. This caused several tissues to be incorrectly classified using hierarchical clustering. To rectify this problem so that the gene expression data could be properly compared and clustered, we developed a "filtering" procedure that identifies a subset of genes least affected by the signal saturation. This filtering procedure can be obtained at www.hugeindex.org.

Aged↗

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Cluster Analysis↗

EBP2 is a member of the yeast RRB regulon, a transcriptionally coregulated set of genes that are required for ribosome and rRNA biosynthesis.

In an effort to identify sets of yeast genes that are coregulated across various cellular transitions, gene expression data sets derived from yeast cells progressing through the cell cycle, sporulation, and diauxic shift were analyzed. A partitioning algorithm was used to divide each data set into 24 clusters of similar expression profiles, and the membership of the clusters was compared across the three experiments. A single cluster of 189 genes from the cell cycle experiment was found to share 65 genes with a cluster of 159 genes from the sporulation data set. Many of these genes were found to be clustered in the diauxic-shift experiment as well. The overlapping set was enriched for genes required for rRNA biosynthesis and included genes encoding RNA helicases, subunits of RNA polymerases I and III, and rRNA processing factors. A subset of the 65 genes was tested for expression by a quantitative-relative reverse transcriptase PCR technique, and they were found to be coregulated after release from alpha factor arrest, heat shock, and tunicamycin treatment. Promoter scanning analysis revealed that the 65 genes within this ribosome and rRNA biosynthesis (RRB) regulon were enriched for two motifs: the 13-base GCGATGAGATGAG and the 11-base TGAAAAATTTT consensus sequences. Both motifs were found to be important for promoting gene expression after release from alpha factor arrest in a test rRNA processing gene (EBP2), which suggests that these consensus sequences may function broadly in the regulation of a set of genes required for ribosome and rRNA biosynthesis.

Algorithms↗

Dimensional complexity of EEG waveforms in neuroleptic-free schizophrenic patients and normal control subjects.

Dimensional complexity reflects the number of independent variables contributing to a dynamic process. EEG epochs recorded from 12 neuroleptic-free schizophrenic patients and 11 normal control subjects were Laplacian-filtered to highlight activity specific to prefrontal and parietal areas, and dimensional complexity measures of the resulting signals were then derived. Complexity of EEG waveforms generated by schizophrenic patients was depressed relative to that of normal subjects, especially in left frontal and right parietal regions. These data suggest that complexity of underlying is also reduced.

Adult↗