Disparities In Gene Expression Research Articles

A molecular viewpoint of the intricate relationships among HNSCC, HPV infections, and the oral microbiota dysbiosis

HPV infection and the type of host microbiota play a role in the formation of HNCs. In contrast to other forms of OSCC, where the relationship between HPV and the cancer is less obvious, HPV-HNSCC is a particular type of oropharyngeal cancer. HPV has infected a stratified squamous epithelium, which includes the throat, mouth, anogenital tract, respiratory tract, and skin on the hands and feet. HPV DNA was found in high amounts in the saliva and gargle samples of patients with HPV-related HNSCC. It has been discovered that the specificity of oral mRNA (HPV) and HPV DNA identification varies from 23 % to 82 % in the identification of OPSCCs. The higher rate of HPV transmission through vaginal-oral compared to penile-oral sexual activity may be the reason for the difference in HPV-positive HNSCC patients between males and females. The researchers postulate that HPV-inactive tumours signify an advanced stage of HPV-positive HNSCC, which explains why there are racial disparities in gene expression that correspond to different disease progressions in Black and White patients. The increase of CD8+ T cells in the cancer microenvironment, linked to P16 activation, extends life expectancy in OSCC. tumour markers methylation caused by HPV and suggested using them as possible HNC biomarkers. Fusobacterium levels are much higher in patients with OSCC, while Actinobacteria phylum and Firmicutes are significantly lower. It also serves as a biomarker for notable variations found in Firmicutes, Actinobacteria, Fusobacteriales, Fusobacteriia, Fusobacterium, and Fusobacteriaceae. Therefore, based on this we evidence, we could investigate the role of oral microbiota as a maker for the HPV associated HNSCC.

Defense strategies against sweet potato chlorotic stunt and pakakuy virus coinfection unraveled

AbstractThis study into the response of two Ipomoea batatas (L.) Lam cultivars, Melinda and Tio Joe, to coinfection with sweet potato chlorotic stunt virus (SPCSV) and sweet potato pakakuy virus (SPPV), employed a comprehensive approach encompassing symptomatology, real‐time quantitative polymerase chain reaction, metagenomics, and transcriptomics. SPCSV is a quarantine virus with synergistic effects, which decimate yields. SPPV is the most prevalent DNA virus in sweet potato germplasm, with a tendency to persist in meristems, posing a significant risk for germplasm transfer between territories. Graft inoculation experiments revealed that while Tio Joe remained asymptomatic for 12 weeks and suppressed virus replication, Melinda displayed symptoms early on and exhibited high virus titers. Metagenomic analyses corroborated these observations and confirmed that SPCSV and SPPV were responsible. Transcriptomic analysis unveiled disparities in gene expression between Melinda and Tio Joe. Differential gene expression was heightened and altered in Melinda as the viruses disrupted its gene expression. Its defense strategies, such as inducing abscisic acid signaling, were insufficient to overcome disruptive viral effects like oxidative stress, rendering it susceptible. In contrast, Tio Joe had relatively stable differential gene expression, indicating resistance to SPPV–SPCSV coinfection. Overexpressed genes such as sirtuin, rapid alkalization factor, and nuclear pore anchor triggered quantitative resistance, supported with enriched organelles such as mitochondrion and pathways such as proteasome and cutin, suberine, and wax biosynthesis. Tio Joe maintained its genome integrity and inhibited viral replication by tightly controlling gene expression and preventing reactive oxygen species accumulation.

Unveiling heterogeneity and prognostic markers in ductal breast cancer through single-cell RNA-seq

BackgroundBreast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets.MethodsBioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes.ResultsThe analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells.ConclusionThis study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.

Assessment of P-glycoprotein function using canine intestinal organoid-derived epithelial interfaces

P-glycoprotein (P-gp), a multidrug efflux pump encoded by the ABCB1 (formerly MDR1) gene, plays a crucial role in limiting drug absorption and eliminating toxic compounds in both humans and dogs. However, species-specific differences in P-gp substrates necessitate the development of canine-specific evaluation systems. Canine intestinal organoids derived monolayers offer a promising platform for studying drug transport, yet P-gp-mediated transport in these models remains unexplored. We generated canine colonoid-derived 2D monolayers to investigate ABCB1 gene expression and P-gp function. We employed widely recognised P-gp substrates, Rhodamine 123 and Doxorubicin, in conjunction with the P-gp inhibitor PSC833 at Days 5 and 10 of culture. A significant increase in gene expression of P-gp encoded by the ABCB1 was noted on Day 10 compared to Day 5 of culture. Despite this disparity in gene expression, the transport activity of P-gp, as assessed by the efflux of Rhodamine 123 and Doxorubicin with PSC833 inhibition, did not exhibit significant differences between these two time points. However, the inhibition of P-gp function by PSC833 confirms the presence of functional P-gp in our model. Canine intestinal organoid-derived monolayers provide a valuable tool for investigating P-gp-mediated drug transport. These findings highlight the potential for predicting drug bioavailability and adverse reactions in veterinary medicine, aligning with principles of ethical and sustainable research.

Identification, Classification, and Transcriptional Analysis of Rab GTPase Genes from Tomato (Solanum lycopersicum) Reveals Salt Stress Response Genes.

Salinity in plants generates an osmotic and ionic imbalance inside cells that compromises the viability of the plant. Rab GTPases, the largest family within the small GTPase superfamily, play pivotal roles as regulators of vesicular trafficking in plants, including the economically important and globally cultivated tomato (Solanum lycopersicum). Despite their significance, the specific involvement of these small GTPases in tomato vesicular trafficking and their role under saline stress remains poorly understood. In this work, we identified and classified 54 genes encoding Rab GTPases in cultivated tomato, elucidating their genomic distribution and structural characteristics. We conducted an analysis of duplication events within the S. lycopersicum genome, as well as an examination of gene structure and conserved motifs. In addition, we investigated the transcriptional profiles for these Rab GTPases in various tissues of cultivated and wild tomato species using microarray-based analysis. The results showed predominantly low expression in most of the genes in both leaves and vegetative meristem, contrasting with notably high expression levels observed in seedling roots. Also, a greater increase in gene expression in shoots from salt-tolerant wild tomato species was observed under normal conditions when comparing Solanum habrochaites, Solanum pennellii, and Solanum pimpinellifolium with S. lycopersicum. Furthermore, an expression analysis of Rab GTPases from Solanum chilense in leaves and roots under salt stress treatment were also carried out for their characterization. These findings revealed that specific Rab GTPases from the endocytic pathway and the trans-Golgi network (TGN) showed higher induction in plants exposed to saline stress conditions. Likewise, disparities in gene expression were observed both among members of the same Rab GTPase subfamily and between different subfamilies. Overall, this work emphasizes the high degree of conservation of Rab GTPases, their high functional diversification in higher plants, and the essential role in mediating salt stress tolerance and suggests their potential for further exploration of vesicular trafficking mechanisms in response to abiotic stress conditions.

Phenotypic divergence between broiler and layer chicken lines is regulated at the molecular level during development

BackgroundUnderstanding the molecular underpinnings of phenotypic variations is critical for enhancing poultry breeding programs. The Brazilian broiler (TT) and laying hen (CC) lines exhibit striking differences in body weight, growth potential, and muscle mass. Our work aimed to compare the global transcriptome of wing and pectoral tissues during the early development (days 2.5 to 3.5) of these chicken lines, unveiling disparities in gene expression and regulation.ResultsDifferent and bona-fide transcriptomic profiles were identified for the compared lines. A similar number of up- and downregulated differentially expressed genes (DEGs) were identified, considering the broiler line as a reference. Upregulated DEGs displayed an enrichment of protease-encoding genes, whereas downregulated DEGs exhibited a prevalence of receptors and ligands. Gene Ontology analysis revealed that upregulated DEGs were mainly associated with hormone response, mitotic cell cycle, and different metabolic and biosynthetic processes. In contrast, downregulated DEGs were primarily linked to communication, signal transduction, cell differentiation, and nervous system development. Regulatory networks were constructed for the mitotic cell cycle and cell differentiation biological processes, as their contrasting roles may impact the development of distinct postnatal traits. Within the mitotic cell cycle network, key upregulated DEGs included CCND1 and HSP90, with central regulators being NF-κB subunits (RELA and REL) and NFATC2. The cell differentiation network comprises numerous DEGs encoding transcription factors (e.g., HOX genes), receptors, ligands, and histones, while the main regulatory hubs are CREB, AR and epigenetic modifiers. Clustering analyses highlighted PIK3CD as a central player within the differentiation network.ConclusionsOur study revealed distinct developmental transcriptomes between Brazilian broiler and layer lines. The gene expression profile of broiler embryos seems to favour increased cell proliferation and delayed differentiation, which may contribute to the subsequent enlargement of pectoral tissues during foetal and postnatal development. Our findings pave the way for future functional studies and improvement of targeted traits of economic interest in poultry.

Metabolic control analysis of L-tryptophan producing Escherichia coli applying targeted perturbation with shikimate

L-tryptophan production from glycerol with Escherichia coli was analysed by perturbation studies and metabolic control analysis. The insertion of a non-natural shikimate transporter into the genome of an Escherichia coli L-tryptophan production strain enabled targeted perturbation within the product pathway with shikimate during parallelised short-term perturbation experiments with cells withdrawn from a 15 L fed-batch production process. Expression of the shikimate/H+-symporter gene (shiA) from Corynebacterium glutamicum did not alter process performance within the estimation error. Metabolic analyses and subsequent extensive data evaluation were performed based on the data of the parallel analysis reactors and the production process. Extracellular rates and intracellular metabolite concentrations displayed evident deflections in cell metabolism and particularly in chorismate biosynthesis due to the perturbations with shikimate. Intracellular flux distributions were estimated using a thermodynamics-based flux analysis method, which integrates thermodynamic constraints and intracellular metabolite concentrations to restrain the solution space. Feasible flux distributions, Gibbs reaction energies and concentration ranges were computed simultaneously for the genome-wide metabolic model, with minimum bias in relation to the direction of metabolic reactions. Metabolic control analysis was applied to estimate elasticities and flux control coefficients, predicting controlling sites for L-tryptophan biosynthesis. The addition of shikimate led to enhanced deviations in chorismate biosynthesis, revealing a so far not observed control of 3-dehydroquinate synthase on L-tryptophan formation. The relative expression of the identified target genes was analysed with RT-qPCR. Transcriptome analysis revealed disparities in gene expression and the localisation of target genes to further improve the microbial L-tryptophan producer by metabolic engineering.

Transcriptome analysis reveals sexual disparities in gene expression in rat brain microvessels

Sex is an important determinant of brain microvessels (MVs) function and susceptibility to cerebrovascular and neurological diseases, but underlying mechanisms are unclear. Using high throughput RNA sequencing analysis, we examined differentially expressed (DE) genes in brain MVs from young, male, and female rats. Bioinformatics analysis of the 23,786 identified genes indicates that 298 (1.2%) genes were DE using False Discovery Rate criteria (FDR; p < 0.05), of which 119 (40%) and 179 (60%) genes were abundantly expressed in male and female MVs, respectively. Nucleic acid binding, enzyme modulator, and transcription factor were the top three DE genes, which were more highly expressed in male than female MVs. Synthesis of glycosylphosphatidylinositol (GPI), biosynthesis of GPI-anchored proteins, steroid and cholesterol synthesis, were the top three significantly enriched canonical pathways in male MVs. In contrast, respiratory chain, ribosome, and 3 ́-UTR-mediated translational regulation were the top three enriched canonical pathways in female MVs. Different gene functions of MVs were validated by proteomic analysis and western blotting. Our novel findings reveal major sex disparities in gene expression and canonical pathways of MVs and these differences provide a foundation to study the underlying mechanisms and consequences of sex-dependent differences in cerebrovascular and other neurological diseases.

SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

SARS-CoV-2 Infections: An ACE in the Hole and Systems Biology Studies—a Research Agenda

Origin of somatic transformation in germ cell tumor of testis (TGCT): Role of differentiation versus dedifferentiation in a mature teratoma.

410 Background: TGCT is a prototype stem-cell malignancy recapitulating the ontogeny of solid tumors. We studied the roles of differentiation versus dedifferentiation in a bona fide well-differentiated tumor, namely mature teratomas, associated with or without somatic transformation. Methods: Between 2001 and 2013, we identified 7 out of 13 cases in which teratoma and somatic transformation were present within the same residual tumor after chemotherapy and resected at our institution with sufficient quantity and quality for DNA and RNA analysis. We performed primary cell culture, flow cytometry, and xenografts to evaluate stem-ness biomarkers and tumor phenotypes of freshly resected mature teratomas. Results: We detected very few mutations within a preselected gene pool (T200) in all tumor samples. The "within patient mutation agreement" from a mutation matrix of 57 genes, in which at least one mutation occurred between teratoma and somatic transformation, was 86.2 to 94.8%. There was disparity in gene expression, including miR7-3HG, ARHGEF35, and DLX6, between the 7 matched tumor pairs (log2 fold change of about 2). Prospective primary cell culture studies using cell surface stem-ness markers (SSEA3, TRA1-60, Cripto-1, CD90, CD133, CD44) indicate presence of stem cells embedded within residual mature teratomas (n = 3) after chemotherapy. Conclusions: Molecular profiling confirms a common clonal origin between teratoma and somatic transformation but refutes the idea of dedifferentiation of teratoma to somatic transformation. Presence of stem cells embedded within mature teratomas and capable of differentiation into separate ontogenetic lineages could account for the origin of somatic transformation in TGCT.[Table: see text]

The histone code reader PHD finger protein 7 controls sex-linked disparities in gene expression and malignancy in Drosophila.

The notable male predominance across many human cancer types remains unexplained. Here, we show that Drosophila l(3)mbt brain tumors are more invasive and develop as malignant neoplasms more often in males than in females. By quantitative proteomics, we have identified a signature of proteins that are differentially expressed between male and female tumor samples. Prominent among them is the conserved chromatin reader PHD finger protein 7 (Phf7). We show that Phf7 depletion reduces sex-dependent differences in gene expression and suppresses the enhanced malignant traits of male tumors. Our results identify potential regulators of sex-linked tumor dimorphism and show that these genes may serve as targets to suppress sex-linked malignant traits.

MP06-03 RACE BASED DISPARITIES IN GENE EXPRESSION AND MUTATIONS IN BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2018MP06-03 RACE BASED DISPARITIES IN GENE EXPRESSION AND MUTATIONS IN BLADDER CANCER Kalen Rimar, Joshua Meeks, Sarah Psutka, and Edward Schaeffer Kalen RimarKalen Rimar More articles by this author , Joshua MeeksJoshua Meeks More articles by this author , Sarah PsutkaSarah Psutka More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.195AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES African Americans (AA) with urothelial carcinoma (UC) of the bladder have been shown to have worse cancer-specific (CSS) and overall survival (OS). Though several factors including socioeconomic status, access to care, and advanced stage at presentation have been proposed, the cause of this disparity remains undefined. Our objective was to compare bladder cancer gene expression and mutations between AA and Caucasian patients to assess whether the observed disparities in oncologic outcomes could be explained by associated mutational differences. METHODS Using the Bladder/Urothelial Carcinoma Cancer Genome Atlas (BC-TCGA, Provisional) we compared mutation type, frequency, signature, and gene expression between AA and Caucasian patients. We also compared differentially expressed genes according to race across all TCGA provisional cancer datasets that contained a minimum of 10 AA and 10 Caucasian patients per arm (19 of 33). RESULTS We identified 23 AA and 323 non-AA patients in the UC-TCGA dataset with available whole genome and RNA sequencing. There was no significant difference in the total mutation load between Caucasian and AA (range = 1 to 4472 variants/genome, n = 316, median = 240.5 vs. range = 82 to 562 variants/genome; n = 22, median=225.5, p=0.228). The majority of DNA substitution mutations in both Caucasian and AA patients were C->T, and there was no significant difference in frequency (p=0.33). There were no significant differences in Catalogue of Somatic Mutations in Cancer (COSMIC) signatures between the two groups (p=0.3). There was no significant difference in mutation frequency of known UC driver genes (TP53, MLL4, KDM6A, MLL3, PIK3CA, RB1, EP300, ERBB2) by race. Yet, we were able to identify 14 genes with significant differential expression according to race of which HIST1H2BD, L1TD1, and LRRC37A2 were associated with inferior OS (p<0.005, p=0.03, p=0.02). Notably, analyses of TCGA datasets revealed a conserved panel of genes differentially expressed by race across multiple cancers types involved in cell division and nucleosome function. CONCLUSIONS AA and Caucasians with UC have similar mutation type, frequency, and signature. However several differentially expressed genes within the UC were observed between AA and Caucasians and these differences remain consistent across many cancer types within the TCGA suggesting epigenetic regulation. Some of these gene expression differences may be independent of cancer. Nevertheless, the extent to which this differential gene expression may predispose to variable disease outcomes across race warrants further study. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e52-e53 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Kalen Rimar More articles by this author Joshua Meeks More articles by this author Sarah Psutka More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

How complexity increases in development: An analysis of the spatial-temporal dynamics of Gene expression in Ciona intestinalis

The increase in complexity in an embryo over developmental time is perhaps one of the most intuitive processes of animal development. It is also intuitive that the embryo becomes progressively compartmentalized over time and space. In spite of this intuitiveness, there are no systematic attempts to quantify how this occurs.Here, we present a quantitative analysis of the compartmentalization and spatial complexity of Ciona intestinalis over developmental time by analyzing thousands of gene expression spatial patterns from the ANISEED database. We measure compartmentalization in two ways: as the relative volume of expression of genes and as the disparity in gene expression between body parts. We also use a measure of the curvature of each gene expression pattern in 3D space. These measures show a similar increase over time, with the most dramatic change occurring from the 112-cell stage to the early tailbud stage. Combined, these measures point to a global pattern of increase in complexity in the Ciona embryo. Finally, we cluster the different regions of the embryo depending on their gene expression similarity, within and between stages. Results from this clustering analysis, which partially correspond to known fate maps, provide a global quantitative overview about differentiation and compartmentalization between body parts at each developmental stage.

Epigenetics Meets Radiation Biology as a New Approach in Cancer Treatment

Cancer is a disease that results from both genetic and epigenetic changes. In recent decades, a number of people have investigated the disparities in gene expression resulting from variable DNA methylation alteration and chromatin structure modification in response to the environment. Especially, colon cancer is a great model system for investigating the epigenetic mechanism for aberrant gene expression alteration. Ionizing radiation (IR) could affect a variety of processes within exposed cells and, in particular, cause changes in gene expression, disruption of cell cycle arrest, and apoptotic cell death. Even though there is growing evidence on the importance of epigenetics and biological processes induced by radiation exposure in various cancer types including colon cancer, specific epigenetic alterations induced by radiation at the molecular level are incompletely defined. This review focuses on discussing possible IR-mediated changes of DNA methylation and histone modification in cancer.

Xenobiotic Metabolism and Disposition in Human Lung Cell Models: Comparison with In Vivo Expression Profiles

Numerous lung cell lines are currently used as in vitro models for pharmacological and toxicological studies. However, no exhaustive report about the metabolic capacities of these models in comparison with those of lung tissues is available. In the present study, we used a high-throughput quantitative real-time reverse transcription-polymerase chain reaction strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in 10 commonly used lung cell lines (A549, H292, H358, H460, H727, Calu-1, 16HBE, 1 HAEO, BEAS-2B, and L-132) and four primary cultures of human bronchial epithelial cells. Expression results were then compared with those previously obtained in human nontumoral and tumoral lung tissues. Our results revealed disparities in gene expression between lung cell lines or when comparing lung cell lines with primary cells or lung tissues. Primary cell cultures displayed the highest similarities with bronchial mucosa in terms of transcript profiling and therefore seem to be the most relevant in vitro model for investigating the metabolism and bioactivation of toxicants and drugs in bronchial epithelium. H292 and BEAS-2B cell lines, which exhibited the highest homology in gene expression pattern with primary cells and the lowest number of dysregulated genes compared with nontumoral lung tissues, could be used as surrogates for toxicological and pharmacological studies. Overall, our study should provide references for researchers to choose the most appropriate in vitro model for analyzing the cellular effects of drugs or airborne toxicants on the airway.

Long SAGE analysis of genes differentially expressed in the midgut and silk gland between the sexes of the silkworm Bombyx mori

There are great differences in silk production efficiency and quality between the male and female domestic silkworm (Bombyx mori). Many genes act together but are differentially expressed between the sexes during silk biosynthesis. Two long serial analyses of gene expression (SAGE) libraries were constructed from the midguts and silk glands of both males and females of a sex-limited strain using 5 th instar larvae, yielding in total 96,713 and 98,126 SAGE tags, respectively. Among these tags, 202 were analyzed (p < 0.05 and at least a 2.0-fold change between sexes). Overall, 69 genes were then annotated in detail and 15 tags were annotated with expressed sequence tags (ESTs) based only on the NCBI, SilkDB and long-SAGE libraries. Of these genes, only three could be ascribed to sexual disparity as described by microarray-based expression resources of day three of 5 th instar in Dazao B. mori microarray database (BmMDB). The other 66 genes were considered the SAGE-extracted genes that are differentially expressed between the sexes of the whole 5th instar larvae. Among the 66 genes and 15 tags, genes (and gene families) sex-specific storage-protein 1 gene (Sp1), low molecular mass 30 kDa lipoprotein 19G1 gene (Lp-c19), serine proteinase family [serine protease precursor gene (Spp) and chymotrypsin-like serine protease gene (Ctlp)], Serpins (Spi1 and Spi2) and Ser1, and the tag 1161 (annotated EST No. BY926524), which are involved in protein digestion in the midgut, synthesis of silk and inhibition of protein disintegration in silk gland, were verified by the remarkable disparities in gene expression between the sexes. The established SAGE library would contribute to the further identification of genes related to sexual disparity in silk protein production efficiency. Key words : Bombyx mori , sexes, silk protein production efficiency, long-SAGE, differentially expressed genes.

Differential Expression of Vascular Endothelial Growth Factor, and Angiopoietin 1 and 2 in Functionally Divergent Experimental Rabbit Models of Bladder Hypertrophy

Partial bladder outlet obstruction or ovariectomy with subsequent estrogen replenishment induces bladder hypertrophy in rabbits and yet the functional outcomes of these procedures differ. We investigated whether these models might be distinguished by differential expression of the genes controlling angiogenesis. Groups of male rabbits underwent sham surgery or partial bladder outlet obstruction for 1 or 2 weeks. Groups of females underwent sham surgery, ovariectomy or ovariectomy plus estrogen for 1 or 2 weeks. Bladders from each group were weighed and assayed for the contractile response, smooth muscle content and vascular density. Mucosa and muscle layers were separated and RNA from the fractions was assayed by quantitative real-time polymerase chain reaction to measure the relative expression of vascular endothelial growth factor, and angiopoietin 1 and 2 mRNA. Male bladders with partial outlet obstruction had attributes that typified hypertrophy with a loss of contractile function. Vascular endothelial growth factor expression was up-regulated in the mucosa and muscle layers but the effect was most pronounced in mucosa. Angiopoietin 1 expression was significantly up-regulated in muscle. Female bladders with ovariectomy plus estrogen had attributes that typified bladder hypertrophy with increased contractile function. Vascular endothelial growth factor expression was up-regulated early in mucosa but more highly and consistently increased in muscle. Angiopoietin 1 and 2 expression was not significantly affected. Although these models have similar outcomes with regard to bladder hypertrophy, they have opposite functional outcomes that coincide with compartmental differences in the expression of genes involved in the regulation of angiogenesis. The disparity in gene expression might explain the difference in the functional outcomes.

Quantitative transcriptional neuroanatomy of the rat hippocampus: Evidence for wide‐ranging, pathway‐specific heterogeneity among three principal cell layers

We have used laser-capture microdissection and microarray hybridization to characterize gene expression in the three principal neuron layers of rat hippocampus. Correlative and clustering analyses revealed all three layers to be easily differentiated from one another based on gene expression profile alone. A greater disparity in gene expression exists between dentate granule and pyramidal cell layers, reflecting phenotypic and ontological differences between those cell populations. Remarkably, the level of more than 45% of expressed transcripts was significantly different among the three neuron populations, with more than a third of those (>1,000 transcripts) being at least twofold different between layers. Even CA1 and CA3 pyramidal cell layers were dramatically different on a transcriptional level with a separate analysis indicating that nearly 20% of transcripts are differentially expressed between them. Only a small number of transcripts were specific for a given hippocampal cell layer, suggesting that functional differences are more likely secondary to wide-ranging expression differences of modest magnitude rather than very large disparities in a few genes. Categorical analysis of transcript abundance revealed concerted differences in gene expression among the three cell layers referable to specific cellular pathways. For instance, transcripts encoding proteins involved in glucose metabolism are most highly expressed in the CA3 pyramidal layer, which may reflect an underlying greater metabolic rate of these neurons and partially explain their exquisite vulnerability to seizure-induced damage. Conversely, transcripts related to MAP kinase signaling pathways and transcriptional regulator activity are prominent in the dentate granule cell layer, which could contribute to its resistance to damage following seizure activity by positioning these neurons to respond to external stimuli by altering transcription. Taken together, these data suggest that unique physiological characteristics of major cell layers, such as neuronal activity, neuronal plasticity, and vulnerability to neurodegeneration, are reflected in substantial transcriptional heterogeneity within the hippocampus.

Cancer Susceptibility: Epigenetic Manifestation of Environmental Exposures

Cancer is a disease that results from both genetic and epigenetic changes. Discordant phenotypes and varying incidences of complex diseases such as cancer in monozygotic twins as well as genetically identical laboratory animals have long been attributed to differences in environmental exposures. Accumulating evidence indicates, however, that disparities in gene expression resulting from variable modifications in DNA methylation and chromatin structure in response to the environment also play a role in differential susceptibility to disease. Despite a growing consensus on the importance of epigenetics in the etiology of chronic human diseases, the genes most prone to epigenetic dysregulation are incompletely defined. Moreover, neither the environmental agents most strongly affecting the epigenome nor the critical windows of vulnerability to environmentally induced epigenetic alterations are adequately characterized. These major deficits in knowledge markedly impair our ability to understand fully the etiology of cancer and the importance of the epigenome in diagnosing and preventing this devastating disease.