Avian pathogenic Escherichia coli strains frequently cause extra-intestinal infections and are responsible for significant economic losses in the poultry industry worldwide. APEC isolates are closely related to human extraintestinal pathogenic E.coli strains and may also act as pathogens for humans. In this work, three type VI secretion systems were deleted to analyze which pathogenicity characteristics would change in the mutants, compared to wild type strain (SEPT 362).
The type VI secretion system plays a role in type 1 fimbria expression and pathogenesis of an avian pathogenic Escherichia coli strain.
No sample metadata fields
View SamplesThere is cardiac dysfunction in male eNOS (-/-) with age and 50% mortality at 21M. It was of interest to investigate the gene expression profile of aged eNOS (-/-) male in comparison to (+/+) in order to explore the genetic markers and molecular mechanisms leading to heart failure. RNA was extracted from the left ventricle from male (-/-) (n=3) and (+/+) (n=4) at the age of 21M.
Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype.
No sample metadata fields
View SamplesBackground: Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO). The two most predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increase adhesion to intestinal cells and increase the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. Results: HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source. Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both down-regulated genes in Caco-2 cells associated with chemokine activity. Conclusion: The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics. Overall design: CACO-2 cells incubated with Bifidobacterium longum subsp. infantis grown on (1) glucose, (2) lactose, or (3) human milk oligosaccharides. All experiments were run in triplicate.
Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells.
No sample metadata fields
View SamplesBackground: Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO). The two most predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increase adhesion to intestinal cells and increase the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. Results: HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source. Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both down-regulated genes in Caco-2 cells associated with chemokine activity. Conclusion: The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics. Overall design: CACO-2 cells incubated with Bifidobacterium breve grown on (1) glucose, (2) lactose, or (3) human milk oligosaccharides. All experiments were run in triplicate.
Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells.
No sample metadata fields
View SamplesTwo sets of wheat lines near-isogenic to Lr34 were used to compare gene expression profiles of wheat: 1. with and without Lr34 gene; 2. rust and mock inoculation; 3. distal and basal portion of the flag leaves. The two sets of wheat near-isogenic lines were used to subtract genetic background variations and to enrich Lr34-regulated gene expression profiles. The study is aimed to better understand the mechanisms of the well-known durable leaf rust resistance gene, Lr34, mediated resistance at the transcriptome level.
Gene expression patterns in near isogenic lines for wheat rust resistance gene lr34/yr18.
No sample metadata fields
View SamplesCurrent human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat.
Sperm mRNA transcripts are indicators of sub-chronic low dose testicular injury in the Fischer 344 rat.
Specimen part, Treatment
View SamplesAlthough mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression.
Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative DNA methylation and gene expression analyses identify DNA packaging and epigenetic regulatory genes associated with low motility sperm.
No sample metadata fields
View SamplesLymphangioleiomyomatosis (LAM) is characterized by cystic lung destruction caused by smooth, muscle-like LAM cells which have mutations in the tumor suppressor genes Tuberous Sclerosis Complex (TSC) 1 or 2, and the capacity to metastasize. Since chemokines and their receptors function in chemotaxis of metastatic cells, we hypothesized that LAM cells may be recruited by chemokine(s) in the lung. Quantification of 25 chemokines in bronchoalveolar lavage fluid from LAM patients and healthy volunteers revealed that concentrations of MCP-1/CCL2, GROa/CXCL1 and ENA-78/CXCL5 were significantly higher in samples from LAM patients than healthy volunteers. In this transcript analysis, expression of chemokine and chemokine receptor mRNA in LAM cells differed from those in melanoma and smooth muscle cells. Subsequent immunohistochemistry of lung sections from 30 LAM patients confirmed protein expression of chemokines and these receptors varied among LAM patient and differed from that seen in breast cancer and melanoma cells. . In vitro, MCP-1/CCL2 induced selective migration of cells showing loss of heterozygosity of TSC2 from a heterogeneous populations of cells grown from explanted LAM lungs. In addition, the frequencies of single-nucleotide polymorphisms in the MCP-1 gene promoter region differed significantly in LAM patients and healthy volunteers (p=0.018), and one polymorphism was associated significantly more frequently with the decline of lung function. These observations are consistent with the notion that chemokines such as MCP-1 may serve to specify site of LAM cell metastasis.
Chemokine-enhanced chemotaxis of lymphangioleiomyomatosis cells with mutations in the tumor suppressor TSC2 gene.
Sex, Specimen part
View SamplesRett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. RTT is characterized by having apparently normal development until 6-18 months, when a progressive decline in motor and language functions begins and breathing abnormalities and seizures present. Despite intense research, the molecular targets of MeCP2 and their contribution to the disease are unknown. Here we present the first comprehensive and comparative transcriptomic and proteomic analysis in a RTT mouse model. Examining whole cortex tissue in symptomatic males (Mecp2Jae/y) and wild-type littermates, we have identified 391 genes and 465 proteins considered to be significantly altered. We observed an overall poor correlation between global gene and protein expression (Pearson correlation 0.12), yet 35 hits were common to both data sets, with 12 hits not described elsewhere. These 35 hits indicate disrupted cellular metabolism, calcium signaling, protein stability, DNA binding and cytoskeletal cell structure in the RTT cortex. Pathway analysis in both data sets identified biological pathways ubiquitous to multiple cell types as well as cell type specific pathways, underscoring the contributions of multiple central nervous system (CNS) cell populations to the disease pathogenesis. These findings prompted us to compare identified 'hits' to a publicly available database containing CNS cell type specific gene expression. This indicated approximately 32% of differentially expressed (DE) genes and 16% proteins were highly enriched in unique CNS cell types, while the remaining DE genes and proteins were ubiquitously expressed and not ascribable to any unique cell population. Our comparative transcriptome and proteome analysis in the cortex of RTT mice supports previous works indicating widespread CNS dysfunction. Overall design: Wild-type (WT) males were bred with heterozygous Mecp2tm1.1Jae/+ (Jaenisch) female mice. The whole cortex of mutant male mice (Mecp2Jae/y) along with WT littermates were collected after postnatal day 60 (P60+). An n of 4 biological replicates per genotype were used, with WT animals serving as controls. For RNA-Sequencing, 2 technical replicates were run per biological replicate.
RNA sequencing and proteomics approaches reveal novel deficits in the cortex of <i>Mecp2</i>-deficient mice, a model for Rett syndrome.
Sex, Specimen part, Cell line, Subject
View Samples