Examination of Apoptosis Signaling in Pancreatic Cancer by Computational Signal Transduction Analysis

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction. METHODOLOGY/PRINCIPAL FINDINGS: Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway. CONCLUSIONS/SIGNIFICANCE: Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC

Ectomycorrhizal Specificity Patterns in a Mixed Pinus contorta and Picea engelmannii Forest in Yellowstone National Park

We used molecular genetic methods to test two hypotheses, (i) that host plant specificity among ectomycorrhizal fungi would be common in a closed-canopy, mixed Pinus contorta-Picea engelmannii forest in Yellowstone National Park and (ii) that specificity would be more common in the early successional tree species, P. contorta, than in the invader, P. engelmannii. We identified 28 ectomycorrhizal fungal species collected from 27 soil cores. The proportion of P. engelmannii to P. contorta ectomycorrhizae was nearly equal (52 and 48%, respectively). Of the 28 fungal species, 18 composed greater than 95% of the fungal community. No species was associated exclusively with P. contorta, but four species, each found in only one core, and one species found in two cores were associated exclusively with P. engelmannii. These fungi composed less than 5% of the total ectomycorrhizae. Thus, neither hypothesis was supported, and hypothesized benefits of ectomycorrhizal specificity to both trees and fungi probably do not exist in this system

Western gall rust - A threat to Pinus radiata in New Zealand

Western gall rust (Peridermium harknessii J. P. Moore (syn. Endocronartium harknessii (J. P. Moore) Y. Hiratsuka) is potentially a serious threat to exotic Pinus radiata D. Don plantations of New Zealand although the pathogen has not been recorded here. Mechanisms that may have prevented invasion of the pathogen include geographic isolation, biological characteristics of the fungus, stand management, and regulatory mechanisms affecting transport and establishment. Major factors may include a low probability of importation of infected seedlings, unlikely spore transport in the atmosphere across the tropics, and asynchrony of rust sporulation and pine susceptibility in North America and New Zealand. The outbreak or "wave year" phenomenon in the native range of western gall rust demonstrates that both biological and microclimatic conditions must be suitable for establishment to occur. We conclude that the probability of invasion of New Zealand by western gall rust is very low; however, if the pathogen were to become established in New Zealand, the long-term effects may be large

Landscape Biology of Western White Pine: Implications for Conservation of a Widely-Distributed Five-Needle Pine at Its Southern Range Limit

Throughout much of the range of western white pine, Pinus monticola Dougl., timber harvesting, fire exclusion and the presence of Cronartium ribicola J. C. Fisch., the white pine blister rust (WPBR) pathogen, have led to negative population and genetic consequences. To address these interactions, we examined population dynamics and genetic diversity in 10 populations of western white pine in upper montane forests of the Lake Tahoe Basin. We documented negative population trends for three of the 10 populations. These populations exhibited low estimated growth rates (λ), moderate to high incidences of WPBR and mountain pine beetle (MPB), and high levels of mortality. In contrast, seven populations appear to be stable (λ ≥ 1.0), with low to moderate disease and insect incidence, and evidence for genetic resistance to WPBR. Genetic diversity (HE) for a set of 160 single nucleotide polymorphisms was in the range of 0.245–0.272 across populations, and population-specific estimates of FST ranged from 0.0062 to 0.0244. Allele frequency of the Cr2 gene, which confers complete resistance to C. ribicola in western white pine, was low, averaging 0.009 for all populations sampled. However, a low frequency of pollen receptors (i.e., susceptible maternal parents pollinated by a local resistant parent) was found in nine of 10 populations. A moderate and negative relationship was found between the frequency of pollen receptors in a population and the incidence of WPBR (r2 = 0.32). In the context of an introduced pathogen, climate driven outbreaks of MPB, fire exclusion, and prolonged drought, conservation and management strategies are warranted for this species in the Lake Tahoe Basin and likely other locations in California. These strategies include gene conservation of western white pine, WPBR resistance screening, and forest restoration treatments

Comparative Transcriptomics Among Four White Pine Species.

Conifers are the dominant plant species throughout the high latitude boreal forests as well as some lower latitude temperate forests of North America, Europe, and Asia. As such, they play an integral economic and ecological role across much of the world. This study focused on the characterization of needle transcriptomes from four ecologically important and understudied North American white pines within the Pinus subgenus Strobus The populations of many Strobus species are challenged by native and introduced pathogens, native insects, and abiotic factors. RNA from the needles of western white pine (Pinus monticola), limber pine (Pinus flexilis), whitebark pine (Pinus albicaulis), and sugar pine (Pinus lambertiana) was sampled, Illumina short read sequenced, and de novo assembled. The assembled transcripts and their subsequent structural and functional annotations were processed through custom pipelines to contend with the challenges of non-model organism transcriptome validation. Orthologous gene family analysis of over 58,000 translated transcripts, implemented through Tribe-MCL, estimated the shared and unique gene space among the four species. This revealed 2025 conserved gene families, of which 408 were aligned to estimate levels of divergence and reveal patterns of selection. Specific candidate genes previously associated with drought tolerance and white pine blister rust resistance in conifers were investigated

Comparative Transcriptomics Among Four White Pine Species

Conifers are the dominant plant species throughout the high latitude boreal forests as well as some lower latitude temperate forests of North America, Europe, and Asia. As such, they play an integral economic and ecological role across much of the world. This study focused on the characterization of needle transcriptomes from four ecologically important and understudied North American white pines within the Pinus subgenus Strobus. The populations of many Strobus species are challenged by native and introduced pathogens, native insects, and abiotic factors. RNA from the needles of western white pine (Pinus monticola), limber pine (Pinus flexilis), whitebark pine (Pinus albicaulis), and sugar pine (Pinus lambertiana) was sampled, Illumina short read sequenced, and de novo assembled. The assembled transcripts and their subsequent structural and functional annotations were processed through custom pipelines to contend with the challenges of non-model organism transcriptome validation. Orthologous gene family analysis of over 58,000 translated transcripts, implemented through Tribe-MCL, estimated the shared and unique gene space among the four species. This revealed 2025 conserved gene families, of which 408 were aligned to estimate levels of divergence and reveal patterns of selection. Specific candidate genes previously associated with drought tolerance and white pine blister rust resistance in conifers were investigated