Seasonal succession of pollinator floral resources in four types of grasslands

Pollinators are declining globally, and this decline in ecosystem services threatens the stability of agricultural and natural systems. Pollinators depend on a diversity of floral resources that are primarily found in uncultivated areas of agro‐ecosystems such as grasslands. Seasonal succession (the seasonal changes that occur in community composition and structure) of floral resources is an essential consideration for pollinator conservation within agro‐ecosystems. Different types of grasslands common within agricultural landscapes could be expected to differ in their seasonal succession of floral resources. Here we investigated how different types of grasslands important for pollinator conservation in the tallgrass prairie ecoregion (remnant prairies, reconstructed prairies, conservation grazed cattle pastures, and old fields) differ in their seasonal succession of floral resources by sampling the plant community every two weeks from 3 May through 4 October 2013. We found remnant prairies had greater richness of inflorescences when summed over the growing season, and that remnants were least similar to the other grassland types in terms of composition. Reconstructed prairies had high richness of inflorescences and exhibited the most similarity in composition to remnant prairies only during the middle of the growing season. Conservation grazed cattle pastures had more periods where turnover in composition from one survey to the next was low, indicated by the coefficient of variation in turnover throughout the season. Old fields had the lowest richness of inflorescences and were significantly different from reconstructed and remnant prairies

Assessing Alternative Futures of Agriculture in Iowa, U.S.A.

The contributions of current agricultural practices to environmental degradation and the social problems facing agricultual regions are well known. However, landscape-scale alternatives to current trends have not been fully explored nor their potential impacts quantified. To address this research need, our interdisciplinary team designed three alternative future scenarios for two watersheds in Iowa, USA, and used spatially-explicit models to evaluate the potential consequences of changes in farmland management. This paper summarizes and integrates the results of this interdisciplinary research project into an assessment of the designed alternatives intended to improve our understanding of landscape ecology in agricultural ecosystems and to inform agricultural policy. Scenario futures were digitized into a Geographic Information System (GIS), visualized with maps and simulated images, and evaluated for multiple endpoints to assess impacts of land use change on water quality, social and economic goals, and native flora and fauna. The Biodiversity scenario, targeting restoration of indigenous biodiversity, ranked higher than the current landscape for all endpoints (biodiversity, water quality, farmer preference, and profitability). The Biodiversity scenario ranked higher than the Production scenario (which focused on profitable agricultural production) in all endpoints but profitability, for which the two scenarios scored similarly, and also ranked higher than the Water Quality scenario in all enpoints except water quality. The Water Quality scenario, which targeted improvement in water quality, ranked highest of all landscapes in potential water quality and higher than the current landsape and the Production scenario in all but profitability. Our results indicate that innovative agricultural practices targeting environmental improvements may be acceptable to farmers and could substantially reduce the environmental impacts of agriculture in this region.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49340/1/LE04Santel.pd

Genomic predictors of patterns of progression in glioblastoma and possible influences on radiation field design

We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma (GBM). Between August 2000 and May 2010, 41 patients with GBM and gene expression and methylation data available were treated with radiotherapy with or without concurrent temozolomide. Location of disease progression was categorized as within the high dose (60 Gy) or low dose (46 Gy) volume. Samples were grouped into previously described TCGA genomic groupings: Mesenchymal (m), classical (c), proneural (pn), and neural (n); and were also classified by MGMT-Methylation status and G-Cimp methylation phenotype. Genomic groupings and methylation status were investigated as a possible predictor of disease progression in the high dose region, progression in the low dose region, and time to progression. Based on TCGA category there was no difference in OS (p = 0.26), 60 Gy progression (PN: 71 %, N: 60 %, M: 89 %, C: 83 %, p = 0.19), 46 Gy progression (PN: 57 %, N: 40 %, M: 61 %, C: 50 %, p = 0.8) or time to progression (PN: 9 months, N:15 months, M: 9 months, C: 7 months, p = 0.58). MGMT methylation predicted for improved OS (median 25 vs. 13 months, p = 0.01), improved DFS (median 13 vs. 8 months, p = 0.007) and decreased 60 Gy (p = 0.003) and 46 Gy (p = 0.006) progression. There was a cohort of MGMT methylated patients with late marginal disease progression (4/22 patients, 18 %). TCGA groups demonstrated no difference in survival or progression patterns. MGMT methylation predicted for a statistically significant decrease in in-field and marginal disease progression. There was a cohort of MGMT methylated patients with late marginal progression. Validations of these findings would have implications that could affect radiation field size

Assessing alternative futures for agriculture in Iowa, U.S.A.

The contributions of current agricultural practices to environmental degradation and the social problems facing agricultural regions are well known. However, landscape-scale alternatives to current trends have not been fully explored nor their potential impacts quantified. To address this research need, our interdisciplinary team designed three alternative future scenarios for two watersheds in Iowa, USA, and used spatially-explicit models to evaluate the potential consequences of changes in farmland management. This paper summarizes and integrates the results of this interdisciplinary research project into an assessment of the designed alternatives intended to improve our understanding of landscape ecology in agricultural ecosystems and to inform agricultural policy. Scenario futures were digitized into a Geographic Information System (GIS), visualized with maps and simulated images, and evaluated for multiple endpoints to assess impacts of land use change on water quality, social and economic goals, and native flora and fauna. The Biodiversity scenario, targeting restoration of indigenous biodiversity, ranked higher than the current landscape for all endpoints (biodiversity, water quality, farmer preference, and profitability). The Biodiversity scenario ranked higher than the Production scenario (which focused on profitable agricultural production) in all endpoints but profitability, for which the two scenarios scored similarly, and also ranked higher than the Water Quality scenario in all endpoints except water quality. The Water Quality scenario, which targeted improvement in water quality, ranked highest of all landscapes in potential water quality and higher than the current landscape and the Production scenario in all but profitability. Our results indicate that innovative agricultural practices targeting environmental improvements may be acceptable to farmers and could substantially reduce the environmental impacts of agriculture in this region.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43158/1/10980_2004_Article_5253979.pd

Gene expression analysis after receptor tyrosine kinase activation reveals new potential melanoma proteins

<p>Abstract</p> <p>Background</p> <p>Melanoma is an aggressive tumor with increasing incidence. To develop accurate prognostic markers and targeted therapies, changes leading to malignant transformation of melanocytes need to be understood. In the <it>Xiphophorus </it>melanoma model system, a mutated version of the EGF receptor Xmrk (<it>Xiphophorus </it>melanoma receptor kinase) triggers melanomagenesis. Cellular events downstream of Xmrk, such as the activation of Akt, Ras, B-Raf or Stat5, were also shown to play a role in human melanomagenesis. This makes the elucidation of Xmrk downstream targets a useful method for identifying processes involved in melanoma formation.</p> <p>Methods</p> <p>Here, we analyzed Xmrk-induced gene expression using a microarray approach. Several highly expressed genes were confirmed by realtime PCR, and pathways responsible for their induction were revealed using small molecule inhibitors. The expression of these genes was also monitored in human melanoma cell lines, and the target gene <it>FOSL1 </it>was knocked down by siRNA. Proliferation and migration of siRNA-treated melanoma cell lines were then investigated.</p> <p>Results</p> <p>Genes with the strongest upregulation after receptor activation were FOS-like antigen 1 (<it>Fosl1</it>), early growth response 1 (<it>Egr1</it>), osteopontin (<it>Opn</it>), insulin-like growth factor binding protein 3 (<it>Igfbp3</it>), dual-specificity phosphatase 4 (<it>Dusp4</it>), and tumor-associated antigen L6 (<it>Taal6</it>). Interestingly, most genes were blocked in presence of a SRC kinase inhibitor. Importantly, we found that <it>FOSL1</it>, <it>OPN</it>, <it>IGFBP3</it>, <it>DUSP4</it>, and <it>TAAL6 </it>also exhibited increased expression levels in human melanoma cell lines compared to human melanocytes. Knockdown of <it>FOSL1 </it>in human melanoma cell lines reduced their proliferation and migration.</p> <p>Conclusion</p> <p>Altogether, the data show that the receptor tyrosine kinase Xmrk is a useful tool in the identification of target genes that are commonly expressed in Xmrk-transgenic melanocytes and melanoma cell lines. The identified molecules constitute new possible molecular players in melanoma development. Specifically, a role of FOSL1 in melanomagenic processes is demonstrated. These data are the basis for future detailed analyses of the investigated target genes.</p

Growth inhibition of non-small cell lung cancer cells by AP-1 blockade using a cJun dominant-negative mutant

cJun, a major constituent of AP-1 transcription factor transducing multiple mitogen growth signals, is frequently overexpressed in non-small cell lung cancers (NSCLCs). The purpose of this study is to determine the effects of AP-1 blockade on the growth of NSCLC cells using a cJun dominant-negative mutant, TAM67. Transiently transfected TAM67 inhibited AP-1 transcriptional activity in NSCLC cell lines, NCI-H1299 (H1299), A549 and NCI-H520 (H520). The colony-forming efficiency of H1299 and A549 was reduced by TAM67, while that of H520 was not. To elucidate the effects of TAM67 on the growth of H1299, we established H1299 clone cells that expressed TAM67 under the control of a doxycycline-inducible promoter. In the H1299 clone cells, the induced TAM67 inhibited anchorage-dependent growth by promoting G1 cell-cycle block, but not by apoptosis. The induced TAM67 decreased the expression of a cell-cycle regulatory protein, cyclin A. TAM67 also inhibited anchorage-independent growth of these cells. Furthermore, TAM67 reduced growth of established xenograft tumours from these cells in nude mice. These results suggest that AP-1 plays an essential role in the growth of at least some of NSCLC cells

DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons

The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5′ CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts—defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)—were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase

Genetic Epidemiology of Glioblastoma Multiforme: Confirmatory and New Findings from Analyses of Human Leukocyte Antigen Alleles and Motifs

Human leukocyte antigen (HLA) class I genes mediate cytotoxic T-lymphocyte responses and natural killer cell function. In a previous study, several HLA-B and HLA-C alleles and haplotypes were positively or negatively associated with the occurrence and prognosis of glioblastoma multiforme (GBM).As an extension of the Upper Midwest Health Study, we have performed HLA genotyping for 149 GBM patients and 149 healthy control subjects from a non-metropolitan population consisting almost exclusively of European Americans. Conditional logistic regression models did not reproduce the association of HLA-B*07 or the B*07-Cw*07 haplotype with GBM. Nonetheless, HLA-A*32, which has previously been shown to predispose GBM patients to a favorable prognosis, was negatively associated with occurrence of GBM (odds ratio=0.41, p=0.04 by univariate analysis). Other alleles (A*29, A*30, A*31 and A*33) within the A19 serology group to which A*32 belongs showed inconsistent trends. Sequencing-based HLA-A genotyping established that A*3201 was the single A*32 allele underlying the observed association. Additional evaluation of HLA-A promoter and exon 1 sequences did not detect any unexpected single nucleotide polymorphisms that could suggest differential allelic expression. Further analyses restricted to female GBM cases and controls revealed a second association with a specific HLA-B sequence motif corresponding to Bw4-80Ile (odds ratio=2.71, p=0.02).HLA-A allelic product encoded by A*3201 is likely to be functionally important to GBM. The novel, sex-specific association will require further confirmation in other representative study populations